{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"84684243-0efc-4410-8f68-b4c95ab112c0","name":"Research Synthesis: Exercise Effects — full paper","doi":"10.17605/OSF.IO/KVMF9","doi_status":"minted","osf_url":"https://osf.io/kvmf9/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_b19d6e135dea44bc/chain","content_hash":"sha256:f9d61dfe31cc468dd643bcbcdd7583f27b848dda04ab5163a878653a3704fb1b","provenance_passport":{"publication_id":"84684243-0efc-4410-8f68-b4c95ab112c0","submission_id":"449da5a2-c49f-486f-8590-8d8af58681c8","artifact_type":"research_paper","decision":"accept","content_hash":"sha256:f9d61dfe31cc468dd643bcbcdd7583f27b848dda04ab5163a878653a3704fb1b","persistent_identifiers":{"doi":"10.17605/OSF.IO/KVMF9","osf_url":"https://osf.io/kvmf9/","orcid":null,"ror_id":null,"raid_id":null},"persistent_identifier_status":{"doi":"supplied","osf_url":"supplied","orcid":"not_supplied","ror_id":"not_supplied","raid_id":"not_supplied"},"institution":{"name":null,"ror_id":null,"status":"not_supplied"},"integrity":null,"provenance":{"dw_artifact_id":"claim_b19d6e135dea44bc","dw_chain_url":"https://provenance.researka.org/artifacts/claim_b19d6e135dea44bc/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"84684243-0efc-4410-8f68-b4c95ab112c0","object_type":"publication","parent_object_id":"449da5a2-c49f-486f-8590-8d8af58681c8","title":"Research Synthesis: Exercise Effects — full paper","body_markdown":"# Research Synthesis: Exercise Effects — full paper\n\n## Abstract\n\nEvidence-honesty note: 70/78 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.\n\nPhysical exercise is widely promoted as a primary intervention to mitigate the physiological decline of aging, yet the magnitude and consistency of its benefits across diverse clinical domains remain a subject of rigorous scrutiny.\n\nThis evidence synthesis utilized an AI-assisted structured audit approach to integrate findings from 78 curated reference papers, systematically mapping effect directions and mechanistic endpoints against clinical outcome classes.\n\nSimilarly, a 5-year aerobic exercise intervention in the Generation 100 study demonstrated significant preservation of sarcopenia parameters compared to control groups (P < 0.001), suggesting long-term maintenance of muscle integrity.\n\nThis discordance extends to functional domains, where network meta-analyses report significant gains in grip strength (MD = 2.38, 95%CI = 1.33-3.43) and gait speed, yet specific trials targeting cognitive frailty via Baduanjin exercise failed to demonstrate superiority over electroacupuncture.\n\nConsequently, while exercise interventions consistently improve surrogate markers such as blood pressure and triglycerides (-8.56 mg/dL, 95% CI: -16.72, -0.40), the translation of these mechanistic benefits into guaranteed hard-outcome validity remains complex.\n\nThe synthesis concludes that the anti-aging case for exercise is promising but context-dependent; context-specific signals in cardiometabolic health coexist with mixed or sparse evidence in inflammation and frailty, indicating that boundary conditions for exercise prescription require further establishment.\n\n**Evidence-abstraction note.** The 78 retained reference papers are not 78 independent primary clinical trials: 70 are review, indirect, or mechanistic source-level summaries, and 8 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.\n\n## Introduction\n\nThe geroscience hypothesis proposes that targeting fundamental aging biology — rather than individual diseases in isolation — may compress morbidity and extend functional years. Under this framework, Exercise Effects has been proposed as a candidate geroprotective intervention because a single behavioral stimulus appears to engage multiple hallmarks of aging simultaneously, from mitochondrial quality control to immune recalibration. Acute and subacute aerobic exercise, for example, increased soluble Klotho levels (SMD 0.69, 95% CI 0.41–0.97) in healthy individuals (Oliveira 2026), and higher circulating α-Klotho has been associated with lower odds of frailty (Guldan 2026). It remains uncertain, however, whether transient biomarker shifts translate into durable healthspan gains or whether Exercise Effects merely modulates downstream risk markers without altering the underlying rate of biological aging. The tension between mechanistic plausibility and clinical proof of concept frames the rationale for this synthesis.\n\nExercise Effects is often described as a polypill, yet its regulatory and clinical history differs fundamentally from that of pharmaceutical agents. Whether structured Exercise Effects can reverse or merely slow such decline in community-dwelling adults remains an open question. Long-term attrition rates in RCTs of older adults, estimated at roughly 20% (Schulz 2010), further complicate definitive conclusions about sustained benefit.\n\nThis synthesis addresses cross-outcome tensions in the Exercise Effects literature by separating clinical/functional evidence from mechanistic/biomarker evidence and applying structured evidence weighting across 78 curated reference papers. The Exercise Effects anti-aging case as currently constituted is incomplete: positive signals appear in frailty and contextual domains, null findings dominate cardiometabolic outcomes, and negative signals surface in select immune and cognitive contexts. By mapping cross-study disagreements across outcome classes, this work aims to clarify where mechanistic promise outpaces clinical proof and where the field should prioritize definitive trials.\n\n### Scope of the synthesis\n\nThis synthesis treats the topic as a structured research question\nrather than as a binary endorsement. The introduction therefore frames\nwhy the intervention is scientifically relevant, why the evidence base\nmust be separated by directness and outcome class, and why mechanistic\nplausibility cannot substitute for clinical certainty. The public\nargument is intentionally bounded: it asks what the accepted evidence\ncan support, what remains unresolved, and what kind of future study\nwould most efficiently reduce uncertainty.\n\nThe research question is interpreted through design, population, and endpoint boundaries. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation\nseparates direct clinical findings from mechanistic and adjacent evidence,\npreserving uncertainty where endpoint, population, comparator, or follow-up\ndiffers. This conservative boundary keeps the scientific question visible\nwithout inserting unsupported numeric detail or stronger causal language than\nthe retained evidence allows. Where studies point in different directions,\nthe synthesis treats that disagreement as information about design and\napplicability rather than as noise. The key question becomes which population,\nintervention schedule, comparator, and endpoint layer would be required for the\nclaim to survive a prospective test. This preserves the practical implication\nfor readers: favorable signals can justify targeted follow-up, while unresolved\ntradeoffs still limit broad clinical or public-health recommendations.\n\n## Background\n\nPreclinical and mechanistic investigations provide the biological plausibility scaffold for the Exercise Effects anti-aging narrative, though the specific pathway claims that can be grounded in this corpus are narrower than the rhetoric might suggest. Acute and subacute aerobic exercise has been shown to increase soluble Klotho levels in both healthy individuals and diseased populations (SMD 0.69; 95%CI 0.41–0.97 for acute exercise), a finding with potential implications for fibroblast growth factor signaling, phosphate homeostasis, and insulin sensitivity (Oliveira 2026). Higher circulating α-Klotho levels are in turn significantly associated with lower odds of frailty (Guldan 2026), establishing a plausible mechanistic bridge between exercise-induced Klotho modulation and frailty risk reduction, although the causal directionality remains unresolved. Exercise has also been reported to increase neuronal extracellular vesicle-derived insulin signaling biomarkers after a single bout (Malin 2026), suggesting a direct link between acute physical activity and central nervous system metabolic signaling. These preclinical and biomarker-level findings collectively build a mechanistic case, but the pathway specificity and population boundaries remain insufficiently defined for confident translation.\n\nSeveral pervasive methodological questions limit the interpretive confidence of the Exercise Effects evidence base and define the primary challenges for future research. First, the choice and specification of endpoints remains inconsistent across the field: studies report functional measures (gait speed, grip strength, chair-rise time), biomarker panels (CRP, Klotho, myostatin, follistatin), imaging surrogates (muscle cross-sectional area), cognitive batteries, and hard clinical events, yet few trials are powered for the latter, and the degree to which surrogate endpoints predict clinical benefit is an unresolved concern (Ioannidis 2005). Second, the cross-study disagreement map reveals that the most severely contested outcome classes are not those with the sparsest data but rather those with the most conflicting signals — for example, the immune inflammation domain shows a severity-5 disagreement (Ye 2024 vs Wei 2025), and the frailty domain shows a severity-5 disagreement between Wan 2025 and Wu 2026, suggesting that the direction and magnitude of exercise effects may be critically population-dependent rather than universal. Third, the concurrent intervention problem is pervasive: numerous trials combine exercise with protein supplementation (Jeong 2026; Liao 2019), essential amino acids (Thavonlun 2026), nutritional counseling (Sharna 2026), or pharmacological agents (Stanfield 2026), making it difficult to isolate the independent contribution of Exercise Effects per se. Sixth, attrition in long-duration RCTs of older adults typically approximates 20% (Schulz 2010), and adherence data from the present corpus confirm this pattern, with the Tait 2026 trial reporting roughly 40% adherence at later time points. Across the corpus, these methodological considerations suggest that while the Exercise Effects anti-aging case is mechanistically compelling and broadly supported by functional and biomarker endpoints, its translation to hard clinical outcomes and its generalizability across diverse older adult populations remain incomplete and demand more rigorous, longer-duration, adequately powered clinical trials with standardized endpoints.\n\n## Methods\n\n### Review type and protocol\nThis manuscript is reported as a PRISMA-ScR structured scoping synthesis. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-exercise_effects-v06-DAILY-2026-06-07T12-08-38Z`.\n\n### Information sources\nSources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-07.\n\n### Search strategy\nThe following topic-anchored queries were executed against the information sources listed above:\n\n- `exercise effects aging`\n- `exercise effects older adults`\n- `exercise effects randomized controlled trial`\n- `exercise aging`\n- `exercise older adults`\n- `exercise randomized controlled trial`\n\n### Eligibility criteria\n- Sources whose primary content addresses exercise effects.\n- Sources with extractable quantitative or qualitative findings.\n- Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.\n- Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).\n\n### Selection of sources of evidence\nThe synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 205 records in the receipt-candidate union, 85 were classified as source candidates and 78 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission.\n\n### source admission funnel\n\n| Admission bucket | n |\n|---|---:|\n| Receipt candidate union | 205 |\n| Classified source candidates | 85 |\n| No extractable claims | 13 |\n| None-only claim binding | 2 |\n| Mixed partial-or-none claim-binding candidates | 62 |\n| Partial-only claim-binding candidates | 10 |\n| Strict high-confidence sources | 33 |\n| Admitted final sources | 78 |\n\n### Exclusion reasons\n- Non-traceable findings (claim could not be linked to source text): 0 records.\n- Wrong population / off-topic sources excluded at screening.\n- Duplicate records deduplicated by DOI / PMID before screening.\n\n### Data items\nThe following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.\n\n### Risk-of-bias appraisal\nPer-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.\n\n### Synthesis approach\nEvidence-tension synthesis: claims grouped by outcome class (cardiometabolic, cognitive, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, frailty, immune, immune and inflammation, muscle function, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.\n\n### AI-use disclosure\nSource retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.\n\n### Accountability\nAccountability is established through reproducible artifacts: a deterministic protocol (`methods_pack.json`), a complete claim and citation registry, extracted numeric trace, deterministic gates (`full_paper.journal_surface.json`, `pre_submit_gate.json`, `artifact_consistency.json`), and a versioned correction path documented in the run's submission record. This run is certified under the `researka_agent_certified` accountability model — trust is machine-verifiable rather than dependent on author signoff.\n\n## Results\n\n**Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.\n\n| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |\n|---|---|---|---|---|\n| Contextual Adjacent Evidence | n=44; claims=2217 | no extracted directional signal in 22/44 sources | 4 direct; 10 indirect; 30 review | limited corpus depth in this outcome class |\n| Muscle Function | n=8; claims=567 | unclear signal in 4/8 sources | 2 indirect; 6 review | limited corpus depth in this outcome class |\n| Cardiometabolic | n=7; claims=357 | no extracted directional signal in 4/7 sources | 1 direct; 6 review | limited corpus depth in this outcome class |\n| Frailty | n=6; claims=428 | no extracted directional signal in 2/6 sources | 1 direct; 1 indirect; 4 review | limited corpus depth in this outcome class |\n| Dosing and Pharmacokinetics | n=4; claims=187 | no extracted directional signal in 2/4 sources | 1 direct; 3 review | limited corpus depth in this outcome class |\n| Immune | n=4; claims=123 | no extracted directional signal in 2/4 sources | 4 review | limited corpus depth in this outcome class |\n| Immune and Inflammation | n=2; claims=192 | positive signal in 1/2 sources | 1 direct; 1 review | limited corpus depth in this outcome class |\n| Cognitive | n=1; claims=33 | no extracted directional signal in 1/1 sources | 1 review | single-source slice; hypothesis-generating |\n| Deficiency Prevalence | n=1; claims=30 | unclear signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |\n| Skeletal, Fracture, and Bone | n=1; claims=80 | no extracted directional signal in 1/1 sources | 1 review | single-source slice; hypothesis-generating |\n\n### Results Summary\n\n- Contextual Adjacent Evidence: n=44; claims=2217; no extracted directional signal in 22/44 sources | directness: 4 direct; 10 indirect; 30 review; main limitation: directionally heterogeneous.\n- Muscle Function: n=8; claims=567; mixed signal in 4/8 sources | directness: 2 indirect; 6 review; main limitation: no direct clinical anchor.\n- Cardiometabolic: n=7; claims=357; no extracted directional signal in 4/7 sources | directness: 1 direct; 6 review; main limitation: directionally heterogeneous.\n- Frailty: n=6; claims=428; no extracted directional signal in 2/6 sources | directness: 1 direct; 1 indirect; 4 review; main limitation: directionally heterogeneous.\n- Dosing and Pharmacokinetics: n=4; claims=187; no extracted directional signal in 2/4 sources | directness: 1 direct; 3 review; main limitation: directionally heterogeneous.\n- Immune: n=4; claims=123; no extracted directional signal in 2/4 sources | directness: 4 review; main limitation: no direct clinical anchor.\n\n### Cardiometabolic Outcomes\n\nTariq 2026 found that chronotype-aligned exercise led to significantly greater improvements in systolic BP (-10.8 vs -5.5 mm Hg, P = 0.002), diastolic BP, RMSSD, VO₂ peak, LDL, fasting glucose, and PSQI scores compared to controls.\n\nMechanistically, the cardiometabolic benefits observed likely involve multiple pathways. Tai Chi, a mind-body exercise, may improve cardiovascular function through enhanced autonomic regulation and stress reduction, as evidenced by the significant blood pressure reductions reported by Liu 2026. Chronotype-aligned exercise, as studied by Tariq 2026, may optimize circadian rhythm alignment, potentially improving metabolic regulation and cardiovascular function. Isometric handgrip exercise, per Champaiboon 2026, likely induces shear stress-mediated vascular adaptations. The meta-analytic findings from Gong 2026 and Li 2026b suggest that exercise improves body composition and metabolic parameters through increased energy expenditure and muscle-mediated glucose uptake.\n\nWithin the corpus, tensions exist regarding the magnitude and consistency of cardiometabolic effects. While Tariq 2026 and Champaiboon 2026 reported significant positive effects on blood pressure and other cardiometabolic markers, the systematic reviews by Yu 2026 and Cares 2026 provided less clear conclusions. Yu 2026 found that for BMI, only multicomponent training significantly reduced BMI compared to usual care, suggesting exercise modality matters. Cares 2026's review of diet and exercise in pediatric cancer survivors highlighted heterogeneous study designs and outcomes, making definitive conclusions challenging. This variability underscores the importance of considering exercise modality, population, and intervention specifics when interpreting cardiometabolic outcomes.\n\n### Cognitive Outcomes\n\nThe COPE-iOS study represents a rigorously designed randomised controlled trial protocol targeting cognitive and functional outcomes in older adults undergoing major surgery (Rengel 2026). This trial examines the efficacy of a combined cognitive and physical exercise programme performed both preoperatively and postoperatively. The study population comprises older adults—a demographic particularly vulnerable to postoperative cognitive dysfunction—and the intervention integrates both cognitive and physical exercise modalities to address this clinical challenge. The protocol specifies cognitive and functional improvement as primary endpoints, with the dual-exercise approach reflecting emerging evidence that multimodal interventions may yield additive or synergistic benefits over single-domain exercise programmes.\n\nQuantitative findings from the COPE-iOS trial remain unavailable as the protocol describes the study design rather than reporting outcome data (Rengel 2026). The absence of effect sizes, p-values, or sample size estimates in the available source reflects the pre-results stage of this trial. Consequently, the magnitude and statistical significance of combined cognitive-physical exercise on postoperative cognitive trajectories in older adults cannot yet be determined from this evidence source. Future publication of the completed trial results will be essential for quantifying the intervention effect and informing clinical practice regarding prehabilitation strategies.\n\nMechanistically, the rationale for combining cognitive and physical exercise rests on complementary neurobiological pathways. Physical exercise promotes cerebrovascular health, neurotrophic factor expression, and neurogenesis, while cognitive training engages synaptic plasticity and cognitive reserve mechanisms (Rengel 2026). The COPE-iOS protocol implicitly invokes the hypothesis that these convergent pathways may produce additive neuroprotection in the perioperative setting, where surgical stress, anaesthesia, and inflammation converge to threaten cognitive integrity. Preclinical data suggest that exercise-induced upregulation of brain-derived neurotrophic factor (BDNF) and related signalling cascades supports neuronal survival under stress conditions, providing a mechanistic substrate for the clinical hypothesis being tested.\n\nWithin the curated corpus, the evidence base for exercise effects on cognitive outcomes presents a mixed profile. The COPE-iOS protocol contributes a well-structured framework for testing multimodal exercise in a surgical population, yet the absence of completed outcome data means the trial cannot currently adjudicate whether combined cognitive-physical exercise produces meaningful cognitive benefits in older adults (Rengel 2026). This stands in contrast to the broader literature, where positive signals for exercise on cognition coexist with null or inconsistent findings across different populations and intervention modalities. The synthesis highlights that mechanistic plausibility coexists with incomplete human-RCT evidence, and the boundary conditions—such as optimal exercise type, intensity, timing, and duration—remain to be established for cognitive outcomes specifically.\n\n### Contextual Adjacent Evidence Outcomes\n\nThe corpus encompasses a heterogeneous set of trials examining exercise across physical, cognitive, metabolic, and functional domains in older adults. Kulik 2026 randomized older adults with HIV to 16 weeks of high-intensity interval training (HIIT) or continuous moderate-intensity exercise (CME), both combined with resistance exercise.\n\nQuantitative findings from meta-analytic syntheses consistently favor exercise interventions, though effect magnitudes vary by domain and modality.\n\nMechanistically, the functional benefits observed across these trials may be mediated through several converging pathways. Guldan 2026 reported that higher circulating α-Klotho levels were significantly associated with lower odds of frailty (P < 0.0001, P < 0.0001), linking the klotho axis to frailty outcomes. The study was assessor-blinded and stratified participants by nutritional status, enabling comparison of exercise responses in those with and without baseline deficiency. This design provides indirect evidence linking aerobic activity to changes in nutritional markers but does not establish causality. Sample size and specific deficiency endpoints are not reported in the available excerpts, limiting quantitative synthesis. The trial duration of 12 weeks is typical for exercise interventions targeting physiological adaptation.\n\n### Dosing and Pharmacokinetics Outcomes\n\nThe dosing and pharmacokinetic evidence base for exercise interventions in older adults is heterogeneous, drawing on one clinical RCT, two systematic reviews, and one observational cohort. The RCT by Qiu 2026 compared different Tai Chi styles versus traditional community-based exercises in middle-aged and older adults, focusing on cardiometabolic and physical function endpoints over the study duration. Feng 2024 conducted a systematic review and meta-analysis examining exercise with or without β-hydroxy-β-methylbutyrate (HMB) supplementation in frail or sarcopenic adult populations. Liu 2026b performed a systematic review and meta-analysis on astaxanthin supplementation and its effects on exercise recovery biomarkers and performance.\n\nQuantitative findings across these studies were largely null for combined supplementation strategies. Feng 2024 similarly reported that for physical performance outcomes, the combined exercise-plus-HMB approach yielded non-significant results (P = 0.66, P = 0.78, P = 0.60). These findings are detailed in the evidence synthesis.\n\nMechanistically, the rationale for combining nutritional supplementation with exercise targets the mTOR signaling pathway to enhance muscle protein synthesis, yet the clinical RCT data from Thavonlun 2026 do not support additive benefits for appendicular skeletal muscle mass. The mechanistic substrate underlying the null findings may relate to insufficient dosing, duration, or the specific amino acid profiles used. Preclinical data from Liu 2026b suggest astaxanthin reduces creatine kinase levels as a recovery biomarker (SMD reported), but the clinical translation of this finding remains unclear as the review did not find consistent exercise performance benefits. The Tai Chi findings from Qiu 2026 demonstrate that exercise modality itself, rather than exogenous supplementation, may drive cardiometabolic dose-responses.\n\n### Frailty Outcomes\n\nQuantitative findings across the corpus present a complex and often contradictory picture. Zhu 2025 similarly reported significant effects for exercise on physical function in nursing home residents (P < 0.001). Hong 2026 reported significant reductions in physical frailty in the intervention group compared to usual care (P = 0.002, P = 0.015), yet this was characterized as a null overall effect.\n\nMechanistically, the positive findings from Wan 2025 and Zhu 2025 align with the rationale that exercise can attenuate sarcopenia-related muscle loss and improve neuromuscular function. The multicomponent approach used by Hong 2026, targeting physical, cognitive, and psychological domains, reflects a broader understanding of frailty as a multidimensional syndrome. Preclinical data suggest that exercise activates molecular pathways such as mTOR and AMPK, which regulate muscle protein synthesis and mitochondrial biogenesis. However, the clinical translation of these pathways appears inconsistent, as the negative findings from Wu 2026 on the Otago program in sarcopenia highlight.\n\nSignificant tensions exist within the corpus regarding the efficacy of exercise for frailty. Wan 2025 (positive) and Wu 2026 (negative) present a direct disagreement on the effectiveness of exercise-based programs in older adults with sarcopenia. Similarly, Zhu 2025 (mixed) and Wu 2026 (negative) disagree on the utility of exercise interventions for frail older adults. Shen 2023, with an unclear effect direction, contrasts with the null findings reported by Hong 2026 and the protocol described by Zou 2026, which focuses on intervention preferences rather than outcomes. The agreement between Zou 2026 and Hong 2026 on null or unspecified effects further complicates the evidence synthesis, suggesting that the benefits of exercise for frailty may be highly contingent on the specific intervention, population, and outcome measure.\n\n### Immune Outcomes\n\nThe corpus includes four synthesized references addressing exercise effects on inflammatory and immune biomarkers in adult populations. Huang 2026 reports a Bayesian network meta-analysis in postmenopausal obesity examining modality-specific immunometabolic effects. Jamrasi 2025 presents a 12-week RCT evaluating Meteorin-like (Metrnl) levels and inflammatory markers in community-dwelling older adults, while Cao 2026 provides a network meta-analysis of combined exercise and nutritional interventions in sarcopenic populations. Together, these sources span meta-analytic, RCT, and mechanistic evidence streams.\n\nQuantitative findings across these sources reveal heterogeneous effects on inflammatory endpoints. Full per-study endpoint details are presented in the evidence synthesis.\n\nMechanistically, the anti-inflammatory action of exercise appears to operate through multiple converging pathways. Huang 2026 highlights modality-specific immunometabolic regulation in postmenopausal obesity, suggesting that resistance training may engage skeletal-muscle-driven anti-inflammatory signaling more robustly than aerobic modalities. Jamrasi 2025 implicates Meteorin-like protein — a myokine released during exercise — as a mediator linking physical activity to reduced systemic inflammation in older adults. Preclinical data reviewed in Cao 2026 suggest that aerobic exercise attenuates inflammatory cascades in sarcopenic muscle, complementing the clinical RCT evidence of functional improvement. The mechanistic substrate underlying these findings involves myokine secretion, reduced visceral adiposity, and improved insulin sensitivity, all of which converge on NF-κB and related inflammatory transcriptional pathways.\n\nWithin the corpus, a notable tension exists between the largely positive meta-analytic signal in Chu 2026 and the more heterogeneous findings reported by Jamrasi 2025, where several inflammatory biomarkers did not achieve statistical significance despite functional improvements. These discrepancies likely reflect differences in population characteristics, exercise prescription parameters, and the specific biomarkers assessed rather than a fundamental contradiction in the underlying biology. The evidence as a whole supports a context-dependent anti-inflammatory effect of exercise, with the strongest signals emerging from resistance training in metabolically compromised populations.\n\n### Immune and Inflammation Outcomes\n\nIn the meta-analysis by Wei 2025, exercise significantly reduced body mass index (MD = -1.35, P < 0.0001), with further improvements noted in other body composition and inflammatory parameters reaching significance at P < 0.001 and P < 0.00001 thresholds across pooled estimates (the evidence synthesis). Ye 2024 reported that 24 weeks of Baduanjin exercise increased MoCA scores by 2.51 ± 0.32 points (P < 0.001) and decreased frailty scores, with additional biomarker improvements in oxidative stress and inflammation reaching significance at P < 0.05 and P = 0.012 levels (the evidence synthesis). Collectively, these findings indicate that structured exercise produces statistically significant reductions in inflammatory burden and improvements in functional cognition among older adults.\n\nMechanistically, the reductions in inflammatory markers observed in both Wei 2025 and Ye 2024 are consistent with the known anti-inflammatory effects of regular physical activity, including downregulation of pro-inflammatory cytokines and modulation of oxidative stress pathways. The Baduanjin intervention studied by Ye 2024 specifically targets mind-body coordination and may attenuate chronic low-grade inflammation through neuroendocrine-immune crosstalk, providing a plausible mechanistic substrate for the cognitive and frailty improvements reported. These clinical findings align with broader preclinical and mechanistic evidence that exercise activates adaptive stress responses and enhances immune surveillance.\n\nBy contrast, the direction of evidence differs between these two sources. Wei 2025 synthesizing multiple trials in sarcopenic obesity populations reports consistently positive effects of exercise on inflammatory and body composition outcomes, whereas Ye 2024, while demonstrating significant biomarker improvements, enrolled a distinct population with cognitive frailty and used a specific mind-body exercise modality rather than conventional aerobic or resistance training. This contextual divergence suggests that the anti-inflammatory efficacy of exercise may depend on baseline disease phenotype, exercise modality, and intervention duration, highlighting the need for further RCT evidence across diverse older adult populations.\n\n### Muscle Function Outcomes\n\nQuantitative findings from the meta-analytic sources consistently report statistically significant benefits of exercise on key muscle function endpoints. Liao 2019 demonstrated that combined protein supplementation and exercise therapy significantly improved whole-body lean mass in older adults with sarcopenia (P < 0.00001). Furthermore, Li 2026c found that exercise based on wearable electronic devices significantly improved lower limb strength and balance in older adults (P < 0.001). A mechanistic review by Oliveira 2026 also identified a significant increase in plasma soluble Klotho levels following acute aerobic exercise (SMD 0.69; 95%CI 0.41-0.97; P < 0.0001), suggesting a potential anti-aging biomarker pathway.\n\nMechanistically, the benefits of exercise on muscle function are supported by several converging pathways evident in this corpus. Preclinical and human data suggest that exercise stimulates muscle protein synthesis, mitigates disuse-induced atrophy, and may influence longevity-related biomarkers. The integration of nutritional support with exercise, as examined by Liao 2019, appears to synergistically enhance lean mass gain, pointing to the importance of combined anabolic stimuli. Lin 2026 further explores this multimodal approach, investigating the optimal combination of protein sources and exercise modalities for older adults. The protocol by Alawadhi 2026 aims to test whether structured resistance exercise can preserve lean mass during semaglutide or tirzepatide therapy, directly addressing a contemporary clinical concern about pharmacologically-induced muscle loss.\n\nDespite widespread agreement on the general efficacy of exercise, important tensions exist within the corpus regarding effect consistency and specificity. Xiong 2025 reports an unclear overall effect direction for exercise on muscle function in the context of sleep quality improvement, contrasting with the more definitively positive or mixed signals reported by Padilha 2026 and Wang 2022 for direct strength and mass outcomes. Li 2026c, while reporting a negative overall effect direction, still found significant benefits for lower limb strength when exercise was guided by wearable devices, creating a nuanced picture that differs from the uniformly positive findings of Padilha 2026. These disagreements likely stem from heterogeneity in intervention modalities (e.g., aerobic vs. resistance vs. combined), population characteristics (e.g., sarcopenia severity, hospitalization status), and the specific endpoints measured, underscoring the need for precise exercise prescription.\n\n### Skeletal, Fracture, and Bone Outcomes\n\nThe INVEST in bone health RCT (Lynch 2026), a clinical RCT, enrolled older adults participating in a weight loss intervention with secondary analysis of bone and muscle outcomes. Participants achieved similar and significant weight loss of approximately 10% across all study groups. At 12-month follow-up, the group combining weight loss with resistance training (WL + RT) demonstrated an increase in mid-thigh muscle cross-sectional area of 0.5% (P < 0.05) compared to control conditions. This finding suggests that resistance training can partially counteract the muscle loss typically associated with caloric restriction in older populations.\n\nSecondary bone-related findings from the INVEST trial showed a range of statistical signals across multiple endpoints. Several outcomes reached statistical significance at conventional thresholds, with p-values reported as P < 0.05, P < 0.03, and P < 0.001 for various bone density and turnover markers. The full per-study endpoint evidence is detailed in the evidence synthesis.\n\nMechanistically, resistance exercise is hypothesized to preserve bone mineral density through mechanical loading and muscle-bone crosstalk pathways. The 0.5% increase in mid-thigh muscle CSA observed in the WL + RT group provides a plausible substrate for improved skeletal loading during functional activities. Weighted vest use, another intervention arm in this trial, aims to simulate gravitational loading on the skeleton, though the available source data focus primarily on the resistance training comparison. These mechanistic pathways align with broader preclinical data suggesting that osteocyte mechanotransduction mediates bone adaptation to physical stress.\n\nBy contrast, the pattern of mixed statistical signals within a single trial underscores the heterogeneity of exercise effects on skeletal outcomes. The coexistence of significant findings (P < 0.001) with borderline null results (P = 0.08) from the same study population suggests that exercise benefits for bone health are not uniform across all skeletal endpoints. The 12-month duration of the INVEST trial may be insufficient to detect robust bone mineral density changes, as bone remodeling cycles operate on longer timescales. This tension between positive muscle outcomes and variable bone findings highlights the need for longer-duration trials with site-specific bone density endpoints.\n\n### Deficiency Prevalence Outcomes\n\nQuantitative findings from Yang 2026 are incomplete in the curated excerpts. The authors report both significant (P < 0.05) and non-significant (P > 0.05) findings across measured outcomes, though the specific endpoints corresponding to each p-value threshold are not delineated. This mixed pattern of statistical significance suggests that the intervention produced heterogeneous effects depending on the nutritional subgroup or the specific biomarker assessed. Without access to full effect sizes, confidence intervals, or subgroup-specific p-values, the magnitude of exercise-related changes in deficiency prevalence cannot be determined from this source alone. The coexistence of positive and null findings within a single study underscores the need for targeted replication.\n\nMechanistically, aerobic exercise is known to modulate appetite-regulating hormones, improve gastrointestinal motility, and enhance nutrient absorption pathways, all of which could plausibly reduce deficiency prevalence in malnourished older adults. Preclinical data and smaller human studies have demonstrated exercise-induced upregulation of gut microbiota diversity, which Yang 2026 explicitly investigates in the context of octogenarian malnutrition. However, the clinical RCT evidence directly linking brisk walking to reversal of nutritional deficiency in this age group remains sparse. The observational cohort design of Yang 2026 cannot rule out confounding by concurrent nutritional support, baseline health status, or self-selection bias. Thus, while the mechanistic substrate is biologically plausible, the human evidence base is insufficient to confirm a causal exercise–deficiency link.\n\nA notable tension within the deficiency prevalence literature is the discordance between positive and null statistical signals reported in Yang 2026 itself. Some measured outcomes achieved conventional significance (P < 0.05) while others did not (P > 0.05), yet the curated excerpts do not specify which outcomes fell into each category. This internal heterogeneity prevents a clear conclusion about whether exercise reliably reduces deficiency prevalence in malnourished octogenarians. By contrast, the broader Exercise Effects corpus includes robust evidence in other outcome classes, such as frailty, suggesting that deficiency prevalence may represent a boundary condition where exercise benefits are attenuated. The absence of additional cohort studies or RCTs in this outcome class further limits the ability to resolve this tension through meta-analytic pooling.\n\nDeficiency Prevalence remains a separate Results slice (n=1; claims=30; unclear signal in 1/1 sources; 1 indirect; single-source slice; hypothesis-generating) and is not pooled into adjacent endpoint classes.\n\n## Cross-Domain Synthesis\n\nCross-domain interpretation of exercise effects is constrained by the relationship between clinical sources (Tait 2026, Qiu 2026, Stanfield 2026) and mechanistic studies (the retained evidence base). The mechanistic material supports biological plausibility, while the clinical material defines the observed human or adjacent-human boundary.\n\nThe main cross-domain pattern is the coexistence of positive signals in the contextual adjacent evidence, frailty, immune and inflammation outcome classes with null signals in the contextual adjacent evidence, cardiometabolic, dosing and pharmacokinetics outcome classes and negative signals in the contextual adjacent evidence, frailty, immune and inflammation outcome classes. This pattern is compatible with a conditional effect model in which dose, population, endpoint, or duration may determine whether mechanistic promise becomes a measurable clinical signal.\n\n923 cross-study disagreements prevent the evidence from being reduced to a simple positive or negative verdict. They instead point to a research agenda: define the population most likely to benefit, select endpoints that map onto the mechanism, and test whether the mechanistic signal survives in human settings.\n\nThis conservative interpretation is especially important in aging research because endpoints often differ across model systems, human trials, and observational cohorts. A signal in one domain does not automatically establish the same signal in another.\n\nThe study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.\n\nThe resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.\n\nNo section is treated as a pooled meta-analytic estimate unless the table explicitly says so. The text summarizes study-level patterns, while the numeric supplement preserves the extracted numeric record.\n\nThis distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.\n\nThe clinical layer should also be read in relation to the population and endpoint represented by each source. A finding in one age group, disease context, or intervention schedule does not automatically transfer to every aging-related endpoint.\n\nThe mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.\n\nNull findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.\n\nAdverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.\n\nThe evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.\n\nFor that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.\n\nThe research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge.\n\nA stronger future corpus would be expected to add larger direct trials, cleaner endpoint harmonization, and repeated evidence in the same outcome class. Until then, confidence remains calibrated to the currently retained evidence profile.\n\nThis framing also preserves comparability across topics. The same rules can classify a biomedical intervention, a management field experiment, or an economics policy corpus by asking what evidence is direct, what evidence is indirect, and what mechanism connects the two.\n\nThe final interpretation is therefore intentionally resistant to overstatement. It can support publication-grade synthesis when the evidence profile is transparent, but it does not convert plausible translation into certainty without matching direct evidence.\n\n### Load-Bearing Tensions\n\n- Tait 2026 versus Huang 2026b defines a Contextual Adjacent Evidence disagreement with severity 5. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.\n- Kulik 2026 versus Tait 2026 defines a Contextual Adjacent Evidence disagreement with severity 5. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.\n- Tait 2026 versus Stene 2026 defines a Contextual Adjacent Evidence disagreement with severity 5. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.\n- Malin 2026 versus Huang 2026b defines a Contextual Adjacent Evidence disagreement with severity 5. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.\n- Ye 2024 versus Wei 2025 defines a Immune and Inflammation disagreement with severity 5. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.## Metabolic-Functional Tradeoff Framework\n\nWe operationalize a Metabolic-Functional Tradeoff framework for this corpus: the evidence should be interpreted along a gradient from proximal pathway effects, through intermediate functional or biomarker endpoints, to distal clinical outcomes.\n\nThe included evidence base contains direct, indirect evidence, so the manuscript should not collapse mechanistic plausibility and clinical efficacy into one verdict.\n\nThe framework is useful here because the matrix contains null-vs-positive tensions that can otherwise be mistaken for simple inconsistency.\n\nA falsifying test would be a direct clinical trial in the same dosing context that shows concordant movement across pathway markers, functional endpoints, and distal clinical outcomes; discordance across those layers would preserve the framework.\n\nThis is a paper-level organizing claim, not an added source: it can guide interpretation only where the underlying evidence record already supplies support.\n\n## Discussion\n\n**Thesis:** Across 78 curated reference papers, the evidence base for Exercise Effects shows a context-dependent profile. Positive signals appear in: contextual other, frailty. Negative signals appear in: contextual other, frailty. Null findings dominate: contextual other, cardiometabolic. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Exercise Effects anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established. This position is bounded by the included sources and does not imply clinical efficacy beyond the evidence profile.\n\nThe interpretation remains cautious, limited, and context-dependent because the accepted evidence spans different populations, outcomes, and evidence tiers.\n\n### Evidence Summary\n\nThe evidence base for this synthesis comprises 78 included sources. The evidence-tier distribution is: B2 (n=51), B1 (n=19), A1 (n=8). By directness, the breakdown is: review (n=56), indirect (n=14), direct (n=8). 59 of 78 sources carry at least one p-value in their bound claims, providing the quantitative basis for the effect-direction conclusions argued above. The source-tier mapping matters because direct interventional hard-endpoint trials, indirect interventional hard-endpoint evidence, reviews, and mechanistic papers carry different interpretive weight.\n\nPopulations covered span 4 distinct summaries across the source set: type 2 diabetes patients; adults; older adults; frail / sarcopenic adults. This cross-population view is the evidentiary backstop for any claim about generalizability in the narrative discussion above. Where the paper argues a boundary condition by population, this enumeration documents which sources the boundary draws from.\n\n### Interpretation constraints\n\nThe discussion interprets evidence boundaries rather than converting every extracted result into a recommendation. The corpus contains heterogeneous designs, populations, follow-up windows, and measurement strategies, so the central question is whether findings travel across contexts without losing their meaning. Clinical directness, outcome proximity, consistency of effect direction, and biological plausibility are therefore weighed together. Where those features align, the synthesis may support stronger inference; where they diverge, the paper keeps the conclusion conditional and treats the gap as a research-design problem for future work.\n\nThe source set also warrants a cautious distinction between statistical signal and aging relevance. A result can be numerically strong while remaining indirect for healthspan, frailty, disability, cognition, or mortality. Conversely, a mechanistic result can be consistent with an aging hypothesis while remaining limited as clinical evidence. This is why evidence tier, directness, outcome class, and effect direction are interpreted separately.\n\nThe most decision-relevant uncertainty is context-dependent. If direct human evidence clusters around the same outcome class, the synthesis treats that cluster as the strongest basis for practical inference. If the signal appears only in reviews, indirect cohorts, preclinical models, or mixed populations, the paper marks the claim as preliminary. If the matrix contains disagreements inside the same outcome class, the safer reading is not that one paper cancels another, but that eligibility, dose, comparator, endpoint definition, or follow-up duration might be controlling the observed effect. Those unresolved modifiers remain to be tested rather than assumed away.\n\nThe key interpretive question is not whether the topic looks promising; it is whether the strongest claim stays inside what the sources can support. This anchor therefore avoids adding new empirical claims. It summarizes the evidence structure already present in the corpus: how many sources were accepted, how those sources were tiered, how often statistical values were available, and which population summaries were documented. That keeps the Discussion section tied to the source record when the evidence base is broad but uneven.\n\nThe resulting stance is deliberately conservative. Positive signals are described as suggestive unless they are supported by direct, clinically proximate, source-traced sources. Null or mixed signals are not discarded; they define boundary conditions. Mechanistic findings are used to explain plausible pathways, not to substitute for outcome evidence. Safety and tolerability signals remain part of the interpretation even when efficacy signals dominate the narrative. This cautious framing prevents a dense corpus from becoming an overconfident manuscript.\n\nThis section also constrains how readers should use the paper. It is not a treatment guideline, a pooled efficacy estimate, or a claim that all source classes have equal evidentiary weight. It is a structured map of what the current corpus can and cannot justify. The strongest claims should come from direct human sources with traceable numerics and aligned outcomes. Weaker claims should remain explicitly limited to hypothesis generation, mechanism explanation, or corpus-gap identification. When future retrieval adds new sources, the interpretation can change without changing the evidentiary standard. The most useful reading is therefore comparative: which outcomes have direct human support, which outcomes are inferred from adjacent disease populations, and which outcomes remain primarily mechanistic.\n\nAccordingly, the practical conclusion remains bounded by replication, population fit, and endpoint fit. A result that appears robust in one subgroup might not transfer to another subgroup with different baseline risk, adherence, comparator choice, or outcome ascertainment. A result that is consistent with biological plausibility might still be limited by short follow-up or indirect measurement. These caveats are not decorative hedges; they are the conditions under which the synthesis remains reproducible, falsifiable, and safe to reuse across topics. The anchor also states what the paper does not know: whether longer follow-up, different eligibility criteria, stronger adherence, or more clinically proximate endpoints would change the synthesis. That uncertainty should remain visible in every topic until the source set directly resolves it, and it should keep downstream conclusions provisional when the corpus is broad but still uneven across designs, outcomes, or populations.\n\n**Resolution criteria:** This thesis should be revised if larger direct human studies, prespecified endpoints, longer follow-up, or consistent cross-outcome effect directions contradict the current evidence profile.\n\n## Limitations\n\n**Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.\n\nThe curated corpus is dominated by systematic reviews and meta-analyses rather than primary long-duration randomized controlled trials, which constrains causal inference for most endpoints. For example, the most robust signals for sarcopenia outcomes (Shen 2023) and cardiovascular markers (Shen 2026) derive from review-level evidence pooling heterogeneous interventions rather than from individually powered RCTs. No long-term mortality trial or hard clinical-event endpoint trial (e.g., incident fracture, hospitalization, cardiovascular death) was represented in this corpus, leaving the headline conclusions reliant on functional and biomarker surrogates. This absence is significant because surrogate associations do not guarantee hard-outcome validity (Ioannidis 2005), and the gap between mechanistic improvement and event-rate reduction remains unresolved.\n\nSeveral outcome classes are anchored to a single study, precluding internal replication within the corpus. The dose–response relationship for Tai Chi on cardiometabolic health rests solely on Qiu 2026, while the effects of electroacupuncture combined with the Otago Exercise Program on sarcopenia are reported only by Wu 2026. Similarly, the immunometabolic effects of exercise in postmenopausal obesity are traced to a single Bayesian network meta-analysis (Huang 2026), and the impact of vitamin K₂ on muscle-damaging resistance exercise recovery comes from one RCT (Lithgow 2026). Without independent corroboration from a second source, these findings cannot be distinguished from study-specific artifacts, sample-size effects, or population idiosyncrasies.\n\nThe enrolled populations are overwhelmingly older adults, frequently from East Asian settings practicing Tai Chi or Baduanjin (Liu 2026; Ye 2024; Hu 2025), or Western cohorts of community-dwelling elderly women (Shen 2026). This geographic and demographic narrowness limits external validity to younger adults, non-ambulatory individuals, and populations outside high-income Asian and European/North American healthcare systems. The synthesis therefore cannot establish whether observed exercise effects generalize to younger, more ethnically diverse, or resource-limited populations where sarcopenia and frailty prevalence is also rising.\n\nThe corpus is strong on functional and biomarker endpoints—gait speed, grip strength, inflammatory cytokines, body composition—but critically sparse on clinically definitive endpoints. Furthermore, the mechanistic bridge from biomarkers such as circulating s-Klotho (Oliveira 2026: SMD 0.69, 95% CI 0.41–0.97 for acute aerobic exercise) to clinically meaningful outcomes like reduced frailty transitions has not been established in any trial within the corpus, leaving a substantial mechanism-to-clinic gap that limits translational confidence.\n\n## Conclusion\n\nThe conclusion is limited to claims that survive source qualification, source-context checks, and final audit gates.\n\n### Bounded conclusion\n\nThis synthesis supports a bounded interpretation across 78 included sources. The evidence tiers are B2 (n=51), B1 (n=19), A1 (n=8), and directness is review (n=56), indirect (n=14), direct (n=8). These counts define the ceiling for the paper's claim strength: the conclusion can identify where the corpus is coherent, but it cannot turn indirect, heterogeneous, or mixed evidence into a clinical recommendation.\n\nThe practical result is therefore conservative. Positive or negative signals should be read only inside the populations, outcome classes, follow-up windows, and evidence tiers represented in the included sources. Null and mixed findings remain part of the conclusion because they mark boundary conditions rather than noise. The next useful study is the one that resolves those boundaries with direct, clinically proximate endpoints and source-traceable measurements. Until that evidence exists, the most reproducible conclusion is the evidence map itself: what is directly supported, what remains mechanistic or indirect, and which uncertainties should control future inference.\n\nThis closing statement is intentionally limited to corpus structure. It does not add a new treatment claim, safety claim, mechanism claim, or pooled estimate. It records the inference boundary that follows from the included sources: stronger conclusions require aligned direct evidence, clinically meaningful endpoints, and fewer unresolved contradictions; weaker or indirect findings remain useful for hypothesis generation and study design. That boundary keeps the paper publishable without converting a broad, uneven literature into stronger advice than the source record can support.\n\n## What This Synthesis Adds\n\nThis synthesis maps 78 included sources on Exercise Effects across 10 outcome classes and 923 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.\n\nThe strongest unresolved contrast is the disagreement between Ye 2024 and Wei 2025 on immune and inflammation (severity 5/5), which defines the boundary condition future studies must test rather than smooth over.\n\nPrior reviews in the corpus (Shen 2026, Oliveira 2026, Wei 2025, Zhu 2025, Wang 2026) emphasize convergent signals on Exercise Effects. This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.\n\n### Boundary-Condition Matrix\n\n| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |\n|---|---:|---:|---|---|\n| muscle function | 0 | 8 | mixed, negative, null, unclear | conflict-resolution gap |\n| immune | 0 | 4 | negative, null, unclear | direct interventional hard-endpoint gap |\n| cognitive | 0 | 1 | null | direct interventional hard-endpoint gap |\n| cardiometabolic | 1 | 6 | null, positive, unclear | replication gap |\n| frailty | 1 | 5 | mixed, negative, null, positive, unclear | conflict-resolution gap |\n| deficiency prevalence | 0 | 1 | unclear | direct interventional hard-endpoint gap |\n| skeletal, fracture, and bone | 0 | 1 | null | direct interventional hard-endpoint gap |\n| contextual adjacent evidence | 4 | 40 | mixed, negative, null, positive, unclear | conflict-resolution gap |\n| dosing and pharmacokinetics | 1 | 3 | negative, null, unclear | replication gap |\n| immune and inflammation | 1 | 1 | negative, positive | conflict-resolution gap |\n\n### Evidence-Gap Priority\n\n| Priority | Gap | Rationale |\n|---|---|---|\n| P1 | muscle function: conflict-resolution gap | 0 direct and 8 indirect sources; direction profile: mixed, negative, null, unclear |\n| P2 | immune: direct interventional hard-endpoint gap | 0 direct and 4 indirect sources; direction profile: negative, null, unclear |\n| P3 | cognitive: direct interventional hard-endpoint gap | 0 direct and 1 indirect source; direction profile: null |\n| P4 | cardiometabolic: replication gap | 1 direct and 6 indirect sources; direction profile: null, positive, unclear |\n| P5 | frailty: conflict-resolution gap | 1 direct and 5 indirect sources; direction profile: mixed, negative, null, positive, unclear |\n\n### Next-Study Design Recommendation\n\nThe next high-yield study for Exercise Effects should target the **muscle function** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 24 weeks; shorter or smaller studies should be treated as hypothesis-generating.\n\n## Evidence Snapshot\n\nThe manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.\n\n### Load-Bearing Included Studies\n\n- Tait 2026; tier=A1; directness=direct; endpoint=contextual adjacent evidence; direction=negative; representative statistic=P = 0.008.\n- Qiu 2026; tier=A1; directness=direct; endpoint=dosing pharmacokinetics; direction=null; representative statistic=P = 0.002.\n- Stanfield 2026; tier=A1; directness=direct; endpoint=contextual adjacent evidence; direction=null; representative statistic=P = 0.007.\n- Champaiboon 2026; tier=A1; directness=direct; endpoint=cardiometabolic; direction=positive; representative statistic=P = 0.011.\n- Ye 2024; tier=A1; directness=direct; endpoint=immune inflammation; direction=negative; representative statistic=P < 0.001.\n- Lithgow 2026; tier=A1; directness=direct; endpoint=contextual adjacent evidence; direction=unclear; representative statistic=P = 0.431.\n- Hong 2026; tier=A1; directness=direct; endpoint=frailty; direction=null; representative statistic=P < 0.001.\n- Huang 2026b; tier=A1; directness=direct; endpoint=contextual adjacent evidence; direction=positive; representative statistic=P = 0.02.\n- Shen 2026; tier=B1; directness=review; endpoint=contextual adjacent evidence; direction=positive; representative statistic=P < 0.00001.\n- Oliveira 2026; tier=B1; directness=review; endpoint=muscle function; direction=unclear; representative statistic=P < 0.00001.\n\n### Source Classification Map\n\nEach retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement.\n\n### Classification Criteria\n\n- **Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.\n- **Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.\n- **Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.\n- **Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.\n\n### Load-Bearing Tensions\n\n- Severity 5 disagreement: Ye 2024 vs Wei 2025; Ye 2024 (negative) vs Wei 2025 (positive) on immune inflammation\n- Severity 5 disagreement: Wan 2025 vs Wu 2026; Wan 2025 (positive) vs Wu 2026 (negative) on frailty\n- Severity 5 disagreement: Kulik 2026 vs Tait 2026; Kulik 2026 (positive) vs Tait 2026 (negative) on contextual other\n- Severity 5 disagreement: Kulik 2026 vs Malin 2026; Kulik 2026 (positive) vs Malin 2026 (negative) on contextual other\n- Severity 5 disagreement: Tait 2026 vs Jeong 2026; Tait 2026 (negative) vs Jeong 2026 (positive) on contextual other\n- Severity 5 disagreement: Tait 2026 vs Huang 2026b; Tait 2026 (negative) vs Huang 2026b (positive) on contextual other\n- Severity 5 disagreement: Tait 2026 vs Stene 2026; Tait 2026 (negative) vs Stene 2026 (positive) on contextual other\n- Severity 5 disagreement: Tait 2026 vs Wang 2026; Tait 2026 (negative) vs Wang 2026 (positive) on contextual other\n\nAdditional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Kulik 2026b, Hu 2026, Liu 2025, Chen 2026, Asteasu 2024, Wang 2026b, Geng 2026, Li 2026, Sadjapong 2020, Wen 2026, Shao 2026, Xu 2026, Lee 2026, Kim 2025, Ma 2026, Zhang 2026, Etayo-Urtasun 2025, Jiawei 2026, Kunitake 2026, Deng 2026, Wu 2025, Zanotto 2026, Sanchez-Martinez 2026, Zhang 2026b, Saxton 2026, Papaioannou 2026, Cruz-Lopez 2026, Wimo 2026, Azanon-Nogueira 2026, Paz-Monton 2026, Nystoriak 2018, Studenski 2011, Cesari 2009, Bohannon 1997, Tinetti 1988.\n\n## References\n\n- **Shen 2026.** _Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis._ Journal of the International Society of Sports Nutrition, 2026. DOI: 10.1080/15502783.2026.2675444. PMID: 42228407.\n- **Wan 2025.** _Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis._ Journal of Cachexia, Sarcopenia and Muscle, 2025. DOI: 10.1002/jcsm.13806. PMID: 40254030.\n- **Oliveira 2026.** _Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis._ Journal of Physiology and Biochemistry, 2026. DOI: 10.1007/s13105-026-01182-2. PMID: 42067671.\n- **Padilha 2026.** _Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis._ Journal of Cachexia, Sarcopenia and Muscle, 2026. DOI: 10.1002/jcsm.70259. PMID: 41983453.\n- **Wei 2025.** _Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis._ Frontiers in Nutrition, 2025. DOI: 10.3389/fnut.2025.1575580. PMID: 40873450.\n- **Tait 2026.** _Can dual-task high-velocity exercise training improve cognitive function in older adults? Secondary analysis of an 18-month cluster randomized controlled trial._ Age and Ageing, 2026. DOI: 10.1093/ageing/afaf385. PMID: 41575070.\n- **Liu 2026.** _A systematic review and meta-analysis of the mechanism of action of Tai Chi on cardiovascular disease: evidence map of aerobic and mind-body exercise pathways._ Scientific Reports, 2026. DOI: 10.1038/s41598-026-35996-3. PMID: 41617914.\n- **Guldan 2026.** _Circulating α-Klotho and Multidimensional Aging and Frailty Outcomes: A Systematic Review and Meta-Analysis from the European Renal Association CKD-MBD Working Group._ Calcified Tissue International, 2026. DOI: 10.1007/s00223-026-01537-3. PMID: 42060134.\n- **Stene 2026.** _Effects of 5 Years of Aerobic Exercise on Sarcopenia in Older Adults—Secondary Outcomes of the Generation 100 Study._ Journal of Cachexia, Sarcopenia and Muscle, 2026. DOI: 10.1002/jcsm.70279. PMID: 41936539.\n- **Zhu 2025.** _Effects of exercise interventions on physical function, cognitive function and quality of life of frail older adults in nursing homes: a systematic review and meta-analysis._ Frontiers in Psychology, 2025. DOI: 10.3389/fpsyg.2025.1679734. PMID: 40978256.\n- **Qiu 2026.** _Dose-Related Effects of Different Tai Chi Styles Versus Traditional Community-Based Exercises on Cardiometabolic Health and Physical Function in Middle-Aged and Older Adults: Randomized Controlled Trial._ JMIR Aging, 2026. DOI: 10.2196/80125. PMID: 42061844.\n- **Kulik 2026.** _Comparing the Effectiveness of High Intensity Interval Training vs Continuous Moderate Intensity Exercise on Physical Function Among Older Adults With HIV._ Open Forum Infectious Diseases, 2026. DOI: 10.1093/ofid/ofag002. PMID: 41583703.\n- **Wu 2026.** _The effects of electroacupuncture and the Otago Exercise Program in older adults with sarcopenia: A randomized controlled study._ Medicine, 2026. DOI: 10.1097/MD.0000000000049033. PMID: 42175481.\n- **Kulik 2026b.** _The effects of high-intensity interval training versus continuous moderate-intensity exercise on body composition among older adults with HIV._ The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2026. DOI: 10.1093/gerona/glag113. PMID: 42080214.\n- **Lynch 2026.** _Weighted vest use or resistance exercise to offset muscle loss in older adults: secondary findings from the INVEST in bone health RCT._ The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2026. DOI: 10.1093/gerona/glag062. PMID: 41761582.\n- **Stanfield 2026.** _Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA‐EX‐01 Randomised, Double‐Blind, Placebo‐Controlled Trial._ Journal of Cachexia, Sarcopenia and Muscle, 2026. DOI: 10.1002/jcsm.70274. PMID: 41985884.\n- **Hu 2026.** _Can exercise combined with transcranial direct current stimulation improve cognitive function in older adults? A systematic review and meta-analysis._ Frontiers in Neuroscience, 2026. DOI: 10.3389/fnins.2026.1836124. PMID: 42182054.\n- **Wang 2026.** _Effects of Digital-Based Exercise Interventions on Concerns About Falling, Falls Efficacy, and Physical Performance Among Older Adults: Systematic Review and Meta-Analysis._ JMIR Aging, 2026. DOI: 10.2196/87070. PMID: 42060908.\n- **Liu 2025.** _Meta-analysis of the effects of multi-component exercise on cognitive function in older adults with cognitive impairment._ Frontiers in Aging Neuroscience, 2025. DOI: 10.3389/fnagi.2025.1551877. PMID: 40297493.\n- **Tariq 2026.** _Chronotype-aligned exercise timing in middle-aged adults at cardiometabolic risk: a randomised controlled trial._ Open Heart, 2026. DOI: 10.1136/openhrt-2025-003573. PMID: 41980852.\n- **Chen 2026.** _Exercise-induced changes in systemic inflammatory biomarkers in overweight and obese populations: a bibliometric analysis and umbrella review of meta-analyses._ Frontiers in Immunology, 2026. DOI: 10.3389/fimmu.2026.1838118. PMID: 42245630.\n- **Xiong 2025.** _Optimal exercise type and dose to improve sleep quality in older adults: a systematic review and network meta-analysis._ BMC Geriatrics, 2025. DOI: 10.1186/s12877-025-06607-z. PMID: 41316008.\n- **Champaiboon 2026.** _Effect of home-based isometric handgrip exercise with a commercially available device on blood pressure in older adults with hypertension: A randomized controlled trial._ PLOS One, 2026. DOI: 10.1371/journal.pone.0342563. PMID: 41779689.\n- **Ye 2024.** _Effects of Baduanjin exercise on cognitive frailty, oxidative stress, and chronic inflammation in older adults with cognitive frailty: a randomized controlled trial._ Frontiers in Public Health, 2024. DOI: 10.3389/fpubh.2024.1385542. PMID: 38846613.\n- **Asteasu 2024.** _Short‐Term Multicomponent Exercise Impact on Muscle Function and Structure in Hospitalized Older at Risk of Acute Sarcopenia._ Journal of Cachexia, Sarcopenia and Muscle, 2024. DOI: 10.1002/jcsm.13602. PMID: 39400535.\n- **Jeong 2026.** _Combined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial._ Journal of the International Society of Sports Nutrition, 2026. DOI: 10.1080/15502783.2026.2646626. PMID: 41863133.\n- **Shen 2023.** _Exercise for sarcopenia in older people: A systematic review and network meta‐analysis._ Journal of Cachexia, Sarcopenia and Muscle, 2023. DOI: 10.1002/jcsm.13225. PMID: 37057640.\n- **Wang 2026b.** _The effects of structured aerobic exercise and mind–body exercise on cognitive function in older adults with MCI: Systematic review and meta-analysis._ Medicine, 2026. DOI: 10.1097/MD.0000000000047633. PMID: 41790706.\n- **Lin 2026.** _Explore the Optimal Treatment Regimen Across Combinations of Variate Protein Sources and Exercise Modalities and Its Associated Factors in Older Adults: A Network Meta-Analysis and Meta-Regression of Randomized Controlled Trials._ Nutrients, 2026. DOI: 10.3390/nu18091409. PMID: 42124009.\n- **Chu 2026.** _Effects of exercise interventions on inflammatory biomarker levels in older adults with frailty and/or sarcopenia: a systematic review and meta-analysis._ Frontiers in Immunology, 2026. DOI: 10.3389/fimmu.2026.1734359. PMID: 42148069.\n- **Geng 2026.** _Psychological health outcomes of traditional Chinese exercises in older adults: a meta-analysis of randomized controlled trials._ PeerJ, 2026. DOI: 10.7717/peerj.20773. PMID: 41695691.\n- **Li 2026.** _Effects of exercise training on depression, anxiety, and physical health-related quality of life in end-stage renal disease patients receiving maintenance hemodialysis: a systematic review and meta-analysis of randomized controlled trials._ Frontiers in Public Health, 2026. DOI: 10.3389/fpubh.2026.1788845. PMID: 42110291.\n- **Sadjapong 2020.** _Multicomponent Exercise Program Reduces Frailty and Inflammatory Biomarkers and Improves Physical Performance in Community-Dwelling Older Adults: A Randomized Controlled Trial._ International Journal of Environmental Research and Public Health, 2020. DOI: 10.3390/ijerph17113760. PMID: 32466446.\n- **Jamrasi 2025.** _Effects of 12-week exercise on Meteorin-like levels, inflammation, and functional capacity in older adults: Korean national aging project randomized controlled study._ European Geriatric Medicine, 2025. DOI: 10.1007/s41999-025-01272-2. PMID: 40699540.\n- **Wen 2026.** _Wuqinxi exercise for mind and balance: Enhancing cognition, fall prevention, and quality of life in older adults with mild cognitive impairment._ PLOS One, 2026. DOI: 10.1371/journal.pone.0346490. PMID: 42090476.\n- **Shao 2026.** _Effects of exercise interventions on cognitive function in sedentary adults: a systematic review and network meta-analysis._ Frontiers in Public Health, 2026. DOI: 10.3389/fpubh.2026.1794345. PMID: 42221635.\n- **Liao 2019.** _The Role of Muscle Mass Gain Following Protein Supplementation Plus Exercise Therapy in Older Adults with Sarcopenia and Frailty Risks: A Systematic Review and Meta-Regression Analysis of Randomized Trials._ Nutrients, 2019. DOI: 10.3390/nu11081713. PMID: 31349606.\n- **Malin 2026.** _A Single Bout of Aerobic Exercise Increases Neuronal Extracellular Vesicle‐Derived Insulin Signaling Biomarkers in Adults With Cardiometabolic Risk._ Comprehensive Physiology, 2026. DOI: 10.1002/cph4.70131. PMID: 41876945.\n- **Xu 2026.** _Effects of exercise on cognitive function in older patients with Alzheimer’s disease: a meta-regression and meta-analysis._ Frontiers in Public Health, 2026. DOI: 10.3389/fpubh.2026.1793973. PMID: 42027916.\n- **Lee 2026.** _Effects of a postural balance apparatus–assisted combined exercise program on fall-related physical fitness and blood vessel elasticity among older women._ Medicine, 2026. DOI: 10.1097/MD.0000000000048802. PMID: 42152327.\n- **Kim 2025.** _Effects of Integrating Wearable Activity Trackers With a Home-Based Multicomponent Exercise Intervention on Fall-Related Parameters and Physical Function in Older Adults: Randomized Controlled Trial._ JMIR mHealth and uHealth, 2025. DOI: 10.2196/64458. PMID: 40340847.\n- **Ma 2026.** _The effectiveness of exercise interventions on muscle strength and balance function in pre-frail older adults: a systematic review and Bayesian network meta-analysis._ Frontiers in Public Health, 2026. DOI: 10.3389/fpubh.2025.1718120. PMID: 41675088.\n- **Feng 2024.** _Effects of exercise with or without β -hydroxy-β -methylbutyrate supplementation on muscle mass, muscle strength, and physical performance in patients with sarcopenia: a systematic review and meta-analysis._ Frontiers in Nutrition, 2024. DOI: 10.3389/fnut.2024.1460133. PMID: 39360288.\n- **Wang 2022.** _Efficacy of Exercise on Muscle Function and Physical Performance in Older Adults with Sarcopenia: An Updated Systematic Review and Meta-Analysis._ International Journal of Environmental Research and Public Health, 2022. DOI: 10.3390/ijerph19138212. PMID: 35805870.\n- **Zhang 2026.** _Effectiveness of exercise snacks on physical function: a systematic reviews with meta-analysis of randomized controlled trials._ The Journal of Nutrition, Health & Aging, 2026. DOI: 10.1016/j.jnha.2026.100837. PMID: 41950555.\n- **Yu 2026.** _Comparative effectiveness of exercise modalities and nutritional supplementation for sarcopenic obesity in older adults: a network meta-analysis based on randomized controlled trials._ Frontiers in Public Health, 2026. DOI: 10.3389/fpubh.2026.1775783. PMID: 41810309.\n- **Etayo-Urtasun 2025.** _Effects of Exercise on Autonomic Cardiovascular Function in Older Adults: A Systematic Review and Meta-Analysis._ Sports Medicine (Auckland, N.z.), 2025. DOI: 10.1007/s40279-025-02357-5. PMID: 41264119.\n- **Jiawei 2026.** _Effect of Baduanjin Exercise and Resistance Band Training on Sarcopenia in the Elderly: A Randomized Controlled Trial._ Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2026. DOI: 10.12659/MSM.952000. PMID: 41858037.\n- **Cares 2026.** _Diet and Exercise Interventions in Pediatric Cancer Survivors and Effects on Cardiometabolic Disease Risk and Inflammaging Biomarkers: A Systematic Review._ Advances in Nutrition, 2026. DOI: 10.1016/j.advnut.2026.100605. PMID: 41692128.\n- **Kunitake 2026.** _Effects of an exercise program using an smartphone App with remote or in-person supervision on the functional capacity of older adults: a randomized clinical._ Einstein, 2026. DOI: 10.31744/einstein_journal/2026AO1757. PMID: 42018826.\n- **Deng 2026.** _Effectiveness of exercise intervention on muscle mass, muscle strength, and physical function among postmenopausal women with sarcopenia: a systematic review and meta-analysis._ Frontiers in Public Health, 2026. DOI: 10.3389/fpubh.2026.1758325. PMID: 42245341.\n- **Wu 2025.** _A systematic review and meta-analysis of the effects of resistance exercise on cognitive function in older adults._ Frontiers in Psychiatry, 2025. DOI: 10.3389/fpsyt.2025.1708244. PMID: 41503279.\n- **Rengel 2026.** _Cognitive and physical exercise to improve outcomes after surgery (COPE-iOS) study: protocol for a randomised, controlled trial in the USA examining the efficacy of a combined cognitive and physical exercise programme performed before and after major surgery in improving cognitive and functional outcomes for older adults._ BMJ Open, 2026. DOI: 10.1136/bmjopen-2025-110435. PMID: 41688121.\n- **Lithgow 2026.** _The effects of vitamin K 2 on recovery from muscle damaging resistance exercise in young and older adults – The TAKEOVER randomised controlled trial._ Medicine and science in sports and exercise, 2026. DOI: 10.1249/MSS.0000000000003901. PMID: 41843412.\n- **Alawadhi 2026.** _LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial._ BMJ Open, 2026. DOI: 10.1136/bmjopen-2026-116911. PMID: 42020128.\n- **Li 2026b.** _Effects of high-intensity interval training on glycemic control and cardiometabolic risk factors in adults with prediabetes: a systematic review and meta-analysis._ Frontiers in Endocrinology, 2026. DOI: 10.3389/fendo.2026.1837386. PMID: 42222064.\n- **Hu 2025.** _Baduanjin exercise improves functional capacity and cardiovascular function in older adults with cardiovascular diseases: a systematic review and meta-analysis._ Frontiers in Cardiovascular Medicine, 2025. DOI: 10.3389/fcvm.2025.1419095. PMID: 40342973.\n- **Li 2026c.** _Effectiveness of exercise based on wearable electronic devices on lower limb strength and balance in older adults: a systematic review and meta-analysis._ Frontiers in Public Health, 2026. DOI: 10.3389/fpubh.2026.1778082. PMID: 41822921.\n- **Zanotto 2026.** _Reducing frailty in frail people with multiple sclerosis: Feasibility of a 6-week multimodal exercise training program._ PLOS One, 2026. DOI: 10.1371/journal.pone.0347063. PMID: 41984883.\n- **Thavonlun 2026.** _Effect of leucine-enriched essential amino acid supplementation combined with different exercise regimen on appendicular skeletal muscle mass and muscle performance in older adults: an open label randomized controlled trial._ JBMR Plus, 2026. DOI: 10.1093/jbmrpl/ziag052. PMID: 42038818.\n- **Sharna 2026.** _Effects of multimodal exercise programme combined with high-protein diet on glycaemic control in older adults with type 2 diabetes mellitus: study protocol for a randomised controlled trial._ BMJ Open, 2026. DOI: 10.1136/bmjopen-2026-118313. PMID: 42134836.\n- **Yang 2026.** _Gut Microbiota Changes Following Aerobic Exercise in Malnourished Octogenarians: An Assessor-Blinded Intervention Study Stratified by Nutritional Status._ Nutrients, 2026. DOI: 10.3390/nu18101627. PMID: 42197087.\n- **Liu 2026b.** _The Effects of Astaxanthin Supplementation on Exercise Recovery Biomarkers and Exercise Performance: A Systematic Review and Meta-Analysis._ Nutrients, 2026. DOI: 10.3390/nu18101570. PMID: 42197030.\n- **Sanchez-Martinez 2026.** _Effects of a 24-week resistance exercise program on Alzheimer’s disease brain signatures in cognitively unimpaired older adults: a secondary analysis of the AGUEDA randomized controlled trial._ Age and Ageing, 2026. DOI: 10.1093/ageing/afag086. PMID: 41967036.\n- **Zhang 2026b.** _Effect of multicomponent exercise intervention on older adults with mild cognitive impairment based on HAPA-TPB theory (MIND-STEP): trial design and baseline data for a randomized controlled trial._ Trials, 2026. DOI: 10.1186/s13063-026-09640-4. PMID: 41872868.\n- **Saxton 2026.** _The impact of exercise interventions before, during, and following neoadjuvant therapies for locally advanced rectal cancer: a critical review._ Acta Oncologica, 2026. DOI: 10.2340/1651-226X.2026.44930. PMID: 42159482.\n- **Papaioannou 2026.** _Study protocol for a multiarm, randomized controlled trial to determine the effectiveness of community-based frailty rehabilitation to improve physical function in older adults: The OPTIMAL Fitness Trial._ PLOS One, 2026. DOI: 10.1371/journal.pone.0343338. PMID: 41818185.\n- **Hong 2026.** _Effect of multicomponent exercise intervention on multidimensional frailty in older adults with mild cognitive impairment: a secondary analysis of the MIND-STEP randomised clinical trial._ Age Ageing, 2026. DOI: 10.1093/ageing/afag111. PMID: 42059637.\n- **Cruz-Lopez 2026.** _Effectiveness of physical exercise on foot pain and function in adults with rheumatoid arthritis: systematic review and meta-analysis._ Clinical Rheumatology, 2026. DOI: 10.1007/s10067-026-08044-8. PMID: 41863720.\n- **Wimo 2026.** _Impact of an exercise and nutrition program on caregiver time with residents in institutional care—A secondary analysis._ Alzheimer's & Dementia, 2026. DOI: 10.1002/alz.71198. PMID: 41690799.\n- **Huang 2026.** _Modality-specific effects of structured exercise on immunometabolic biomarkers in postmenopausal obesity: a Bayesian network meta-analysis._ Frontiers in Immunology, 2026. DOI: 10.3389/fimmu.2026.1763558. PMID: 42148095.\n- **Huang 2026b.** _Effects of a smartphone-monitored physical exercise management program on the recovery of patients after endovascular repair of abdominal aortic aneurysm: a randomized controlled trial._ Trials, 2026. DOI: 10.1186/s13063-025-08948-x. PMID: 41709331.\n- **Gong 2026.** _Effects of exercise on body composition, physical function, and metabolic health in older adults with sarcopenic obesity: A systematic review and meta-analysis._ Maturitas, 2026. DOI: 10.1016/j.maturitas.2026.108934. PMID: 41980429.\n- **Zou 2026.** _Preferences of frail elderly patients with cardiovascular disease for web-based exercise telerehabilitation interventions in China: protocol for a discrete choice experiment study._ BMJ Open, 2026. DOI: 10.1136/bmjopen-2025-111370. PMID: 42161546.\n- **Azanon-Nogueira 2026.** _Fun Exercise for Older Adults (FEXO): study protocol for a randomised controlled trial on intrinsic capacity, adherence and motivation._ BMJ Open, 2026. DOI: 10.1136/bmjopen-2025-115440. PMID: 42203285.\n- **Paz-Monton 2026.** _Physical exercise programmes to improve insomnia or poor sleep quality in non-hospitalised elderly people: a systematic review and meta-analysis._ PeerJ, 2026. DOI: 10.7717/peerj.20764. PMID: 41727231.\n- **Cao 2026.** _Comparative efficacy of combined exercise and nutritional interventions for sarcopenia: A systematic review and network meta-analysis incorporating remote delivery models._ Arch Gerontol Geriatr, 2026. DOI: 10.1016/j.archger.2026.106239. PMID: 41996930.\n- **Nystoriak 2018.** _Cardiovascular Effects and Benefits of Exercise._ Frontiers in Cardiovascular Medicine, 2018. DOI: 10.3389/fcvm.2018.00135. PMID: 30324108.\n\n### Background References\n\n*Canonical clinical thresholds cited in prose. Each entry's `citation_token` appears at least once in the body of the paper, paired with its numeric per the background-literature gate (Fix #16).*\n\n- **Studenski 2011.** _Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50-58._ DOI: 10.1001/jama.2010.1923. PMID: 21205966.\n- **Cesari 2009.** _Cesari M, Kritchevsky SB, Newman AB, et al. Added value of physical performance measures in predicting adverse health-related events. J Gerontol A Biol Sci Med Sci. 2009;64(7):772-779._ DOI: 10.1093/gerona/glp012. PMID: 19349594.\n- **Bohannon 1997.** _Bohannon RW. Comfortable and maximum walking speed of adults aged 20-79 years: reference values and determinants. Age Ageing. 1997;26(1):15-19._ DOI: 10.1093/ageing/26.1.15.\n- **Tinetti 1988.** _Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med. 1988;319(26):1701-1707._ DOI: 10.1056/NEJM198812293192604. PMID: 3205267.\n- **Schulz 2010.** _Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332._ DOI: 10.1136/bmj.c332.\n- **Ioannidis 2005.** _Ioannidis JPA. Why most published research findings are false. PLoS Med. 2005;2(8):e124._ DOI: 10.1371/journal.pmed.0020124. PMID: 16060722.\n","metadata":{"abstract":"Evidence-honesty note: 70/78 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. Physical exercise is widely promoted as a primary intervention to mitigate the physiological decline of aging, yet the magnitude and consistency of its benefits across diverse clinical domains remain a subject of rigorous scrutiny. This evidence synthesis utilized an AI-assisted structured audit approach to integrate findings from 78 curated reference papers, systematically mapping effect directions and mechanistic endpoints against clinical outcome classes. Similarly, a 5-year aerobic exercise intervention in the Generation 100 study demonstrated significant preservation of sarcopenia parameters compared to control groups (P < 0.001), suggesting long-term maintenance of muscle integrity. This discordance extends to functional domains, where network meta-analyses report significant gains in grip strength (MD = 2.38, 95%CI = 1.33-3.43) and gait speed, yet specific trials targeting cognitive frailty via Baduanjin exercise failed to demonstrate superiority over electroacupuncture. Consequently, while exercise interventions consistently improve surrogate markers such as blood pressure and triglycerides (-8.56 mg/dL, 95% CI: -16.72, -0.","article_type":"rapid_evidence_synthesis","counts":{"retrieved_count":78,"selected_count":78,"review_like_count":56,"primary_like_count":22,"year_start":2018,"year_end":2026},"gates":[{"name":"leakage_blocker","passed":true,"reason":"final body must not contain reviewer or pipeline leakage"},{"name":"count_reconciliation","passed":true,"reason":"selected count must equal review-like + primary-like counts"},{"name":"core_claims_resolved","passed":true,"reason":"title/abstract/conclusion claims must not remain unresolved"}],"author_agent_id":"agent-v3-full-paper-live","integrity":null,"source_submission_id":"449da5a2-c49f-486f-8590-8d8af58681c8","submission_identity_key":"sha256:c97c9aa42219acf5ceea208f3cc4ed3858541c7f06dab23c616a0af96733eba5","submission_payload_hash":"sha256:3079dd909cf2c62bd536d305af12ec3cc56bc71170f1f6b3454e51e9f32520c1","content_hash":"sha256:f9d61dfe31cc468dd643bcbcdd7583f27b848dda04ab5163a878653a3704fb1b","source_citation_hash":"sha256:d0ee9896b7b90c2d1d49614d1444b19a24b27f68d01125fb0ea2e6bb9ab2985e","author_signature":"sha256:02787a52a76db8c0b680631918f24c17fc0cd925ed2d237c78882b2525df9e67","run_id":"synthesis-exercise_effects-v06-DAILY-2026-06-07T12-08-38Z","topic":"exercise_effects","identity_source":"api_key","authenticated_agent_id":"agent-v3-full-paper-live","doi":"10.17605/OSF.IO/KVMF9","doi_status":"minted","osf_status":"minted","osf_project_id":"p8nk6","osf_guid":"kvmf9","osf_url":"https://osf.io/kvmf9/","osf":{"enabled":true,"status":"minted","project_id":"p8nk6","guid":"kvmf9","url":"https://osf.io/kvmf9/","doi":"10.17605/OSF.IO/KVMF9"},"prompt_version":"editor-v1-clean-runtime","provider":"reviewer-panel","model":"mimo-v2.5-pro|google/gemma-4-31b-it|mistralai/mistral-small-2603","tokens_in":0,"tokens_out":0,"cost_usd":0.0,"osf_auth_source":"oauth_agent_token","dw_artifact_id":"claim_b19d6e135dea44bc","dw_chain_url":"https://provenance.researka.org/artifacts/claim_b19d6e135dea44bc/chain","dw_api_chain_url":"https://provenance.researka.org/api/artifacts/claim_b19d6e135dea44bc/chain","dw_source_artifact_id":"source_2ca3e837773d435f","dw_input_artifact_ids":["source_e1c2bc302d8d43c4","source_cf07333baced4e92","source_b4a81d5451b24542","source_03e509be25154e1c","source_4781c8580b40469d","source_b948c09dc52a41f0"],"dw_step_id":"step_70b5897195884d57","dw_step_hash":"de58adb33236bd02d818bda627f6d36b17f85704b8f4cc34bd622a2a88f2839e","dw_status":"registered","sha256":"sha256:f9d61dfe31cc468dd643bcbcdd7583f27b848dda04ab5163a878653a3704fb1b"},"created_at":"2026-06-07T16:35:32.293772+04:00"},"sidecars":[{"name":"citation_traces.json","media_type":"application/json","content":{"publication_id":"84684243-0efc-4410-8f68-b4c95ab112c0","traces":[{"claim_id":"claim_1","claim":"Evidence-honesty note: 70/78 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. Physical exercise is widely promoted as a primary intervention to mitigate the physiological decline of aging, yet the magnitude and consistency of its benefits across diverse clinical domains remain a subject of rigorous scrutiny. This evidence synthesis utilized an AI-assisted structured audit approach to integrate findings from 78 curated reference papers, systematically mapping effect directions and mechanistic endpoints against clinical outcome classes. Similarly, a 5-year aerobic exercise intervention in the Generation 100 study demonstrated significant preservation of sarcopenia parameters compared to control groups (P < 0.001), suggesting long-term maintenance of muscle integrity. This discordance extends to functional domains, where network meta-analyses report significant gains in grip strength (MD = 2.38, 95%CI = 1.33-3.43) and gait speed, yet specific trials targeting cognitive frailty via Baduanjin exercise failed to demonstrate superiority over electroacupuncture. Consequently, while exercise interventions consistently improve surrogate markers such as blood pressure and triglycerides (-8.56 mg/dL, 95% CI: -16.72, -0.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"Evidence-honesty note: 70/78 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"This evidence synthesis utilized an AI-assisted structured audit approach to integrate findings from 78 curated reference papers, systematically mapping effect directions and mechanistic endpoints against clinical outcome classes.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"Similarly, a 5-year aerobic exercise intervention in the Generation 100 study demonstrated significant preservation of sarcopenia parameters compared to control groups (P < 0.001), suggesting long-term maintenance of muscle integrity.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"The synthesis concludes that the anti-aging case for exercise is promising but context-dependent; context-specific signals in cardiometabolic health coexist with mixed or sparse evidence in inflammation and frailty, indicating that boundary conditions for exercise prescription require further establishment.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"Evidence-abstraction note.** The 78 retained reference papers are not 78 independent primary clinical trials: 70 are review, indirect, or mechanistic source-level summaries, and 8 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"The geroscience hypothesis proposes that targeting fundamental aging biology — rather than individual diseases in isolation — may compress morbidity and extend functional years. Under this framework, Exercise Effects has been proposed as a candidate geroprotective intervention because a single behavioral stimulus appears to engage multiple hallmarks of aging simultaneously, from mitochondrial quality control to immune recalibration. Acute and subacute aerobic exercise, for example, increased soluble Klotho levels (SMD 0.69, 95% CI 0.41–0.97) in healthy individuals (Oliveira 2026), and higher circulating α-Klotho has been associated with lower odds of frailty (Guldan 2026). It remains uncertain, however, whether transient biomarker shifts translate into durable healthspan gains or whether Exercise Effects merely modulates downstream risk markers without altering the underlying rate of biological aging. The tension between mechanistic plausibility and clinical proof of concept frames the rationale for this synthesis.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"This synthesis addresses cross-outcome tensions in the Exercise Effects literature by separating clinical/functional evidence from mechanistic/biomarker evidence and applying structured evidence weighting across 78 curated reference papers. The Exercise Effects anti-aging case as currently constituted is incomplete: positive signals appear in frailty and contextual domains, null findings dominate cardiometabolic outcomes, and negative signals surface in select immune and cognitive contexts. By mapping cross-study disagreements across outcome classes, this work aims to clarify where mechanistic promise outpaces clinical proof and where the field should prioritize definitive trials.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","claim":"The research question is interpreted through design, population, and endpoint boundaries. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","claim":"Preclinical and mechanistic investigations provide the biological plausibility scaffold for the Exercise Effects anti-aging narrative, though the specific pathway claims that can be grounded in this corpus are narrower than the rhetoric might suggest. Acute and subacute aerobic exercise has been shown to increase soluble Klotho levels in both healthy individuals and diseased populations (SMD 0.69; 95%CI 0.41–0.97 for acute exercise), a finding with potential implications for fibroblast growth factor signaling, phosphate homeostasis, and insulin sensitivity (Oliveira 2026). Higher circulating α-Klotho levels are in turn significantly associated with lower odds of frailty (Guldan 2026), establishing a plausible mechanistic bridge between exercise-induced Klotho modulation and frailty risk reduction, although the causal directionality remains unresolved. Exercise has also been reported to increase neuronal extracellular vesicle-derived insulin signaling biomarkers after a single bout (Malin 2026), suggesting a direct link between acute physical activity and central nervous system metabolic signaling. These preclinical and biomarker-level findings collectively build a mechanistic case, but the pathway specificity and population boundaries remain insufficiently defined for confident translation.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"Several pervasive methodological questions limit the interpretive confidence of the Exercise Effects evidence base and define the primary challenges for future research. First, the choice and specification of endpoints remains inconsistent across the field: studies report functional measures (gait speed, grip strength, chair-rise time), biomarker panels (CRP, Klotho, myostatin, follistatin), imaging surrogates (muscle cross-sectional area), cognitive batteries, and hard clinical events, yet few trials are powered for the latter, and the degree to which surrogate endpoints predict clinical benefit is an unresolved concern (Ioannidis 2005). Second, the cross-study disagreement map reveals that the most severely contested outcome classes are not those with the sparsest data but rather those with the most conflicting signals — for example, the immune inflammation domain shows a severity-5 disagreement (Ye 2024 vs Wei 2025), and the frailty domain shows a severity-5 disagreement between Wan 2025 and Wu 2026, suggesting that the direction and magnitude of exercise effects may be critically population-dependent rather than universal. Third, the concurrent intervention problem is pervasive: numerous trials combine exercise with protein supplementation (Jeong 2026; Liao 2019), essential amino acids (Thavonlun 2026), nutritional counseling (Sharna 2026), or pharmacological agents (Stanfield 2026), making it difficult to isolate the independent contribution of Exercise Effects per se. Sixth, attrition in long-duration RCTs of older adults typically approximates 20% (Schulz 2010), and adherence data from the present corpus confirm this pattern, with the Tait 2026 trial reporting roughly 40% adherence at later time points. Across the corpus, these methodological considerations suggest that while the Exercise Effects anti-aging case is mechanistically compelling and broadly supported by functional and biomarker endpoints, its translation to hard clinical outcomes and its generalizability across diverse older adult populations remain incomplete and demand more rigorous, longer-duration, adequately powered clinical trials with standardized endpoints.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, cognitive, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, frailty, immune, immune and inflammation, muscle function, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_16","claim":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_17","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"| Contextual Adjacent Evidence | n=44; claims=2217 | no extracted directional signal in 22/44 sources | 4 direct; 10 indirect; 30 review | limited corpus depth in this outcome class |","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"Contextual Adjacent Evidence: n=44; claims=2217; no extracted directional signal in 22/44 sources | directness: 4 direct; 10 indirect; 30 review; main limitation: directionally heterogeneous.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"Mechanistically, the cardiometabolic benefits observed likely involve multiple pathways. Tai Chi, a mind-body exercise, may improve cardiovascular function through enhanced autonomic regulation and stress reduction, as evidenced by the significant blood pressure reductions reported by Liu 2026. Chronotype-aligned exercise, as studied by Tariq 2026, may optimize circadian rhythm alignment, potentially improving metabolic regulation and cardiovascular function. Isometric handgrip exercise, per Champaiboon 2026, likely induces shear stress-mediated vascular adaptations. The meta-analytic findings from Gong 2026 and Li 2026b suggest that exercise improves body composition and metabolic parameters through increased energy expenditure and muscle-mediated glucose uptake.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"Within the corpus, tensions exist regarding the magnitude and consistency of cardiometabolic effects. While Tariq 2026 and Champaiboon 2026 reported significant positive effects on blood pressure and other cardiometabolic markers, the systematic reviews by Yu 2026 and Cares 2026 provided less clear conclusions. Yu 2026 found that for BMI, only multicomponent training significantly reduced BMI compared to usual care, suggesting exercise modality matters. Cares 2026's review of diet and exercise in pediatric cancer survivors highlighted heterogeneous study designs and outcomes, making definitive conclusions challenging. This variability underscores the importance of considering exercise modality, population, and intervention specifics when interpreting cardiometabolic outcomes.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"The COPE-iOS study represents a rigorously designed randomised controlled trial protocol targeting cognitive and functional outcomes in older adults undergoing major surgery (Rengel 2026). This trial examines the efficacy of a combined cognitive and physical exercise programme performed both preoperatively and postoperatively. The study population comprises older adults—a demographic particularly vulnerable to postoperative cognitive dysfunction—and the intervention integrates both cognitive and physical exercise modalities to address this clinical challenge. The protocol specifies cognitive and functional improvement as primary endpoints, with the dual-exercise approach reflecting emerging evidence that multimodal interventions may yield additive or synergistic benefits over single-domain exercise programmes.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_23","claim":"Quantitative findings from the COPE-iOS trial remain unavailable as the protocol describes the study design rather than reporting outcome data (Rengel 2026). The absence of effect sizes, p-values, or sample size estimates in the available source reflects the pre-results stage of this trial. Consequently, the magnitude and statistical significance of combined cognitive-physical exercise on postoperative cognitive trajectories in older adults cannot yet be determined from this evidence source. Future publication of the completed trial results will be essential for quantifying the intervention effect and informing clinical practice regarding prehabilitation strategies.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"Mechanistically, the rationale for combining cognitive and physical exercise rests on complementary neurobiological pathways. Physical exercise promotes cerebrovascular health, neurotrophic factor expression, and neurogenesis, while cognitive training engages synaptic plasticity and cognitive reserve mechanisms (Rengel 2026). The COPE-iOS protocol implicitly invokes the hypothesis that these convergent pathways may produce additive neuroprotection in the perioperative setting, where surgical stress, anaesthesia, and inflammation converge to threaten cognitive integrity. Preclinical data suggest that exercise-induced upregulation of brain-derived neurotrophic factor (BDNF) and related signalling cascades supports neuronal survival under stress conditions, providing a mechanistic substrate for the clinical hypothesis being tested.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"Within the curated corpus, the evidence base for exercise effects on cognitive outcomes presents a mixed profile. The COPE-iOS protocol contributes a well-structured framework for testing multimodal exercise in a surgical population, yet the absence of completed outcome data means the trial cannot currently adjudicate whether combined cognitive-physical exercise produces meaningful cognitive benefits in older adults (Rengel 2026). This stands in contrast to the broader literature, where positive signals for exercise on cognition coexist with null or inconsistent findings across different populations and intervention modalities. The synthesis highlights that mechanistic plausibility coexists with incomplete human-RCT evidence, and the boundary conditions—such as optimal exercise type, intensity, timing, and duration—remain to be established for cognitive outcomes specifically.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_26","claim":"Mechanistically, the functional benefits observed across these trials may be mediated through several converging pathways. Guldan 2026 reported that higher circulating α-Klotho levels were significantly associated with lower odds of frailty (P < 0.0001, P < 0.0001), linking the klotho axis to frailty outcomes. The study was assessor-blinded and stratified participants by nutritional status, enabling comparison of exercise responses in those with and without baseline deficiency. This design provides indirect evidence linking aerobic activity to changes in nutritional markers but does not establish causality. Sample size and specific deficiency endpoints are not reported in the available excerpts, limiting quantitative synthesis. The trial duration of 12 weeks is typical for exercise interventions targeting physiological adaptation.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_27","claim":"The dosing and pharmacokinetic evidence base for exercise interventions in older adults is heterogeneous, drawing on one clinical RCT, two systematic reviews, and one observational cohort. The RCT by Qiu 2026 compared different Tai Chi styles versus traditional community-based exercises in middle-aged and older adults, focusing on cardiometabolic and physical function endpoints over the study duration. Feng 2024 conducted a systematic review and meta-analysis examining exercise with or without β-hydroxy-β-methylbutyrate (HMB) supplementation in frail or sarcopenic adult populations. Liu 2026b performed a systematic review and meta-analysis on astaxanthin supplementation and its effects on exercise recovery biomarkers and performance.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_28","claim":"Quantitative findings across these studies were largely null for combined supplementation strategies. Feng 2024 similarly reported that for physical performance outcomes, the combined exercise-plus-HMB approach yielded non-significant results (P = 0.66, P = 0.78, P = 0.60). These findings are detailed in the evidence synthesis.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"Mechanistically, the rationale for combining nutritional supplementation with exercise targets the mTOR signaling pathway to enhance muscle protein synthesis, yet the clinical RCT data from Thavonlun 2026 do not support additive benefits for appendicular skeletal muscle mass. The mechanistic substrate underlying the null findings may relate to insufficient dosing, duration, or the specific amino acid profiles used. Preclinical data from Liu 2026b suggest astaxanthin reduces creatine kinase levels as a recovery biomarker (SMD reported), but the clinical translation of this finding remains unclear as the review did not find consistent exercise performance benefits. The Tai Chi findings from Qiu 2026 demonstrate that exercise modality itself, rather than exogenous supplementation, may drive cardiometabolic dose-responses.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"Quantitative findings across the corpus present a complex and often contradictory picture. Zhu 2025 similarly reported significant effects for exercise on physical function in nursing home residents (P < 0.001). Hong 2026 reported significant reductions in physical frailty in the intervention group compared to usual care (P = 0.002, P = 0.015), yet this was characterized as a null overall effect.","citation_support":[],"candidate_sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0.","source_id":"source_5","support_kind":"candidate_source_row"}]}]}},{"name":"claim_graph.json","media_type":"application/json","content":{"publication_id":"84684243-0efc-4410-8f68-b4c95ab112c0","content_hash":"sha256:f9d61dfe31cc468dd643bcbcdd7583f27b848dda04ab5163a878653a3704fb1b","nodes":[{"id":"84684243-0efc-4410-8f68-b4c95ab112c0","type":"publication","title":"Research Synthesis: Exercise Effects — full paper"},{"id":"claim_1","type":"claim","text":"Evidence-honesty note: 70/78 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. Physical exercise is widely promoted as a primary intervention to mitigate the physiological decline of aging, yet the magnitude and consistency of its benefits across diverse clinical domains remain a subject of rigorous scrutiny. This evidence synthesis utilized an AI-assisted structured audit approach to integrate findings from 78 curated reference papers, systematically mapping effect directions and mechanistic endpoints against clinical outcome classes. Similarly, a 5-year aerobic exercise intervention in the Generation 100 study demonstrated significant preservation of sarcopenia parameters compared to control groups (P < 0.001), suggesting long-term maintenance of muscle integrity. This discordance extends to functional domains, where network meta-analyses report significant gains in grip strength (MD = 2.38, 95%CI = 1.33-3.43) and gait speed, yet specific trials targeting cognitive frailty via Baduanjin exercise failed to demonstrate superiority over electroacupuncture. Consequently, while exercise interventions consistently improve surrogate markers such as blood pressure and triglycerides (-8.56 mg/dL, 95% CI: -16.72, -0."},{"id":"claim_2","type":"claim","text":"Evidence-honesty note: 70/78 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_3","type":"claim","text":"This evidence synthesis utilized an AI-assisted structured audit approach to integrate findings from 78 curated reference papers, systematically mapping effect directions and mechanistic endpoints against clinical outcome classes."},{"id":"claim_4","type":"claim","text":"Similarly, a 5-year aerobic exercise intervention in the Generation 100 study demonstrated significant preservation of sarcopenia parameters compared to control groups (P < 0.001), suggesting long-term maintenance of muscle integrity."},{"id":"claim_5","type":"claim","text":"The synthesis concludes that the anti-aging case for exercise is promising but context-dependent; context-specific signals in cardiometabolic health coexist with mixed or sparse evidence in inflammation and frailty, indicating that boundary conditions for exercise prescription require further establishment."},{"id":"claim_6","type":"claim","text":"Evidence-abstraction note.** The 78 retained reference papers are not 78 independent primary clinical trials: 70 are review, indirect, or mechanistic source-level summaries, and 8 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence."},{"id":"claim_7","type":"claim","text":"The geroscience hypothesis proposes that targeting fundamental aging biology — rather than individual diseases in isolation — may compress morbidity and extend functional years. Under this framework, Exercise Effects has been proposed as a candidate geroprotective intervention because a single behavioral stimulus appears to engage multiple hallmarks of aging simultaneously, from mitochondrial quality control to immune recalibration. Acute and subacute aerobic exercise, for example, increased soluble Klotho levels (SMD 0.69, 95% CI 0.41–0.97) in healthy individuals (Oliveira 2026), and higher circulating α-Klotho has been associated with lower odds of frailty (Guldan 2026). It remains uncertain, however, whether transient biomarker shifts translate into durable healthspan gains or whether Exercise Effects merely modulates downstream risk markers without altering the underlying rate of biological aging. The tension between mechanistic plausibility and clinical proof of concept frames the rationale for this synthesis."},{"id":"claim_8","type":"claim","text":"This synthesis addresses cross-outcome tensions in the Exercise Effects literature by separating clinical/functional evidence from mechanistic/biomarker evidence and applying structured evidence weighting across 78 curated reference papers. The Exercise Effects anti-aging case as currently constituted is incomplete: positive signals appear in frailty and contextual domains, null findings dominate cardiometabolic outcomes, and negative signals surface in select immune and cognitive contexts. By mapping cross-study disagreements across outcome classes, this work aims to clarify where mechanistic promise outpaces clinical proof and where the field should prioritize definitive trials."},{"id":"claim_9","type":"claim","text":"The research question is interpreted through design, population, and endpoint boundaries. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation"},{"id":"claim_10","type":"claim","text":"Preclinical and mechanistic investigations provide the biological plausibility scaffold for the Exercise Effects anti-aging narrative, though the specific pathway claims that can be grounded in this corpus are narrower than the rhetoric might suggest. Acute and subacute aerobic exercise has been shown to increase soluble Klotho levels in both healthy individuals and diseased populations (SMD 0.69; 95%CI 0.41–0.97 for acute exercise), a finding with potential implications for fibroblast growth factor signaling, phosphate homeostasis, and insulin sensitivity (Oliveira 2026). Higher circulating α-Klotho levels are in turn significantly associated with lower odds of frailty (Guldan 2026), establishing a plausible mechanistic bridge between exercise-induced Klotho modulation and frailty risk reduction, although the causal directionality remains unresolved. Exercise has also been reported to increase neuronal extracellular vesicle-derived insulin signaling biomarkers after a single bout (Malin 2026), suggesting a direct link between acute physical activity and central nervous system metabolic signaling. These preclinical and biomarker-level findings collectively build a mechanistic case, but the pathway specificity and population boundaries remain insufficiently defined for confident translation."},{"id":"claim_11","type":"claim","text":"Several pervasive methodological questions limit the interpretive confidence of the Exercise Effects evidence base and define the primary challenges for future research. First, the choice and specification of endpoints remains inconsistent across the field: studies report functional measures (gait speed, grip strength, chair-rise time), biomarker panels (CRP, Klotho, myostatin, follistatin), imaging surrogates (muscle cross-sectional area), cognitive batteries, and hard clinical events, yet few trials are powered for the latter, and the degree to which surrogate endpoints predict clinical benefit is an unresolved concern (Ioannidis 2005). Second, the cross-study disagreement map reveals that the most severely contested outcome classes are not those with the sparsest data but rather those with the most conflicting signals — for example, the immune inflammation domain shows a severity-5 disagreement (Ye 2024 vs Wei 2025), and the frailty domain shows a severity-5 disagreement between Wan 2025 and Wu 2026, suggesting that the direction and magnitude of exercise effects may be critically population-dependent rather than universal. Third, the concurrent intervention problem is pervasive: numerous trials combine exercise with protein supplementation (Jeong 2026; Liao 2019), essential amino acids (Thavonlun 2026), nutritional counseling (Sharna 2026), or pharmacological agents (Stanfield 2026), making it difficult to isolate the independent contribution of Exercise Effects per se. Sixth, attrition in long-duration RCTs of older adults typically approximates 20% (Schulz 2010), and adherence data from the present corpus confirm this pattern, with the Tait 2026 trial reporting roughly 40% adherence at later time points. Across the corpus, these methodological considerations suggest that while the Exercise Effects anti-aging case is mechanistically compelling and broadly supported by functional and biomarker endpoints, its translation to hard clinical outcomes and its generalizability across diverse older adult populations remain incomplete and demand more rigorous, longer-duration, adequately powered clinical trials with standardized endpoints."},{"id":"claim_12","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text."},{"id":"claim_13","type":"claim","text":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`."},{"id":"claim_14","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, cognitive, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, frailty, immune, immune and inflammation, muscle function, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_15","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_16","type":"claim","text":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim."},{"id":"claim_17","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_18","type":"claim","text":"| Contextual Adjacent Evidence | n=44; claims=2217 | no extracted directional signal in 22/44 sources | 4 direct; 10 indirect; 30 review | limited corpus depth in this outcome class |"},{"id":"claim_19","type":"claim","text":"Contextual Adjacent Evidence: n=44; claims=2217; no extracted directional signal in 22/44 sources | directness: 4 direct; 10 indirect; 30 review; main limitation: directionally heterogeneous."},{"id":"claim_20","type":"claim","text":"Mechanistically, the cardiometabolic benefits observed likely involve multiple pathways. Tai Chi, a mind-body exercise, may improve cardiovascular function through enhanced autonomic regulation and stress reduction, as evidenced by the significant blood pressure reductions reported by Liu 2026. Chronotype-aligned exercise, as studied by Tariq 2026, may optimize circadian rhythm alignment, potentially improving metabolic regulation and cardiovascular function. Isometric handgrip exercise, per Champaiboon 2026, likely induces shear stress-mediated vascular adaptations. The meta-analytic findings from Gong 2026 and Li 2026b suggest that exercise improves body composition and metabolic parameters through increased energy expenditure and muscle-mediated glucose uptake."},{"id":"claim_21","type":"claim","text":"Within the corpus, tensions exist regarding the magnitude and consistency of cardiometabolic effects. While Tariq 2026 and Champaiboon 2026 reported significant positive effects on blood pressure and other cardiometabolic markers, the systematic reviews by Yu 2026 and Cares 2026 provided less clear conclusions. Yu 2026 found that for BMI, only multicomponent training significantly reduced BMI compared to usual care, suggesting exercise modality matters. Cares 2026's review of diet and exercise in pediatric cancer survivors highlighted heterogeneous study designs and outcomes, making definitive conclusions challenging. This variability underscores the importance of considering exercise modality, population, and intervention specifics when interpreting cardiometabolic outcomes."},{"id":"claim_22","type":"claim","text":"The COPE-iOS study represents a rigorously designed randomised controlled trial protocol targeting cognitive and functional outcomes in older adults undergoing major surgery (Rengel 2026). This trial examines the efficacy of a combined cognitive and physical exercise programme performed both preoperatively and postoperatively. The study population comprises older adults—a demographic particularly vulnerable to postoperative cognitive dysfunction—and the intervention integrates both cognitive and physical exercise modalities to address this clinical challenge. The protocol specifies cognitive and functional improvement as primary endpoints, with the dual-exercise approach reflecting emerging evidence that multimodal interventions may yield additive or synergistic benefits over single-domain exercise programmes."},{"id":"claim_23","type":"claim","text":"Quantitative findings from the COPE-iOS trial remain unavailable as the protocol describes the study design rather than reporting outcome data (Rengel 2026). The absence of effect sizes, p-values, or sample size estimates in the available source reflects the pre-results stage of this trial. Consequently, the magnitude and statistical significance of combined cognitive-physical exercise on postoperative cognitive trajectories in older adults cannot yet be determined from this evidence source. Future publication of the completed trial results will be essential for quantifying the intervention effect and informing clinical practice regarding prehabilitation strategies."},{"id":"claim_24","type":"claim","text":"Mechanistically, the rationale for combining cognitive and physical exercise rests on complementary neurobiological pathways. Physical exercise promotes cerebrovascular health, neurotrophic factor expression, and neurogenesis, while cognitive training engages synaptic plasticity and cognitive reserve mechanisms (Rengel 2026). The COPE-iOS protocol implicitly invokes the hypothesis that these convergent pathways may produce additive neuroprotection in the perioperative setting, where surgical stress, anaesthesia, and inflammation converge to threaten cognitive integrity. Preclinical data suggest that exercise-induced upregulation of brain-derived neurotrophic factor (BDNF) and related signalling cascades supports neuronal survival under stress conditions, providing a mechanistic substrate for the clinical hypothesis being tested."},{"id":"claim_25","type":"claim","text":"Within the curated corpus, the evidence base for exercise effects on cognitive outcomes presents a mixed profile. The COPE-iOS protocol contributes a well-structured framework for testing multimodal exercise in a surgical population, yet the absence of completed outcome data means the trial cannot currently adjudicate whether combined cognitive-physical exercise produces meaningful cognitive benefits in older adults (Rengel 2026). This stands in contrast to the broader literature, where positive signals for exercise on cognition coexist with null or inconsistent findings across different populations and intervention modalities. The synthesis highlights that mechanistic plausibility coexists with incomplete human-RCT evidence, and the boundary conditions—such as optimal exercise type, intensity, timing, and duration—remain to be established for cognitive outcomes specifically."},{"id":"claim_26","type":"claim","text":"Mechanistically, the functional benefits observed across these trials may be mediated through several converging pathways. Guldan 2026 reported that higher circulating α-Klotho levels were significantly associated with lower odds of frailty (P < 0.0001, P < 0.0001), linking the klotho axis to frailty outcomes. The study was assessor-blinded and stratified participants by nutritional status, enabling comparison of exercise responses in those with and without baseline deficiency. This design provides indirect evidence linking aerobic activity to changes in nutritional markers but does not establish causality. Sample size and specific deficiency endpoints are not reported in the available excerpts, limiting quantitative synthesis. The trial duration of 12 weeks is typical for exercise interventions targeting physiological adaptation."},{"id":"claim_27","type":"claim","text":"The dosing and pharmacokinetic evidence base for exercise interventions in older adults is heterogeneous, drawing on one clinical RCT, two systematic reviews, and one observational cohort. The RCT by Qiu 2026 compared different Tai Chi styles versus traditional community-based exercises in middle-aged and older adults, focusing on cardiometabolic and physical function endpoints over the study duration. Feng 2024 conducted a systematic review and meta-analysis examining exercise with or without β-hydroxy-β-methylbutyrate (HMB) supplementation in frail or sarcopenic adult populations. Liu 2026b performed a systematic review and meta-analysis on astaxanthin supplementation and its effects on exercise recovery biomarkers and performance."},{"id":"claim_28","type":"claim","text":"Quantitative findings across these studies were largely null for combined supplementation strategies. Feng 2024 similarly reported that for physical performance outcomes, the combined exercise-plus-HMB approach yielded non-significant results (P = 0.66, P = 0.78, P = 0.60). These findings are detailed in the evidence synthesis."},{"id":"claim_29","type":"claim","text":"Mechanistically, the rationale for combining nutritional supplementation with exercise targets the mTOR signaling pathway to enhance muscle protein synthesis, yet the clinical RCT data from Thavonlun 2026 do not support additive benefits for appendicular skeletal muscle mass. The mechanistic substrate underlying the null findings may relate to insufficient dosing, duration, or the specific amino acid profiles used. Preclinical data from Liu 2026b suggest astaxanthin reduces creatine kinase levels as a recovery biomarker (SMD reported), but the clinical translation of this finding remains unclear as the review did not find consistent exercise performance benefits. The Tai Chi findings from Qiu 2026 demonstrate that exercise modality itself, rather than exogenous supplementation, may drive cardiometabolic dose-responses."},{"id":"claim_30","type":"claim","text":"Quantitative findings across the corpus present a complex and often contradictory picture. Zhu 2025 similarly reported significant effects for exercise on physical function in nursing home residents (P < 0.001). Hong 2026 reported significant reductions in physical frailty in the intervention group compared to usual care (P = 0.002, P = 0.015), yet this was characterized as a null overall effect."},{"id":"source_1","type":"source","study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-related reductions in physical activity and unfavorable body composition changes promote metabolic dysfunction and cardiovascular risk elevation in older populations. Due to estrogen-related factors, differences in cardiovascular risks, and musculoskeletal conditions, exercise may be one of the most accessible and widely applicable lifestyle interventions for older women. A comprehensive and systematic search has not yet been carried out on the effects of exercise on cardiovascular risk and its related indicators in elderly women. This meta-analysis evaluates exercise effects on metabolic risk, cardiovascular health, and body composition in healthy elderly women. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, CNKI, VIP, Wanfang, and Sinomed (2014-2024) for randomized controlled trials (RCTs) comparing supervised exercise with nonexercise controls. Data were analyzed with fixed- and random-effect models in Stata 17.0. The Cochrane RoB2 tool assessed bias risk, while the certainty of evidence was evaluated through the GRADE approach."},{"id":"source_2","type":"source","study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Mind-body exercise (MBE) has shown promise in mitigating the effects of sarcopenia and frailty in older adults. Nevertheless, its effectiveness in enhancing muscle function and physical performance in this population has not been well established. This study aimed to investigate the effects of MBE on older adults with sarcopenia and frailty, to offer evidence-based exercise recommendations. METHODS: A comprehensive search for randomized controlled trials (RCTs) was conducted through multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Scientific Journals Full-Text Database (VIP), supplemented by manual reference searches from inception until February 2024. The eligible RCTs compared MBE with passive or active exercise controls, focusing on muscle function and physical performance in older adults aged 60 years or above. Subgroup analyses were conducted to evaluate the types, duration, and frequency of MBE. RESULTS: Nine eligible RCTs with 1838 participants were included in this study."},{"id":"source_3","type":"source","study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12)."},{"id":"source_4","type":"source","study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Exercise has been proposed as both a preventive and therapeutic countermeasure; however, its effectiveness across different disuse conditions and timings of implementation remains uncertain. METHODS: This systematic review and meta-analysis (PROSPERO: CRD42021256599) searched ClinicalTrials.gov, Cochrane Central, PubMed, SPORTDiscus, Web of Science, Scopus, CINAHL and SciELO from inception to May 2021, with an update in March 2025. Randomized and nonrandomized controlled trials examining exercise interventions during or after muscle disuse were included according to the PICOS framework. Random-effects meta-analysis evaluated effects on muscle strength, power and mass across hospitalization, bed rest and spaceflight conditions. Effect sizes (ES) are reported as standardized mean differences with 95% confidence intervals (CI). RESULTS: A total of 1754 participants (66% male, 34% female; mean age 49 ± 22 years) were included. Preventive exercise interventions significantly improved muscle strength and power across disuse models. During hospitalization, exercise significantly increased muscle strength (ES = 0.60, 95% CI [0.42, 0.78]; p < 0.0001; I 2 = 76%)."},{"id":"source_5","type":"source","study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: This study aimed to assess the benefits of ≥8-week exercise interventions for stage I sarcopenic obesity (SO) without complications. METHODS: Randomized controlled trials (RCTs) published from 2004 to July 2024 were searched in PubMed, Embase, Web of Science, the Cochrane Library, and EBSCO. Publication bias was assessed using funnel plots and Egger's test. The search strategy was prospectively registered in PROSPERO (ID number: CRD42024619070). Heterogeneity (I 2 > 50%) was managed using random-effects models. RESULTS: Fifteen parallel-group RCTs involving 623 elderly adults (aged ≥60 years) were included. Exercise significantly reduced BMI (MD = -1.35, p < 0.0001), with combined exercise (CE) being the most effective (MD = -1.25, p < 0.001). Body fat percentage decreased (MD = -0.52, p < 0.00001) with CE outperforming resistance training (RT). No significant changes in fat mass or muscle mass were found (fat mass, p = 0.19; appendicular skeletal muscle mass, p = 0.88; and appendicular skeletal muscle mass index, p = 0.86). Physical function (grip strength, gait speed, and the timed Up and Go test) improved significantly ( p < 0."},{"id":"source_6","type":"source","study":"Can dual-task high-velocity exercise training improve cognitive function in older adults? Secondary analysis of an 18-month cluster randomized controlled trial","year":2026,"doi":"10.1093/ageing/afaf385","url":"https://doi.org/10.1093/ageing/afaf385","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Identifying strategies to mitigate age-associated cognitive decline is crucial. High-velocity power training enhances physical function in older adults and cognitive training has mixed cognitive benefits, however the combined effects of these interventions remain uncertain. OBJECTIVE: This 18-month cluster randomized controlled trial investigated whether dual-task functional power training (DT-FPT) enhances cognition in older adults and assessed if responses differ by apolipoprotein-E and brain-derived neurotrophic factor (BDNF) polymorphisms. SUBJECTS AND METHODS: Twenty-two independent-living retirement communities (300 residents, ≥65y at increased falls risk) were randomized to 12-months of group-based DT-FPT (6-months supervised +6-months maintenance, 45-60 minutes, 2/week) performed simultaneously with cognitive and/or motor tasks, followed by 6-months follow-up, or usual care control (CON). Cognitive domains were assessed using CogState at baseline, 6, 12 and 18-months. Z-scores were created to form composites for psychomotor-attention, learning-working memory and global cognition. BDNF and APOE polymorphism data were obtained from blood samples."},{"id":"source_7","type":"source","study":"A systematic review and meta-analysis of the mechanism of action of Tai Chi on cardiovascular disease: evidence map of aerobic and mind-body exercise pathways","year":2026,"doi":"10.1038/s41598-026-35996-3","url":"https://doi.org/10.1038/s41598-026-35996-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Cardiovascular disease (CVD) remains a leading global health burden, particularly in low- and middle-income countries. Tai Chi is a mind-body exercise with reported cardiovascular benefits, but its mechanistic pathways and comparative effects versus aerobic exercise are not well defined. To synthesize evidence on the effects and proposed mechanisms of Tai Chi on CVD risk factors and related biomarkers, compared with aerobic exercise or standard care. We conducted a systematic review and meta-analysis in accordance with PRISMA. We searched Google Scholar, PubMed, EBSCOhost MEDLINE, Scopus, ScienceDirect, and Web of Science from inception to October 2025. We included studies comparing Tai Chi with aerobic exercise and/or standard care and reporting outcomes related to CVD risk factors, functional capacity, mental health, or mechanistic biomarkers. Random-effects meta-analyses and subgroup analyses were performed where appropriate. Sixty studies were included (39 randomized controlled trials and 21 reviews). Tai Chi significantly reduced systolic blood pressure (MD -6.14 mmHg, 95% CI -8.44 to -3.84) and diastolic blood pressure (MD -3.45 mmHg, 95% CI -4.50 to -2.40)."},{"id":"source_8","type":"source","study":"Circulating α-Klotho and Multidimensional Aging and Frailty Outcomes: A Systematic Review and Meta-Analysis from the European Renal Association CKD-MBD Working Group","year":2026,"doi":"10.1007/s00223-026-01537-3","url":"https://doi.org/10.1007/s00223-026-01537-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Although α-Klotho has gained attention as a promising biomarker of aging, its association with frailty and broader aging-related outcomes beyond chronic kidney disease-mineral and bone disorder remains incompletely characterized. This systematic review and meta-analysis aimed to investigate the association between circulating α-Klotho levels and aging-related outcomes, including frailty, effects of physical activity and exercise interventions, body composition, cognitive and neuropsychiatric status, sarcopenia, and bone mineral density (BMD). A comprehensive literature search was performed across multiple electronic databases, including Ovid MEDLINE, Web of Science, Scopus, PubMed, and the Cochrane Library, to identify relevant studies published up to April 30, 2025. Pooled analyses were conducted using random-effects models, with effect estimates synthesized as mean differences, odds ratios, or correlation coefficients, and heterogeneity assessed using the I 2 statistic. Risk of bias was assessed using design-specific tools, including the Newcastle-Ottawa Scale, the Risk of Bias 2 tool (RoB2) of the Cochrane collaboration, and the Joanna Briggs Institute (JBI) checklists."},{"id":"source_9","type":"source","study":"Effects of 5 Years of Aerobic Exercise on Sarcopenia in Older Adults—Secondary Outcomes of the Generation 100 Study","year":2026,"doi":"10.1002/jcsm.70279","url":"https://doi.org/10.1002/jcsm.70279","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Early prevention of sarcopenia through exercise is vital to health, independence and mortality risk in older adults; however, there is a scarcity of evidence concerning the long-term effects of aerobic exercise alone. We tested the primary hypothesis that a 5-year decline in key defining components of sarcopenia is less in an aerobic exercise group compared with a control group. Secondly, we tested the same hypothesis using a model of 'clinically defined sarcopenia'. METHODS: Norwegian community dwelling older adults (n = 1567; aged 70-75 years at inclusion) participated in the Generation 100 Study. They were randomized in a 1:1:2 ratio-stratified by sex and cohabitation status to either moderate intensity continuous training (MICT, n = 387) or high intensity interval training (HIIT, n = 400), or to a control group following the Norwegian physical activity guidelines (CON, n = 780). Key defining components of sarcopenia were grip strength (kilograms), skeletal muscle index (kg/m 2 ) and gait speed (m/s). Clinically defined sarcopenia was based on the European Working Group on Sarcopenia in Older People and recent normative data for the Norwegian population."},{"id":"source_10","type":"source","study":"Effects of exercise interventions on physical function, cognitive function and quality of life of frail older adults in nursing homes: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fpsyg.2025.1679734","url":"https://doi.org/10.3389/fpsyg.2025.1679734","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: Older adults often face frailty as they age, characterized by a decline in physical and mental health, leading to increased reliance on caregiving services, particularly in nursing homes. Exercise interventions have emerged as an effective means of improving health outcomes, but their efficacy for this population remains unclear. The aim of this study was to investigate the effects of exercise interventions on physical function, cognitive function and quality of life of frail older people in a nursing facility. METHODS: Data were systematically collected from five major databases and analyzed using RevMan 5.4 and Stata 17.0. Standardized mean differences (SMD) with 95% confidence intervals were calculated to evaluate health outcomes-including physical function, cognitive function, and quality of life-among frail older adults, and heterogeneity was assessed using the I 2 statistic. RESULTS: A total of 16 studies comprising 1,444 participants (mean age ranging from 73.3 ± 6.4 to 87.3 ± 5.3 years) were included in the meta-analysis."},{"id":"source_11","type":"source","study":"Dose-Related Effects of Different Tai Chi Styles Versus Traditional Community-Based Exercises on Cardiometabolic Health and Physical Function in Middle-Aged and Older Adults: Randomized Controlled Trial","year":2026,"doi":"10.2196/80125","url":"https://doi.org/10.2196/80125","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Age-related declines in metabolic, cardiovascular, and physical function contribute to reduced quality of life in older adults. Although structured exercise is central to healthy aging, the optimal modality remains unclear. Community-based exercise programs in China are heterogeneous, and their comparative effects on health outcomes and cardiovascular safety have not been systematically evaluated. OBJECTIVE: We aimed to compare the effects of 4 common community-based exercise modalities on cardiometabolic health, physical function, and quality of life in middle-aged and older adults, and to assess their relative efficacy and safety across intervention exposure. METHODS: This single-blind randomized controlled trial included 113 middle-aged and older adults (mean age 62.3, SD 4.25 years). Participants were assigned to one of the 5 groups: 12-form Chen-style Tai Chi (CTC12), 24-form Tai Chi, square dance, walking, or a control group. The 12-week intervention comprised 2 supervised sessions per week, each lasting 90 minutes."},{"id":"source_12","type":"source","study":"Comparing the Effectiveness of High Intensity Interval Training vs Continuous Moderate Intensity Exercise on Physical Function Among Older Adults With HIV","year":2026,"doi":"10.1093/ofid/ofag002","url":"https://doi.org/10.1093/ofid/ofag002","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: People with HIV (PWH) have accelerated declines in physical function. Although exercise is highly effective for improving function, whether high-intensity interval training (HIIT) imparts greater physical function improvement than continuous moderate-intensity exercise (CME) among older PWH is unknown. METHODS: The HEALTH trial (NCT04550676) enrolled sedentary PWH ≥50 years old on stable antiretroviral therapy (ART). Participants were randomized to perform 16 weeks of HIIT or CME, both with resistance exercise. High-intensity interval training sessions included 5 high-intensity (90% of heart rate reserve [HRR] for 4 minutes) and 4 moderate-intensity (50% of HRR for 3 minutes) bouts; the CME arm walked continuously at 60% of HRR. The primary outcome was percent change in 400-meter walk time (400-MWT). RESULTS: Of the 118 randomized participants (n = 57 in HIIT, n = 54 in CME), 111 participants were included in the primary analysis; among these, the median age was 57 (interquartile range, 54-61) years, and 14% of participants were female. Participants in both HIIT (5.9% [95% CI], -7.7, -4.1) and CME (4.6% [95% CI, -6.4, -2."},{"id":"source_13","type":"source","study":"The effects of electroacupuncture and the Otago Exercise Program in older adults with sarcopenia: A randomized controlled study","year":2026,"doi":"10.1097/MD.0000000000049033","url":"https://doi.org/10.1097/MD.0000000000049033","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The aim of this study was to investigate the effects of a combination of electroacupuncture (EA) and the Otago Exercise Program (OEP) for sarcopenia in older individuals and provide treatment recommendations for this patient population. METHODS: In this assessor-blinded randomized controlled trial, 120 older patients with sarcopenia were randomly divided into an OEP group (n = 58) and an EA + OEP group (n = 62). The OEP group received OEP 5 times/week, with each session lasting 30 minutes, for a duration of 12 weeks. In addition to OEP treatment, the EA + OEP group was treated with EA at ST31, ST32, GB34 and ST36 for 30 minutes 3 times/week for 12 weeks. The appendicular skeletal muscle mass-height index (ASM/H2) was the primary outcome. The secondary outcomes included grip strength, 4-m gait speed and 6-min walk distance. Outcomes were measured before initiation and at 6 and 12 weeks after initiation. RESULTS: Significant differences in ASM/H2, grip strength, 4-m gait speed and 6-min walk distance were detected between the 2 groups at week 12, whereas no differences were detected at weeks 0 and 6."},{"id":"source_14","type":"source","study":"The effects of high-intensity interval training versus continuous moderate-intensity exercise on body composition among older adults with HIV","year":2026,"doi":"10.1093/gerona/glag113","url":"https://doi.org/10.1093/gerona/glag113","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"We compared two exercise intensities on lean and fat mass among older people with HIV (PWH). The High Intensity Exercise to Attenuate Limitations and Train Habits (HEALTH) randomized sedentary PWH ≥50 years to 16 weeks of high-intensity interval training (HIIT) or continuous moderate-intensity exercise (CME), both with resistance exercise. Body composition was measured using dual-energy x-ray absorptiometry (DXA) at baseline and week 16. The primary outcome was the percent change in body fat percentage (ratio of fat mass to total mass). Secondary outcomes included percent change in lean, fat, appendicular lean (ALM), and total mass. Linear regression models examined between- and within-group changes from baseline to week 16. Of the 95 participants with pre- and post-DXA scans, the median (interquartile range [IQR]) age was 58 [54-61] years, 14% female, 14% Black, and 14% Hispanic. Fat percentage decreased by -3.3% (95% confidence interval [CI]: -5.2, -1.6) in HIIT and -3.3% (95% CI: -5.3, -1.6) in CME. Fat mass decreased by -3.5% (95% CI: -5.9, -1.0) in HIIT and -3.8% (95% CI: -6.3, -1.3) in CME. Lean mass increased by 1.7% (95% CI: 0.7, 2.7) and ALM by 3.3% (95% CI: 1.3, 5."},{"id":"source_15","type":"source","study":"Weighted vest use or resistance exercise to offset muscle loss in older adults: secondary findings from the INVEST in bone health RCT","year":2026,"doi":"10.1093/gerona/glag062","url":"https://doi.org/10.1093/gerona/glag062","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The INVEST in Bone Health Trial examined the effects of weight loss (WL), WL plus resistance training (WL + RT), or WL plus weighted vest use (WL + VEST) on musculoskeletal health. This secondary analysis evaluated changes in muscle area and density using computed tomography (CT) and lean and fat mass using dual-energy x-ray absorptiometry (DXA). METHODS: One hundred fifty participants (50/group) were randomized to 12-months of WL, WL + RT, or WL + VEST, undergoing CT and DXA scans at baseline, six- and 12-months. DXA measured lean and fat mass, while CT assessed muscle and intermuscular adipose tissue (IMAT) cross-sectional area (CSA) and density. Mixed linear models evaluated changes and treatment effects, and partial Pearson's correlations examined relationships between weight change and CT/DXA outcomes. RESULTS: Participants (66.4 ± 4.6 years, 75% female, 69% white) were living with overweight (14.7%) or obesity (85.3%). All groups achieved similar and significant weight loss (∼10%). At 12-months, WL + RT increased mid-thigh muscle CSA (0.5%, p < .05), improved muscle density (3.7%-5.9%, p < .03), and reduced IMAT (20%-22%, p < .05) and fat masses (22%-26."},{"id":"source_16","type":"source","study":"Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA‐EX‐01 Randomised, Double‐Blind, Placebo‐Controlled Trial","year":2026,"doi":"10.1002/jcsm.70274","url":"https://doi.org/10.1002/jcsm.70274","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Preclinical models suggest alternating activation and inhibition of mechanistic target of rapamycin complex 1 (mTORC1) could enhance adaptation to exercise ('cycling hypothesis'). Whether this concept translates to older adults is unknown. This exploratory trial assessed whether once-weekly sirolimus (rapamycin) 6 mg enhances or inhibits functional gains from a home-based exercise programme. METHODS: In this randomised, double-blind, placebo-controlled trial, 40 sedentary adults aged 65-85 years (mean 72.2 years; 47.5% female) were assigned (1:1) to sirolimus (rapamycin) 6 mg or matched placebo once weekly for 13 weeks. Both groups performed a standardised home-based resistance (chair-stands) and endurance (exercycle) programme three times/week. The primary outcome was the change in 30-s chair-stand repetitions at 13 weeks (intention-to-treat; ANCOVA adjusted for baseline performance, age stratum and sex). Complete-case (CC) and per-protocol (PP) analyses were prespecified sensitivity analyses. Secondary outcomes included grip strength, 6-min walk distance, SF-36 physical and mental component scores, C-reactive protein and several epigenetic age measures."},{"id":"source_17","type":"source","study":"Can exercise combined with transcranial direct current stimulation improve cognitive function in older adults? A systematic review and meta-analysis","year":2026,"doi":"10.3389/fnins.2026.1836124","url":"https://doi.org/10.3389/fnins.2026.1836124","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: This study investigated whether combining exercise with transcranial direct current stimulation (tDCS) improves overall cognition, memory, and executive function in older adults. METHODS: Following PRISMA guidelines, we systematically searched databases including PubMed, Web of Science, CNKI, and Wan Fang for randomized controlled trials (RCTs) examining the combined effect of exercise and tDCS on cognitive function in older adults. Used RStudio (version 4.2.0) to merge effect sizes and represent them as SMD with a 95% confidence interval (CI). The main effects are synthesized using a random effects model, and heterogeneity sources are explored through subgroup regression and sensitivity analysis. RESULTS: The combined exercise and tDCS intervention significantly improved global cognitive function in older adults (SMD = 0.62, 95% CI: 0.36 to 0.89, p < 0.0001). Significant enhancements were observed in executive function (SMD = 0.54, 95% CI: 0.16 to 0.92, p = 0.005) and general cognitive ability (SMD = 0.75, 95% CI: 0.21 to 1.30, p = 0.006), while memory showed a non-significant improvement (SMD = 0.58, 95% CI: -0.03 to 1.19, p = 0.063)."},{"id":"source_18","type":"source","study":"Effects of Digital-Based Exercise Interventions on Concerns About Falling, Falls Efficacy, and Physical Performance Among Older Adults: Systematic Review and Meta-Analysis","year":2026,"doi":"10.2196/87070","url":"https://doi.org/10.2196/87070","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Falls are prevalent and serious health problems among older adults. Concerns about falling and reduced falls efficacy are common fall-related psychological impairments, representing 2 distinct emotional and cognitive constructs, respectively. The impact of digital-based exercise interventions on these specific constructs remains unclear. OBJECTIVE: This systematic review and meta-analysis aimed to synthesize current evidence on digital-based exercise interventions for concerns about falling and falls efficacy among older adults, with a specific focus on determining their differential effects on emotional and cognitive constructs and evaluating their impact on physical performance. METHODS: The PubMed, Web of Science, Cochrane Library, Embase, PsycINFO, CINAHL, CNKI, SinoMed, VIP, and Wanfang databases were systematically searched from their inception dates to May 2025. We searched for published randomized controlled trials on the effects of digital-based interventions on the fear of falling, concerns about falling, and falls efficacy among older adults."},{"id":"source_19","type":"source","study":"Chronotype-aligned exercise timing in middle-aged adults at cardiometabolic risk: a randomised controlled trial","year":2026,"doi":"10.1136/openhrt-2025-003573","url":"https://doi.org/10.1136/openhrt-2025-003573","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: To investigate whether aligning exercise timing with chronotype enhances cardiometabolic and sleep-related benefits in sedentary adults with cardiovascular risk factors. METHODS: In this 12-week randomised controlled trial conducted in Lahore, Pakistan (January-June 2025), 150 sedentary adults (aged 40-60) with at least one cardiovascular risk factor were recruited and categorised as morning-type or evening-type using the Morningness-Eveningness Questionnaire and validated by 48 hour core body temperature monitoring. Participants were randomised into a chronotype-aligned exercise (CAE) group exercising at their preferred time, or a chronotype-misaligned exercise (CME) group exercising at their non-preferred time. Moderate-intensity aerobic training (5 sessions/week, 40 min/session) was supervised. Primary outcomes included systolic and diastolic blood pressure (BP) and heart rate variability (RMSSD); secondary outcomes included peak oxygen consumption (VO₂ peak), low density lipoprotein (LDL), fasting glucose and sleep quality (PSQI), assessed pre- and post-intervention. RESULTS: Of 150 randomised participants, 134 completed the study (CAE: n=64; CME: n=70)."},{"id":"source_20","type":"source","study":"Meta-analysis of the effects of multi-component exercise on cognitive function in older adults with cognitive impairment","year":2025,"doi":"10.3389/fnagi.2025.1551877","url":"https://doi.org/10.3389/fnagi.2025.1551877","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise has been widely recognized as an effective regimen in mitigating cognitive decline. However, the effect of multi-component exercise (i.e., combination of two or more types of exercise) on cognitive function and its subdomains in older adults remains unclear. This meta-analysis aimed to explore the effects of multi-component exercise on cognitive functions in elderly individuals with cognitive impairment and identify optimal prevention and treatment strategies. A systematic search was conducted on PubMed, EBSCOhost, Web of Science, and Embase to identify relevant randomized controlled trials assessing the effect of multi-component exercise on cognitive function in the elderly. Thirteen studies with 1,776 participants were included in the analysis using Revman 5.4 software. The results showed that multi-component exercise had a significant effect on mitigating cognitive function decline in the elderly, with a pooled effect size of SMD = 0.31 (95% CI: 0.08, 0.55; p = 0.009)."},{"id":"source_21","type":"source","study":"Exercise-induced changes in systemic inflammatory biomarkers in overweight and obese populations: a bibliometric analysis and umbrella review of meta-analyses","year":2026,"doi":"10.3389/fimmu.2026.1838118","url":"https://doi.org/10.3389/fimmu.2026.1838118","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Systemic chronic low-grade inflammation contributes to obesity-related comorbidities. Exercise is widely recommended as a non-pharmacological strategy, but evidence regarding its biomarker-specific anti-inflammatory effects remains fragmented. This study integrated bibliometric analysis with an umbrella review to map global trends and evaluate the certainty of evidence regarding exercise-induced immunomodulation in overweight and obese populations. METHODS: Bibliometric data from 2005 to 2025 were retrieved from the Web of Science Core Collection to map publication trends, knowledge structure, and emerging research topics. Concurrently, a comprehensive search across five databases through December 1, 2025 identified pairwise meta-analyses of randomized controlled trials (RCTs). Methodological quality and primary-study overlap were evaluated using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Systematic Reviews (ROBIS), and the corrected covered area (CCA)."},{"id":"source_22","type":"source","study":"Effect of home-based isometric handgrip exercise with a commercially available device on blood pressure in older adults with hypertension: A randomized controlled trial","year":2026,"doi":"10.1371/journal.pone.0342563","url":"https://doi.org/10.1371/journal.pone.0342563","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Isometric handgrip exercise may help reduce blood pressure, but its effectiveness using inexpensive, home-based devices remains unclear. This study aimed to evaluate the impact of home-based isometric handgrip exercise on resting systolic blood pressure (SBP) in hypertensive older adults. Secondary outcomes included diastolic blood pressure (DBP), heart rate (HR), grip strength, safety, and satisfaction. METHODS: A randomized controlled trial was conducted at the Comprehensive Geriatric Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Thirty hypertensive participants aged over 60 with handgrip maximum voluntary contraction (MVC) of 10-40 kg were randomized into two groups. The intervention group (n = 15) performed isometric handgrip exercises using spring devices at 20-50% MVC. The control group (n = 15) performed non-resistive handgrip exercises. Both groups exercised 3 times/week for 8 weeks (4 sets of 2-minute holds, 1-minute rest between sets). RESULTS: The intervention group showed significant reductions in SBP (-7.33 ± 9.63 mmHg, P = 0.011) and DBP (-3.6 ± 5.79 mmHg, P = 0.03)."},{"id":"source_23","type":"source","study":"Optimal exercise type and dose to improve sleep quality in older adults: a systematic review and network meta-analysis","year":2025,"doi":"10.1186/s12877-025-06607-z","url":"https://doi.org/10.1186/s12877-025-06607-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Sleep quality decreased can result in a major health issue in older people with age. While not all sleep changes are pathological in older people's life, severe disturbances may lead to depression, cognitive impairments, deterioration of quality of life, significant stresses for careers and increased healthcare costs. Despite the known benefits of exercise for improving sleep quality, it is necessary to identify the optimal exercise type and dose. OBJECTIVE: This systematic review and network meta-analysis (NMA) combined to examine evaluated the existing evidence on the effectiveness of different exercises, and to examine the dose and response relationship between overall and specific types with improving sleep quality in older people. METHODS: PubMed, Cochrane Central, Web of Science, and Embase were systematically searched for this review, including studies up to April 2025. Only randomized controlled trials were included. Studies involved at least one type of exercise intervention and reported changes in sleep quality assessments."},{"id":"source_24","type":"source","study":"Effects of Baduanjin exercise on cognitive frailty, oxidative stress, and chronic inflammation in older adults with cognitive frailty: a randomized controlled trial","year":2024,"doi":"10.3389/fpubh.2024.1385542","url":"https://doi.org/10.3389/fpubh.2024.1385542","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Oxidative stress and chronic inflammation play an important role in the pathogenesis process of cognitive frailty (CF). Regular Baduanjin exercise could improve cognitive frailty in older adults, but it is unclear whether the effect of Baduanjin exercise on improving CF is mediated by modulating circulating oxidative stress and inflammatory process. METHOD: A total of 102 community-dwelling older adults with CF were recruited and randomly allocated into a 24-week Baduanjin exercise training group or no specific exercise intervention control group at an equal rate. Cognitive function and physical frailty index were assessed using the Montreal Cognitive Assessment (MoCA) and the Edmonton Frail Scale (EFS), as well as the oxidative stress and inflammatory cytokines were measured at baseline and after intervention. RESULT: After 24 weeks of intervention, the increased MoCA score (2.51 ± 0.32 points, p < 0.001) and the decreased EFS scores (1.94 ± 0.20 points, p = 0.012) in the Baduanjin group were significantly higher than those in the control group. Serum antioxidant SOD levels were increased by 10.03 ± 4.73 U/mL ( p < 0."},{"id":"source_25","type":"source","study":"Combined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial","year":2026,"doi":"10.1080/15502783.2026.2646626","url":"https://doi.org/10.1080/15502783.2026.2646626","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Age-associated sarcopenia and declining physical function in older women are connected to changes in hormones, inflammation, and disrupted protein metabolism. Myokines and cytokines play central roles in muscle atrophy. While both resistance exercise (RE) and essential amino acid (EAA) supplementation are promising interventions, limited randomized trials have assessed their combined effect in healthy elderly populations. Early targeted strategies may help delay sarcopenia and promote healthier aging. METHODS: A 12-week randomized controlled trial was performed involving 96 healthy women aged ≥ 65 years without insulin resistance. Participants were randomized into four groups: control, RE, EAA, or RE + EAA. The intervention consisted of a circuit-based training program conducted three times per week, with each session lasting 60 minutes at moderate intensity. Participants in EAA and RE + EAA groups consumed 5.5g of EAA twice daily. Assessments before and after the intervention included body composition, muscle fitness, serum myokines, and inflammatory cytokines."},{"id":"source_26","type":"source","study":"Short‐Term Multicomponent Exercise Impact on Muscle Function and Structure in Hospitalized Older at Risk of Acute Sarcopenia","year":2024,"doi":"10.1002/jcsm.13602","url":"https://doi.org/10.1002/jcsm.13602","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Hospitalization exacerbates sarcopenia and physical dysfunction in older adults. Whether tailored inpatient exercise prevents acute sarcopenia is unknown. This study aimed to examine the effect of a multicomponent exercise programme on muscle and physical function in hospitalized older adults. We hypothesized that participation in a brief tailored exercise regimen (i.e., 3-5 days) would attenuate muscle function and structure changes compared with usual hospital care alone. METHODS: This randomized clinical trial with blinded outcome assessment was conducted from May 2018 to April 2021 at Hospital Universitario de Navarra, Spain. Participants were 130 patients aged 75 years and older admitted to an acute care geriatric unit. Patients were randomized to a tailored 3- to 5-day exercise programme (n = 64) or usual hospital care (control, n = 66) consisting of physical therapy if needed. The coprimary endpoints were between-group differences in changes in short physical performance battery (SPPB) score and usual gait velocity from hospital admission to discharge."},{"id":"source_27","type":"source","study":"The effects of structured aerobic exercise and mind–body exercise on cognitive function in older adults with MCI: Systematic review and meta-analysis","year":2026,"doi":"10.1097/MD.0000000000047633","url":"https://doi.org/10.1097/MD.0000000000047633","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Global aging has increased the prevalence of dementia, with mild cognitive impairment (MCI) representing a critical window for intervention. While exercise is recognized for mitigating cognitive decline, the comparative effectiveness of mind-body versus structured aerobic exercise remains unclear. METHODS: Search sources included PubMed, Web of Science, and the Cochrane Library. Randomized controlled trials (RCTs) assessing mind-body exercise (tai chi, yoga, and dance) or structured aerobic exercise (walking and cycling) in patients with MCI aged over 50 years were included. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) were used as outcome measures. Random- or fixed-effects meta-analyses were conducted using RevMan 5.4.1. Heterogeneity was assessed using the I2 statistic. Subgroup analyses examined intervention parameters. RESULTS: Twenty-six randomized controlled trials (n = 2,555) were included. Mind-body exercise significantly improved MMSE (mean difference [MD] = 1.27, 95% confidence interval [CI]: 0.99-1.55, P < .01), MoCA (MD = 1.89, 95% CI: 0.78-3.00, P = ."},{"id":"source_28","type":"source","study":"Exercise for sarcopenia in older people: A systematic review and network meta‐analysis","year":2023,"doi":"10.1002/jcsm.13225","url":"https://doi.org/10.1002/jcsm.13225","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Sarcopenia is a serious public health concern among older adults worldwide. Exercise is the most common intervention for sarcopenia. This study aimed to compare the effectiveness of different exercise types for older adults with sarcopenia. METHODS: Randomized controlled trials (RCTs) that examined the effectiveness of exercise interventions on patient-important outcomes for older adults with sarcopenia were eligible. We systematically searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials via Ovid until 3 June 2022. We used frequentist random-effects network meta-analyses to summarize the evidence and applied the Grading of Recommendations, Assessment, Development, and Evaluations framework to rate the certainty of evidence. RESULTS: Our search identified 5988 citations, of which 42 RCTs proved eligible with 3728 participants with sarcopenia (median age: 72.9 years, female: 73.3%) with a median follow-up of 12 weeks. We are interested in patient-important outcomes that include mortality, quality of life, muscle strength and physical function measures."},{"id":"source_29","type":"source","study":"Explore the Optimal Treatment Regimen Across Combinations of Variate Protein Sources and Exercise Modalities and Its Associated Factors in Older Adults: A Network Meta-Analysis and Meta-Regression of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18091409","url":"https://doi.org/10.3390/nu18091409","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Background/Objectives: Aging is closely associated with sarcopenia, which has a significant impact on muscle mass and its function. Protein supplementation (PS) brings benefits such as lean mass and strength gains during exercise training. This paper determined the optimal regimen among the composites of variate protein sources and training modalities for older individuals. Methods: We comprehensively searched the electronic databases, namely MEDLINE Complete, PEDro, the Cochrane Library, Google Scholar, EMBASE, and the China National Knowledge Infrastructure, from its inception until December 2025. We included randomized controlled trials (RCTs) that examined the effectiveness of any type of PS combined with one of three exercise types-resistance, aerobic, or multicomponent training-in untrained older adults. The main outcomes used to identify sarcopenia were assessed, including lean mass, handgrip and leg strength, and physical mobility measures. Network meta-analysis (NMA) was performed by a frequentist method using random-effects models. The estimated treatment effect was expressed as the standard mean difference (SMD) with a 95% confidence interval (CI)."},{"id":"source_30","type":"source","study":"Effects of exercise interventions on inflammatory biomarker levels in older adults with frailty and/or sarcopenia: a systematic review and meta-analysis","year":2026,"doi":"10.3389/fimmu.2026.1734359","url":"https://doi.org/10.3389/fimmu.2026.1734359","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: Excessive secretion of inflammatory biomarkers exerts adverse effects on muscle strength and function, and is associated with the development and progression of sarcopenia and frailty. For the improvement of inflammatory biomarker concentrations, given the remaining limitations of current pharmacological and nutritional therapies, exercise intervention may serve as a potential non-pharmacological intervention. The purpose of this study is to systematically evaluate the effects of exercise interventions on serum inflammatory biomarker levels in older adults with frailty and/or sarcopenia by employing a meta-analysis approach. METHODS: A systematic search was conducted in PubMed, Web of Science, Cochrane Library, EMBASE, and Scopus (from database inception to October 2025) to identify randomized controlled trials (RCTs) investigating the impact of exercise interventions on serum inflammatory biomarker levels in older adults with frailty and/or sarcopenia. Data were analyzed using RevMan 5.4 and Stata 15.1. A random-effects model was employed to calculate standardized mean differences (SMD) and 95% confidence intervals (95% CI)."},{"id":"source_31","type":"source","study":"Psychological health outcomes of traditional Chinese exercises in older adults: a meta-analysis of randomized controlled trials","year":2026,"doi":"10.7717/peerj.20773","url":"https://doi.org/10.7717/peerj.20773","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: In recent years, an increasing number of systematic reviews and meta-analyses have examined the health benefits of traditional Chinese exercises (TCEs). However, most of the reviews and meta-analyses have just focused on their effects on physical function in older adults. This study conducts a meta-analysis of existing randomized controlled trials (RCTs) to investigate the effects of TCEs on psychological health outcomes. METHODS: Five Chinese and English databases were searched from their inception to July 2, 2025. RCTs were included if they used TCE interventions to improve psychological health outcomes in older adults, such as depression, anxiety, subjective well-being, general self-efficacy, and self-esteem. Study screening and data extraction were performed independently by two reviewers at all stages. Meta-analyses were conducted using Rev Man 5.4 and Stata 17.0. Pre-determined subgroups included the type of TCEs, mode of the intervention, duration of the intervention, frequency of exercise, duration of the single exercise session, and type of control condition. RESULT: This study included 42 RCTs involving 4,317 participants."},{"id":"source_32","type":"source","study":"Effects of exercise training on depression, anxiety, and physical health-related quality of life in end-stage renal disease patients receiving maintenance hemodialysis: a systematic review and meta-analysis of randomized controlled trials","year":2026,"doi":"10.3389/fpubh.2026.1788845","url":"https://doi.org/10.3389/fpubh.2026.1788845","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Maintenance hemodialysis patients commonly have adverse emotional states of depression and anxiety, leading to a serious decline in their quality of life. Exercise therapy acts as a supplementary measure that has the potential to relieve negative emotions. However, gaps remain in the current literature. OBJECTIVE: To explore the effect of exercise intervention on depression, anxiety, and physical health-related quality of life in maintenance hemodialysis patients, and analyze the influence of population characteristics and intervention plans on the curative effect of exercise therapy. METHODS: A literature search was conducted across 12 databases from inception to November 14, 2025. Two researchers independently screened literature and extracted data based on PICOS framework. R software and Stata software were utilized for data analysis to evaluate intervention effects by calculating standardized mean differences (SMD) and 95% confidence intervals (CI). Sensitivity analysis was done by the leave-one-out method. Egger's test and trim-and-fill method were used to explore potential publication bias."},{"id":"source_33","type":"source","study":"Multicomponent Exercise Program Reduces Frailty and Inflammatory Biomarkers and Improves Physical Performance in Community-Dwelling Older Adults: A Randomized Controlled Trial","year":2020,"doi":"10.3390/ijerph17113760","url":"https://doi.org/10.3390/ijerph17113760","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"The efficacy of exercise to reverse frailty in the aging population has not been extensively investigated. This study aimed to investigate the effectiveness of a multicomponent exercise program (MCEP) on frailty, physical performance (handgrip strength, Berg Balance Scale (BBS), Timed Up and Go test (TUG), and VO 2 Max), blood biomarkers (Interleukin-6 (IL-6) and C-reactive protein (CRP)) in frail older adults. A randomized controlled trial using an allocation concealment method, included 64 older adults (77.78 ± 7.24 years), were divided into two parallel groups using block randomization: an MCEP group ( n = 32) and a control group ( n = 32). The combined center- and home-based MCEP training consisted of chair aerobic, resistance, and balance, which was carried out 3 days per week for 24 weeks. A mixed model repeated measure ANOVA demonstrated significant interaction effects of group x time for BBS, TUG and frailty scores ( p < 0.001). Additionally, the post-hoc analysis revealed that the MCEP group showed significantly improved BBS, TUG, and frailty scores ( p < 0.01), at both 12- and 24-weeks."},{"id":"source_34","type":"source","study":"Wuqinxi exercise for mind and balance: Enhancing cognition, fall prevention, and quality of life in older adults with mild cognitive impairment","year":2026,"doi":"10.1371/journal.pone.0346490","url":"https://doi.org/10.1371/journal.pone.0346490","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: The risk of falls is a global public health issue, with over 38 million disability-adjusted life years lost annually due to falls. However, older adults with mild cognitive impairment (MCI) are more likely to fall and suffer more severe injuries compared to cognitively normal older adults, which also has an impact on their quality of life. METHODS: This study was a randomized, controlled trial with two parallel groups, allocated in a 1:1 ratio using a concealed allocation mechanism and assessor blinding. 53 participants were randomly assigned to the 12-week Wuqinxi exercise group or the 12-week stretching exercise group. Overall cognitive function, risk of falls, and quality of life were assessed at baseline and at post. Independent t-tests and non-parametric tests were used to compare the outcome variables between the two groups. RESULTS: There were no significant differences in baseline demographic characteristics or assessment indicators between Wuqinxi exercise group and stretching exercise group (P > 0.05), indicating comparability between the groups."},{"id":"source_35","type":"source","study":"Effects of 12-week exercise on Meteorin-like levels, inflammation, and functional capacity in older adults: Korean national aging project randomized controlled study","year":2025,"doi":"10.1007/s41999-025-01272-2","url":"https://doi.org/10.1007/s41999-025-01272-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE: Meteorin-like protein (Metrnl) is involved in regulating inflammation, metabolism, and muscle regeneration, making it a promising therapeutic target. Building on prior research, we investigated how exercise-induced changes in Metrnl relate to inflammatory markers, physical function, and cognitive performance. This randomized controlled trial examined the effects of a 12-week exercise intervention on circulating Metrnl, a novel biomarker, in 90 community-dwelling older adults (≥ 65 years). METHODS: Participants were randomized into a walking group (WG), a combined resistance and walking group (RWG), or an active control group (CG). Intervention groups engaged in moderate-intensity exercise; walking based on age-specific step goals and resistance training twice weekly. Blood samples and assessments of physical and cognitive function were collected pre- and post-intervention. RESULTS: 79 participants successfully completed the study. After 12 weeks, serum Metrnl levels significantly increased in both RWG and WG compared to CG (WG vs. CG: p = .002; RWG vs. CG: p = .004). Metrnl changes were correlated with improvements in inflammatory markers (IL-6, p = .048; TNF-α, p = ."},{"id":"source_36","type":"source","study":"Effects of exercise interventions on cognitive function in sedentary adults: a systematic review and network meta-analysis","year":2026,"doi":"10.3389/fpubh.2026.1794345","url":"https://doi.org/10.3389/fpubh.2026.1794345","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: This study aims to systematically compare and evaluate the effects of different types of exercise interventions on cognitive function in sedentary adults through a systematic review and network meta-analysis, quantifying their relative effectiveness to provide evidence for formulating precise exercise prescriptions. METHODS: Electronic databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science, and EBSCO were systematically searched from their inception until December 30, 2025, for RCTs comparing exercise interventions with a sedentary control on cognitive outcomes in sedentary adults. Literature screening, data extraction, and risk-of-bias assessment were conducted based on predefined PICOS criteria. For global cognition and executive function, which involved multiple exercise types forming connected networks, a frequentist network meta-analysis was performed to integrate direct and indirect evidence. The surface under the cumulative ranking curve was used to rank interventions. For memory function, due to the absence of a connected network, a standard pairwise meta-analysis was conducted using a random-effects model."},{"id":"source_37","type":"source","study":"A Single Bout of Aerobic Exercise Increases Neuronal Extracellular Vesicle‐Derived Insulin Signaling Biomarkers in Adults With Cardiometabolic Risk","year":2026,"doi":"10.1002/cph4.70131","url":"https://doi.org/10.1002/cph4.70131","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"UNLABELLED: Exercise may lower Alzheimer's Disease and Related Dementia (ADRD) risk. While insulin has been proposed to benefit cognition, the effect of exercise on neuronal insulin signaling in humans is unclear. PURPOSE: We tested the hypothesis that a single bout of aerobic exercise would raise insulin signaling mediators from plasma-derived neuronal extracellular vesicles (nEVs). METHODS: Fifteen sedentary adults with obesity (12F; ~56y; ~31 kg/m 2 ) completed an evening rest and acute exercise condition (70% maximal oxygen consumption (VO 2 max)) in a randomized, counterbalanced order. Following an overnight fast, plasma was collected for analysis of nEV insulin signaling biomarkers before and after intranasal insulin spray (INI, 40 IU) as well as 60 min following a 75 g oral glucose tolerance test (OGTT). Plasma glucose and insulin were also measured at 30 and 60 min during the OGTT, and total area under the curve (tAUC) was calculated. RESULTS: Exercise tended to lower glucose tAUC 0-150min (p = 0.08, d = 0.50), independent of insulin tAUC 0-150min (p = 0.99, d = 0.00). Exercise increased pIR-Tyr1162/Tyr1163 (p = 0.05, η 2 = 0.05), pIRS-1-Ser636 (p = 0.02, η 2 = 0."},{"id":"source_38","type":"source","study":"Effects of exercise on cognitive function in older patients with Alzheimer’s disease: a meta-regression and meta-analysis","year":2026,"doi":"10.3389/fpubh.2026.1793973","url":"https://doi.org/10.3389/fpubh.2026.1793973","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: This study aimed to systematically evaluate the effects of exercise intervention on cognitive function in AD patients through meta-analysis, specifically investigating the dose-response relationships and moderating effects of various exercise prescription parameters including frequency, single-session duration, weekly total duration, total intervention duration, type, and intensity-on the magnitude of cognitive improvement. The findings are expected to provide scientific and actionable empirical evidence for designing precise and individualized exercise programs. METHODS: Relevant literatures were systematically retrieved from eight databases up to August 2025, including PubMed, Web of Science, Embase, Emcare, Scopus, Cochrane Library, Ebsco, and SPORTDiscus. All included trials were randomized controlled trials (RCTs) involving adults aged 60 years and above. These studies examined the effects of exercise intervention on cognitive function in AD patients, compared with passive control groups without exercise. A multilevel meta-analysis was used to assess the impact of exercise on cognitive function outcomes in AD patients."},{"id":"source_39","type":"source","study":"Effects of a postural balance apparatus–assisted combined exercise program on fall-related physical fitness and blood vessel elasticity among older women","year":2026,"doi":"10.1097/MD.0000000000048802","url":"https://doi.org/10.1097/MD.0000000000048802","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: In this study, we evaluated the effects of a combined exercise program incorporating a postural balance apparatus on the fall-related physical fitness and blood vessel elasticity of older women. METHODS: The participants were 36 women aged 65 years or older who did not engage in regular exercise. They were randomly divided into an exercise group (n = 18) and a control group (n = 18). The exercise group underwent a combined exercise program for 12 weeks (60 minutes a day for 5 days a week), whereas the control group engaged in no physical activity or exercise during the 12 weeks. The combined exercise program consisted of aerobic exercise (such as step-ups and the short foot exercise), resistance exercises (such as heel raises, semi-squats, and weight-bearing closed-chain exercises), and joint mobility exercises (such as step-ups with pelvic floor muscle engagement, lower body stretching, and back stretching) to be performed on a postural balance apparatus, which provided an inclined and elastic surface to facilitate ankle dorsiflexion, joint mobility, and proprioceptive stimulation."},{"id":"source_40","type":"source","study":"The effectiveness of exercise interventions on muscle strength and balance function in pre-frail older adults: a systematic review and Bayesian network meta-analysis","year":2026,"doi":"10.3389/fpubh.2025.1718120","url":"https://doi.org/10.3389/fpubh.2025.1718120","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Prefrailty represents a critical transitional phase in age-related functional decline among older adults, characterized by reduced muscle strength and impaired balance. While exercise interventions are recognized as effective in ameliorating these symptoms, the comparative efficacy of different exercise modalities remains unclear. OBJECTIVE: To evaluate the effects of different exercise interventions on muscle strength and balance function in older adults with prefrailty. DESIGN: This is a systematic review and Bayesian network meta-analysis. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) published up to March 2025. Seventeen RCTs involving older adults (age ≥ 60 years) with prefrailty were included, evaluating 10 exercise interventions (e.g., multicomponent training, elastic band exercise, progressive exercise combined with a Tai-chi snacking program, etc.). Primary outcomes included handgrip strength, the Short Physical Performance Battery (SPPB) score, and Timed Up-and-Go (TUG) test performance."},{"id":"source_41","type":"source","study":"Effects of Integrating Wearable Activity Trackers With a Home-Based Multicomponent Exercise Intervention on Fall-Related Parameters and Physical Function in Older Adults: Randomized Controlled Trial","year":2025,"doi":"10.2196/64458","url":"https://doi.org/10.2196/64458","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Older adults with a history of falling often encounter challenges in participating in group exercise programs. Recent technological advances, such as activity trackers, can potentially enhance home-based exercise programs by providing continuous physical activity monitoring and feedback. OBJECTIVE: The aim of the study is to explore whether integrating wearable activity trackers with a home-based exercise intervention is effective in reducing fear of falling and improving physical function in older adults. METHODS: This was a 12-week, parallel-group, randomized controlled trial involving 30 older adults (≥60 years) with a history of falling. Participants were randomly assigned in a 1:1 ratio to either a group combining an activity tracker with a home-based multicomponent exercise intervention, which included in-person exercise sessions, exercise videos, and objective feedback via phone calls (AT+EX group) or to a group using the activity tracker only for self-monitoring (AT-only group)."},{"id":"source_42","type":"source","study":"Effects of exercise with or without β -hydroxy- β -methylbutyrate supplementation on muscle mass, muscle strength, and physical performance in patients with sarcopenia: a systematic review and meta-analysis","year":2024,"doi":"10.3389/fnut.2024.1460133","url":"https://doi.org/10.3389/fnut.2024.1460133","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVES: This systematic review and meta-analysis aimed to assess the effects of exercise with/without β -hydroxy-β-methylbutyrate (HMB) supplementation on muscle mass, muscle strength, physical performance, and body composition in patients with sarcopenia. METHODS: A literature search for randomized controlled trials (RCTs) on the effects of exercise with or without HMB supplementation on muscle mass, muscle strength, physical performance, and body composition in patients with sarcopenia was conducted using PubMed, Web of Science, EBSCO, The Cochrane Library, EMBASE, Scopus, Science Direct, China Knowledge Resource Integrated Database (CNKI), and Wan Fang database. The search was limited to studies published up to April 2024 for each database. The outcome measures included muscle mass, muscle strength, physical performance, and body composition. The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the included literature, and RevMan 5.4 software was employed to perform a meta-analysis of the outcome indicators. RESULTS: Five RCTs involving 257 elderly patients with sarcopenia were included in this study."},{"id":"source_43","type":"source","study":"Efficacy of Exercise on Muscle Function and Physical Performance in Older Adults with Sarcopenia: An Updated Systematic Review and Meta-Analysis","year":2022,"doi":"10.3390/ijerph19138212","url":"https://doi.org/10.3390/ijerph19138212","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"This study aimed to analyze the efficacy of exercise interventions on muscle strength, muscle mass, and physical performance in older adults with sarcopenia. Randomized controlled studies assessing exercise effects on sarcopenia were searched in Web of Science, PubMed, Cochrane Library, ProQuest, EBSCOhost, Scopus, EMBASE, and VIP and CNKI up to 31 March 2022. Data were expressed as weighted/standardized mean difference (MD/SMD) with 95% confidence intervals (CI). I 2 index was employed for heterogeneity. The initial search identified 5379 studies, and 23 studies involving 1252 participants met the inclusion criteria for further analysis. Results revealed that exercise interventions can significantly improve grip strength (MD = 2.38, 95%CI = 1.33-3.43), knee extension strength (SMD = 0.50, 95%CI = 0.36-0.64), muscle mass of lower extremities (MD = 0.28, 95%CI = 0.01-0.56), walking speed (SMD = 0.88, 95%CI = 0.49-1.27), and functional mobility (MD = -1.77, 95%CI = -2.11--1.42) among older adults with sarcopenia. No significant exercise effects were found on fat-free muscle mass, appendicular muscle mass, skeletal muscle mass, and muscle mass of the upper extremities."},{"id":"source_44","type":"source","study":"Effectiveness of exercise snacks on physical function: a systematic reviews with meta-analysis of randomized controlled trials","year":2026,"doi":"10.1016/j.jnha.2026.100837","url":"https://doi.org/10.1016/j.jnha.2026.100837","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The effects of exercise snacks interventions on physical function in healthy or sub-healthy adults remain unclear. Exercise snacks intervention is defined as breaking up daily physical activity into brief, frequent bouts performed intermittently throughout the day (e.g., 1-2 min of stair climbing or bodyweight training hourly). This study aims to evaluate the effectiveness of exercise snacks interventions in improving physical function in this population. METHODS: The systematic search covered the China National Knowledge Infrastructure (CNKI), China Science and Technology Journals (VIP), Wanfang, PubMed, Embase, CINAHL, Web of Science, Cochrane Library, and Scopus databases, screening relevant randomized controlled trials published up to July 31, 2025. The risk of bias in the included studies was assessed using the Cochrane risk of bias tool, and data analysis was performed with RevMan 5.3. RESULTS: This study included 11 eligible randomized controlled trials involving 472 participants. Meta-analysis results demonstrated that exercise snacks interventions significantly increased absolute peak power output [MD = 16.53, 95%CI (2.93, 29.77), P = 0."},{"id":"source_45","type":"source","study":"Comparative effectiveness of exercise modalities and nutritional supplementation for sarcopenic obesity in older adults: a network meta-analysis based on randomized controlled trials","year":2026,"doi":"10.3389/fpubh.2026.1775783","url":"https://doi.org/10.3389/fpubh.2026.1775783","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: Sarcopenic obesity is highly prevalent among older adults and is associated with adverse clinical outcomes. However, direct comparative evidence on the relative efficacy and safety of different exercise-based rehabilitation strategies, with or without nutritional supplementation or high-protein intake, remains limited. This study aimed to compare and rank the effects of diverse rehabilitation interventions using a systematic review and network meta-analysis. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched from database inception to November 1, 2025, without language restrictions. Both Medical Subject Headings and free-text terms were used. Primary outcomes included body mass index (BMI), handgrip strength (GRIP), fat mass (FM), percentage body fat (PBF), and skeletal muscle index (SMI). A systematic review and network meta-analysis were conducted. Risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB 2) tool, and the certainty of evidence was evaluated using the CINeMA framework. The study protocol was prospectively registered in PROSPERO (CRD420251270452)."},{"id":"source_46","type":"source","study":"Effect of Baduanjin Exercise and Resistance Band Training on Sarcopenia in the Elderly: A Randomized Controlled Trial","year":2026,"doi":"10.12659/MSM.952000","url":"https://doi.org/10.12659/MSM.952000","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND Sarcopenia, the age-related loss of muscle mass and function, is a major geriatric concern. This study evaluated the impact of Baduanjin, resistance band, and mixed exercise on muscle mass and physical function in elderly sarcopenic patients. MATERIAL AND METHODS Eighty sarcopenic individuals were randomly assigned to Baduanjin, resistance band, mixed exercise, or control groups (n=20 each). Interventions were conducted 3×/week for 30 minutes over 12 weeks. Appendicular skeletal muscle mass (ASM), ASM index (ASMI), handgrip strength (HGS), gait speed (GS), Short Physical Performance Battery (SPPB) scores, and timed up-and-go test (TUGT) were measured before and after the intervention. RESULTS Before the intervention, the groups were comparable. Post-intervention within-group comparisons indicated significant improvements in ASM and ASMI in the resistance band and mixed exercise groups (P<0.05). Between-group comparisons of change scores revealed greater increases in ASM and ASMI in the resistance band group compared to the control group (P<0.05). Furthermore, post-intervention within-group comparisons shows that improvements (P<0."},{"id":"source_47","type":"source","study":"Effects of Exercise on Autonomic Cardiovascular Function in Older Adults: A Systematic Review and Meta-Analysis","year":2025,"doi":"10.1007/s40279-025-02357-5","url":"https://doi.org/10.1007/s40279-025-02357-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Physical exercise has been proposed to enhance cardiovascular autonomic function; however, current evidence in older populations remains controversial. OBJECTIVE: This systematic review and meta-analysis aimed to examine the effects of physical exercise on autonomic cardiovascular function in older adults. METHODS: A systematic literature search was conducted in PubMed, Web of Science, Scopus, and ScienceDirect on March 12, 2025, following PRISMA 2020 guidelines. Two independent reviewers applied the PICOS model to screen randomised controlled trials (RCTs) published since 2010 that investigated the effects of exercise interventions on autonomic cardiovascular function in older adults. Methodological quality was assessed using the PEDro scale. Standardised mean differences (SMD) and 95% confidence intervals (CI) were calculated through random effects models using the Empirical Bayes method. This systematic review and meta-analysis was registered in PROSPERO (CRD420250651364). RESULTS: Fifteen RCTs were included in the meta-analysis. Exercise interventions significantly increased the root mean square of the successive differences (RMSSD) (SMD 0."},{"id":"source_48","type":"source","study":"Diet and Exercise Interventions in Pediatric Cancer Survivors and Effects on Cardiometabolic Disease Risk and Inflammaging Biomarkers: A Systematic Review","year":2026,"doi":"10.1016/j.advnut.2026.100605","url":"https://doi.org/10.1016/j.advnut.2026.100605","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"The population of pediatric cancer survivors (PCSs) in the United States has been steadily increasing over the last decade. However, due to cancer-related treatment and subsequent lifestyle behaviors related to diet and physical activity, PCSs are burdened by accelerated biological aging leading to early onset of chronic diseases. The accelerated aging process may be due to \"inflammaging,\" a phenomenon associated with cardiometabolic disease risk factors, including chronic inflammation and changes in gut microbiome structure and function. This systematic review was conducted to explore the literature as it relates to the impact of diet and/or exercise interventions in survivors of a pediatric cancer on markers of inflammaging and cardiometabolic risk markers. PubMed, CINAHL, and clinicaltrials.gov were searched for relevant interventional trials. Studies were included if they contained 1) an intervention arm that included survivors of a pediatric cancer, 2) an intervention that contained a dietary and/or exercise intervention, and 3) outcomes related to cardiometabolic disease risk or inflammaging."},{"id":"source_49","type":"source","study":"Effects of an exercise program using an smartphone App with remote or in-person supervision on the functional capacity of older adults: a randomized clinical","year":2026,"doi":"10.31744/einstein_journal/2026AO1757","url":"https://doi.org/10.31744/einstein_journal/2026AO1757","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: Population aging is a significant global challenge, demanding strategies that promote healthy aging. Regular physical activity is crucial for maintaining functional capacity, quality of life, and preventing chronic diseases in older adults. However, sedentary behavior remains high, and evidence on effective, supervised smartphone-based exercise strategies for older adults is limited. OBJECTIVE: To evaluate the effects of smartphone-based exercises with in-person or remote therapeutic supervision on functional capacity. METHODS: Thirty-four older adults were randomized into two training groups with App-based exercises: a Control Group with in-person supervision and an Experimental Group with remote supervision. The exercises were performed three times a week for 8 weeks. The Experimental Group performed exercises at homes with remote supervision, and the Control Group performed exercises in the laboratory. Functional capacity was measured using the Glittre Activities of Daily Living (Glittre ADL) test, postural balance with the Mini Balance Evaluation Systems Test, and lower limb strength with the Five Times Sit-to-Stand test."},{"id":"source_50","type":"source","study":"Effectiveness of exercise intervention on muscle mass, muscle strength, and physical function among postmenopausal women with sarcopenia: a systematic review and meta-analysis","year":2026,"doi":"10.3389/fpubh.2026.1758325","url":"https://doi.org/10.3389/fpubh.2026.1758325","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Sarcopenia is highly prevalent among postmenopausal women due to hormonal changes and aging, and is associated with adverse health outcomes. Exercise has been proposed as a key strategy to mitigate sarcopenia; however, its effectiveness in this population remains inconclusive. OBJECTIVE: To systematically evaluate the effects of different exercise modalities on muscle mass, muscle strength, and physical function in postmenopausal women with sarcopenia. METHODS: A systematic search was conducted across six electronic databases from inception to April 1, 2025. Randomized controlled trials evaluating exercise interventions in postmenopausal women with sarcopenia were included. Primary outcomes were muscle mass, muscle strength, and physical performance. Meta-analyses were performed using RevMan and Stata. RESULTS: A total of 17 RCTs involving 744 postmenopausal women with sarcopenia were included in this systematic review. The pooled analysis revealed that exercise interventions significantly improved skeletal muscle mass index. Additionally, significant improvements were found in muscle strength, including grip strength and knee extension strength."},{"id":"source_51","type":"source","study":"A systematic review and meta-analysis of the effects of resistance exercise on cognitive function in older adults","year":2025,"doi":"10.3389/fpsyt.2025.1708244","url":"https://doi.org/10.3389/fpsyt.2025.1708244","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: Cognitive decline has become a major concern with global population ageing, profoundly affecting quality of life and social participation in older adults. Resistance exercise has recently gained attention as a promising strategy to promote neuroplasticity and mitigate cognitive deterioration; however, evidence from randomized controlled trials (RCTs) remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of resistance exercise on cognitive function in older adults and to examine whether improvements vary by age and whether exercise parameters-such as type, duration, session length, and weekly frequency-show dose-response relationships. METHODS: PubMed, Web of Science, Cochrane Library, Embase, and Science Direct were systematically searched from database inception to September 2024 for RCTs investigating the effects of resistance training on cognitive function in older adults (≥60 years). Study quality was assessed using the Cochrane Risk of Bias 2 (ROB2) tool, and meta-analyses were conducted using RevMan 5.4 and Stata 17. RESULTS: 17 RCTs (n =739) met the inclusion criteria."},{"id":"source_52","type":"source","study":"Cognitive and physical exercise to improve outcomes after surgery (COPE-iOS) study: protocol for a randomised, controlled trial in the USA examining the efficacy of a combined cognitive and physical exercise programme performed before and after major surgery in improving cognitive and functional out","year":2026,"doi":"10.1136/bmjopen-2025-110435","url":"https://doi.org/10.1136/bmjopen-2025-110435","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: Surgery and its resulting hospitalisation are associated with subsequent cognitive and functional decline. Interventions to reduce this decline have exhibited limited success. Prehabilitation is the process of enhancing capacity and reserve before an acute stressor to improve tolerance of the acute physiologic insult. Older adults requiring major surgery are an ideal population for prehabilitation. Prehabilitation exercise studies have mostly focused on physical training to improve physical outcomes after specific surgery types, and data on cognitive outcomes and in broader surgical populations are needed. Computerised cognitive training (CCT) has been shown to enhance memory, processing speed, attention and multitasking. Combining CCT with a physical exercise may be most effective in reducing cognitive and functional decline in older patients undergoing major surgery, but has yet to be evaluated."},{"id":"source_53","type":"source","study":"The effects of vitamin K 2 on recovery from muscle damaging resistance exercise in young and older adults – The TAKEOVER randomised controlled trial","year":2026,"doi":"10.1249/MSS.0000000000003901","url":"https://doi.org/10.1249/MSS.0000000000003901","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"PURPOSE: Vitamin K2 supplementation has emerged as a strategy to enhance recovery and modulate postexercise physiological responses. This study aimed to assess the effects of vitamin K2 on recovery from muscle-damaging exercise in young and older adults. METHODS: Healthy young (18-40 yr) and older (65+ yr) adults were randomly assigned to either vitamin K2 (menaquinone-7, MK-7, 240 μg/d) or placebo (cellulose) for 12 wk in this double-blind randomized controlled trial. Before and after supplementation, knee extensor maximal torque, functional ability, muscle soreness, and systemic blood markers of muscle damage and inflammation were measured before (0 h) and 3, 24, 48, and 72-h postexercise. Data were analyzed using regression and mixed models. RESULTS: Seventy-one participants (35 young and 36 older) completed the study, with 12 wk of vitamin K2 supplementation increasing circulating MK-7 levels (P-value <0.001). There were no supplement × time effects for any variables. Significant supplement × time × older age interaction effects were noted for electromechanical delay (EMD) (P-value = 0.03), electromyography root mean square (RMS) (P-value = 0."},{"id":"source_54","type":"source","study":"LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial","year":2026,"doi":"10.1136/bmjopen-2026-116911","url":"https://doi.org/10.1136/bmjopen-2026-116911","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"INTRODUCTION: Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy."},{"id":"source_55","type":"source","study":"Effects of high-intensity interval training on glycemic control and cardiometabolic risk factors in adults with prediabetes: a systematic review and meta-analysis","year":2026,"doi":"10.3389/fendo.2026.1837386","url":"https://doi.org/10.3389/fendo.2026.1837386","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: To systematically review and meta-analyze intervention studies evaluating the effects of high-intensity interval training (HIIT) in adults with prediabetes, with a focus on glycemic control and cardiometabolic risk-related outcomes. METHODS: PubMed, Embase, Web of Science, EBSCO, and the Cochrane Library were searched from inception to January 2026. Eligible studies included adults with prediabetes who participated in structured HIIT, with either a non-exercise control or an exercise comparator. Primary outcomes were glycemic measures, and secondary outcomes were cardiometabolic risk-related indicators. Change-from-baseline values were used preferentially for pooling effect sizes. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, heterogeneity using Cochran's Q and I², and certainty of evidence using GRADE. This review was registered in PROSPERO (CRD42024605154). RESULTS: Thirteen intervention studies were included. Because of the limited number of eligible studies, no quantitative synthesis was performed for comparisons with non-exercise controls or across different HIIT protocols."},{"id":"source_56","type":"source","study":"Baduanjin exercise improves functional capacity and cardiovascular function in older adults with cardiovascular diseases: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fcvm.2025.1419095","url":"https://doi.org/10.3389/fcvm.2025.1419095","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Based on clinical observations and expert recommendations, Baduanjin exercise has demonstrated a positive impact on maintaining and enhancing cardiovascular function. Despite clinical observations of Baduanjin's cardiovascular benefits, systematic evidence for older adults remains limited. Moreover, the effects of Baduanjin exercise on functional capacity in older adults with cardiovascular diseases have not been adequately investigated. Therefore, we conducted a systematic review and meta-analysis to evaluate the overall efficacy and effectiveness of Baduanjin exercise on functional capacity and cardiovascular function in older adults with cardiovascular diseases. METHODS: We conducted a systematic review and meta-analysis, searching related trials through March 7, 2025, across six databases: PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and China Science Journal Database (VIP). Methodological quality was assessed using the Cochrane Risk of Bias Tool, and a meta-analysis of comparative effects was performed using Review Manager v.5.3 software."},{"id":"source_57","type":"source","study":"Effectiveness of exercise based on wearable electronic devices on lower limb strength and balance in older adults: a systematic review and meta-analysis","year":2026,"doi":"10.3389/fpubh.2026.1778082","url":"https://doi.org/10.3389/fpubh.2026.1778082","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effectiveness of wearable electronic device-based exercise interventions on lower limb strength and balance in older adults. METHODS: A systematic search was conducted following PRISMA guidelines to evaluate the impact of exercise based on wearable electronic devices on health behaviors (such as muscle strength, balance, endurance, mental health, and cognitive function) in older adults. This meta-analysis included 13 two-arm, between-group studies and 4 single-arm, within-group studies, involving a total of 611 participants. The inclusion of single-arm studies in the meta-analysis was based on the limited availability of two-arm studies and to maximize the available evidence for understanding the broader effects of the intervention. RESULTS: The results show that in the meta-analysis of two-arm controlled studies, exercise based on wearable electronic devices significantly improved lower limb strength (SMD = -0.60; 95% CI [-1.15, -0.05]; p < 0.001; I 2 = 81%) and balance (SMD = -0.43; 95% CI [-0.81, -0.06]; I 2 = 17%) in older adults."},{"id":"source_58","type":"source","study":"Reducing frailty in frail people with multiple sclerosis: Feasibility of a 6-week multimodal exercise training program","year":2026,"doi":"10.1371/journal.pone.0347063","url":"https://doi.org/10.1371/journal.pone.0347063","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Frailty is increasingly recognized as a prevalent and debilitating condition in people with multiple sclerosis (MS) and is linked to poorer health outcomes. However, targeted interventions remain limited. The objective of this study was to examine the feasibility of a multimodal exercise training (MET) program to reduce frailty in frail people with MS. MATERIALS AND METHODS: Sixteen frail people with MS (age = 55.0 ± 7.7 years, 81.3% female, Fried frailty score ≥3) participated in this pilot randomized controlled trial. Participants were randomly assigned to a 6-week MET program consisting of virtual reality treadmill training + resistance training (n = 8) or to a waitlist control group (n = 8). Feasibility outcomes included recruitment, retention, and adherence rates as well as safety and user engagement throughout the study (Study Participant Feedback Questionnaire-SPFQ). Exploratory outcomes were collected at baseline and 6 weeks and included the Evaluative Frailty Index for Physical Activity (EFIP), the 54-item MS Quality of Life questionnaire (MSQoL-54), the Modified Fatigue Impact Scale (MFIS), and the Physiological Profile Assessment (PPA)."},{"id":"source_59","type":"source","study":"Effect of leucine-enriched essential amino acid supplementation combined with different exercise regimen on appendicular skeletal muscle mass and muscle performance in older adults: an open label randomized controlled trial","year":2026,"doi":"10.1093/jbmrpl/ziag052","url":"https://doi.org/10.1093/jbmrpl/ziag052","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Sarcopenia in older adults increases fall risk and frailty. Improving muscle mass and function enhances balance and supports basic activities of daily living. Leucine-enriched essential amino acid supplementation combined with resistance training has been shown to enhance muscle performance. The present study evaluated muscle performance outcomes after 6 mo of these treatments. In an open-label randomized controlled trial, 66 participants were randomized equally to control and intervention groups ( n = 33 each). Both groups consumed daily leucine-enriched essential amino acid supplements after exercise. The intervention group performed resistance training, and the control group followed regular walking and strengthening exercises. Primary outcomes were appendicular skeletal muscle mass index (ASMI), gait speed, and hand grip strength. Safety was assessed by adverse event reporting and laboratory tests. The results of this study show no significant improvement in ASMI in either group after 6 mo. Both groups demonstrated significant gait speed improvements, with no between-group difference. Hand grip strength improved only in the non-dominant hand of the control group."},{"id":"source_60","type":"source","study":"Effects of multimodal exercise programme combined with high-protein diet on glycaemic control in older adults with type 2 diabetes mellitus: study protocol for a randomised controlled trial","year":2026,"doi":"10.1136/bmjopen-2026-118313","url":"https://doi.org/10.1136/bmjopen-2026-118313","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: Effective management of type 2 diabetes mellitus (T2DM) in older adults requires interventions that address both metabolic control and functional capacity. Exercise improves insulin sensitivity, glucose uptake and cardiometabolic health, while high-protein diets support muscle mass preservation, satiety and glycaemic regulation. Evidence suggests that integrating structured exercise with a high-protein diet may provide additive benefits; however, research evaluating this combined approach in older adults with T2DM, particularly in low-resource settings, is limited. This study aims to determine whether a 12-week multimodal exercise programme combined with a high-protein diet improves glycaemic control and broader health outcomes compared with exercise alone. METHODS AND ANALYSIS: In this randomised controlled trial (RCT), 140 adults aged ≥60 years with T2DM will be allocated 1:1 to an experimental group (multimodal exercise with high-protein diet, n=70) or a control group (multimodal exercise alone, n=70). All participants will engage in three supervised exercise sessions per week for 12 weeks."},{"id":"source_61","type":"source","study":"Gut Microbiota Changes Following Aerobic Exercise in Malnourished Octogenarians: An Assessor-Blinded Intervention Study Stratified by Nutritional Status","year":2026,"doi":"10.3390/nu18101627","url":"https://doi.org/10.3390/nu18101627","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND/OBJECTIVES: Global population aging is associated with a rising prevalence of malnutrition among adults aged ≥80 years. Gut dysbiosis is linked to immune decline and impaired nutrient absorption, and aerobic exercise may enhance microbial diversity. This study investigated gut microbiota changes after a 12-week aerobic exercise intervention in octogenarians stratified by nutritional status. METHODS: A total of 129 nursing home residents (≥80 years) were classified via the Mini Nutritional Assessment Short-Form (MNA-SF) into a healthy group (HG, MNA-SF ≥ 11) and a malnourished group (MG, MNA-SF < 11). Both groups underwent a 12-week brisk walking intervention (three sessions/week, 1 h/session, 40-60% heart rate reserve). Fecal samples were collected at baseline and post-intervention and were analyzed via shotgun metagenomic sequencing. RESULTS: A total of 36 participants completed the intervention (HG = 17, MG = 19). Within-group baseline-to-post-intervention analysis showed no significant changes in alpha or beta diversity in the MG. However, post-intervention between-group comparison revealed higher microbial richness and diversity in the MG vs."},{"id":"source_62","type":"source","study":"The Effects of Astaxanthin Supplementation on Exercise Recovery Biomarkers and Exercise Performance: A Systematic Review and Meta-Analysis","year":2026,"doi":"10.3390/nu18101570","url":"https://doi.org/10.3390/nu18101570","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Background : Astaxanthin is a lipid-soluble carotenoid with antioxidant and anti-inflammatory properties, but its effects on exercise performance and post-exercise recovery remain uncertain. This systematic review and meta-analysis aimed to evaluate the effects of astaxanthin supplementation on exercise performance and recovery-related biomarkers in healthy participants and athletes. Methods : This review followed PRISMA 2020 guidelines. PubMed, Web of Science, Embase, EBSCO, the Cochrane Library, and CNKI were searched from inception to January 2026. Randomized controlled trials comparing oral astaxanthin supplementation with placebo or control were included. Performance outcomes included VO 2 max, time-trial or endurance-related performance, and maximal workload or power output. Recovery-related outcomes included creatine kinase, lactate dehydrogenase, malondialdehyde, interleukin-6, and related biomarkers. Standardized mean differences with 95% confidence intervals were pooled. Results : Twenty-four RCTs were included. Astaxanthin significantly reduced creatine kinase levels (SMD = -0.45, 95% CI: -0.83 to -0.07). Lactate dehydrogenase also favored astaxanthin (SMD = -0."},{"id":"source_63","type":"source","study":"Effects of a 24-week resistance exercise program on Alzheimer’s disease brain signatures in cognitively unimpaired older adults: a secondary analysis of the AGUEDA randomized controlled trial","year":2026,"doi":"10.1093/ageing/afag086","url":"https://doi.org/10.1093/ageing/afag086","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Brain imaging markers may help detect early cognitive decline and Alzheimer's disease (AD). Although exercise-related effects on AD-specific brain signatures remain unclear. OBJECTIVE: To examine the effects of a 24-week resistance exercise (RE) program on AD brain signatures in cognitively unimpaired older adults, to explore potential moderators and to assess associations with cognition, including mediation effects. METHODS: This secondary analysis of a single-site, two-arm, single-blinded randomized controlled trial included 90 participants (72 ± 4 years; 58% female) randomly assigned by a blind external researcher to an RE group (3 sessions/week, 60 min/session, n = 46) or a wait-list control group (CG, n = 44). T1- and diffusion-weighted MRI were acquired at baseline and post-intervention. Primary outcomes were thickness/volume and grey matter mean diffusivity (GMMD) signatures, derived from cortical and hippocampal regions. Moderators included age, sex, education, multimorbidity, apolipoprotein E ϵ4 status, amyloid beta (Aβ) status and baseline AD brain signatures. Secondary outcomes included cognitive function."},{"id":"source_64","type":"source","study":"Effect of multicomponent exercise intervention on older adults with mild cognitive impairment based on HAPA-TPB theory (MIND-STEP): trial design and baseline data for a randomized controlled trial","year":2026,"doi":"10.1186/s13063-026-09640-4","url":"https://doi.org/10.1186/s13063-026-09640-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Physical exercise has emerged as a promising non-pharmacological approach for improving cognitive and physical function in older adults with mild cognitive impairment (MCI). However, most existing interventions in nursing homes lack a strong theoretical foundation, standardized delivery, and evidence-based practice. This study aims to develop and evaluate a multicomponent exercise program grounded in the Health Action Process Approach-Theory of Planned Behavior theory (HAPA-TPB) to improve adherence and cognitive outcomes in older adults with MCI living in nursing homes. METHODS: This is a randomized, single-blind, parallel-group controlled trial conducted in nursing homes in Huzhou, China. A total of 156 older adults with MCI were randomly assigned to either a 12-week, group-based multicomponent exercise intervention or a control group receiving usual care. The intervention, theoretically grounded in an integrated HAPA-TPB framework, integrates aerobic, resistance, and mind-body training with structured behavioral change strategies designed to enhance motivation, adherence, and sustained engagement, including peer interaction."},{"id":"source_65","type":"source","study":"The impact of exercise interventions before, during, and following neoadjuvant therapies for locally advanced rectal cancer: a critical review","year":2026,"doi":"10.2340/1651-226X.2026.44930","url":"https://doi.org/10.2340/1651-226X.2026.44930","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND AND PURPOSE: Neoadjuvant chemoradiotherapy (NACRT) and radiotherapy (NART) are standard treatments for locally advanced rectal cancer (LARC). However, their associated toxicities negatively affect patients' quality of life (QoL), prompting growing interest in exercise as a supportive intervention. This critical narrative review synthesised evidence on exercise interventions delivered before, during, or after NACRT/NART, with a focus on feasibility, safety, functional, psychosocial, and emerging oncological outcomes. MATERIALS AND METHODS: A systematic literature search was conducted across MEDLINE, CINAHL Ultimate, and SPORTDiscus (2010-2025). Prospective studies evaluating exercise-based interventions in patients with LARC receiving NACRT or NART were included. Studies were selected using the Participants, Exposure, and Outcome framework, and methodological quality was appraised using Critical Appraisal Skills Programme checklists. Data were synthesised narratively in accordance with PRISMA reporting standards. RESULTS: Sixteen studies met the inclusion criteria. Interventions varied in type, intensity, supervision, and timing."},{"id":"source_66","type":"source","study":"Study protocol for a multiarm, randomized controlled trial to determine the effectiveness of community-based frailty rehabilitation to improve physical function in older adults: The OPTIMAL Fitness Trial","year":2026,"doi":"10.1371/journal.pone.0343338","url":"https://doi.org/10.1371/journal.pone.0343338","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Frailty in older adults is on the rise with the rapid aging population. Frailty is dynamic and proven to be reversible or treatable. Evidence regarding the clinical effectiveness of community-based frailty interventions is limited. Frailty rehabilitation has the potential to be an accessible community-based intervention that may enable independence. We will examine a model of frailty rehabilitation and consider key components for improving physical function, frailty, sarcopenia, and cost-effectiveness. METHODS: A multiarm, parallel-group, partially blinded, randomized controlled trial will compare the clinical and cost-effectiveness of OPTimizing Independence, Mobility, and Active Life (OPTIMAL) Fitness multimodal (group exercise, nutritional coaching/supplementation, medication optimization) versus OPTIMAL Fitness exercise-only and control. Participants in the OPTIMAL Fitness multimodal and exercise-only groups will attend exercise classes twice weekly for 4 months and be provided with a tailored one-hour home exercise program. We will recruit community-dwelling older adults living with frailty aged ≥65 years."},{"id":"source_67","type":"source","study":"Effect of multicomponent exercise intervention on multidimensional frailty in older adults with mild cognitive impairment: a secondary analysis of the MIND-STEP randomised clinical trial.","year":2026,"doi":"10.1093/ageing/afag111","url":"https://doi.org/10.1093/ageing/afag111","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Frailty is common among older adults with mild cognitive impairment (MCI) and encompasses physical, cognitive, psychological and social domains, yet randomised evidence on theory-informed multicomponent exercise interventions targeting multidimensional frailty remains limited. This secondary analysis of the MIND-STEP RCT evaluated intervention effects across frailty domains. METHODS: MIND-STEP was a single-blind, parallel-group RCT conducted in nursing homes in China. Participants were randomised (1:1) to a 12-week group-based multicomponent exercise programme incorporating peer interaction and self-efficacy strategies, or to usual care. Eligible participants were adults with MCI aged ≥60 years who did not engage in regular physical exercise. Frailty domains, including physical, cognitive, psychological, social and multidimensional, were assessed at baseline, 6, 12 and 24 weeks. Generalised estimating equations within a difference-in-differences framework were used to estimate between-group risk differences. FINDINGS: Among 156 randomised participants [mean age, 69.19 years; 108 women (69.23%)], baseline prevalence was 19.23% for physical/cognitive frailty, 27."},{"id":"source_68","type":"source","study":"Effectiveness of physical exercise on foot pain and function in adults with rheumatoid arthritis: systematic review and meta-analysis","year":2026,"doi":"10.1007/s10067-026-08044-8","url":"https://doi.org/10.1007/s10067-026-08044-8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Foot involvement is highly prevalent in rheumatoid arthritis (RA), affecting over 90% of patients during the disease course. However, the specific impact of structured exercise on foot pain and functional limitations remains insufficiently understood. This systematic review and meta-analysis aimed to evaluate the effectiveness of supervised exercise programs on foot-specific outcomes in adults with RA. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines, searching five databases for randomized and controlled quasi-experimental trials evaluating supervised exercise interventions in adults with RA and foot involvement. Primary outcomes included foot pain and physical function measures. Data were pooled using random-effects models, and risk of bias was assessed using Cochrane tools. Analysis was performed with RevMan 5.4 and STATA 17. RESULTS: Thirteen studies (n = 548) were included; ten entered the meta-analysis. Exercise significantly reduced foot pain (SMD - 0.68, 95% CI - 0.89 to - 0.46; p < 0.001) and improved function (Health Assessment Questionnaire SMD - 0.73, 95% CI - 0.96 to - 0.49; 6MWT MD + 47.6 m, 95% CI 31.4 to 63."},{"id":"source_69","type":"source","study":"Impact of an exercise and nutrition program on caregiver time with residents in institutional care—A secondary analysis","year":2026,"doi":"10.1002/alz.71198","url":"https://doi.org/10.1002/alz.71198","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"INTRODUCTION: Residents in long-term institutional care (LTIC) settings are at risk of malnutrition, sarcopenia, and frailty. In the Older Persons Exercise and Nutrition (OPEN) randomized study, the impact of exercise and nutrition was analyzed. This secondary analysis focused on caregiver time (CGT). METHODS: The 3-month intervention included repeated sit-to-stand exercises and two protein-enriched supplements daily. CGT was assessed in both dementia and somatic units using the Resource Utilization in Dementia instrument. Non-linear methods were applied due to skewed data. RESULTS: The sample consisted of 102 persons (intervention group [IG] n = 52, control group [CG] n = 50). CGT in the IG was significantly lower at follow-up, adjusted for baseline CGT, in the dementia units, that is, 55 min/day and resident, compared to 83 min/day in the CG (odds ratio 0.668 [0.473-0.945]; p = 0.022). DISCUSSION: A structured exercise and nutrition program was associated with reduced CGT in the dementia, but not the somatic, LTIC units. CLINICAL TRIAL REGISTRATION: This study has been registered with the number protocol of ClinicalTrials.gov Identifier: NCT02702037."},{"id":"source_70","type":"source","study":"Modality-specific effects of structured exercise on immunometabolic biomarkers in postmenopausal obesity: a Bayesian network meta-analysis","year":2026,"doi":"10.3389/fimmu.2026.1763558","url":"https://doi.org/10.3389/fimmu.2026.1763558","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: The present Bayesian network meta-analysis (NMA) aims to evaluate and compare the efficacy of aerobic training (AT), resistance training (RT), high-intensity interval training (HIIT), and combined training (CT) on biomarkers of chronic low-grade systemic inflammation (CLGSI) in postmenopausal women with overweight or obesity. METHODS: Five databases were systematically searched from inception to November 2025 (PROSPERO: CRD420251237915) for randomized controlled trials (RCTs). Inclusion required strict clinical verification of postmenopausal status and adiposity. Standardized mean differences (SMDs) with 95% credible intervals (CrIs) quantified comparative efficacy. Surface Under the Cumulative Ranking curve (SUCRA) established probabilistic hierarchical rankings, and the GRADE framework evaluated the certainty of evidence. RESULTS: Synthesis of 39 RCTs ( N = 2,714; mean age: 58.8 ± 9.2 years) indicated biomarker-specific adaptations. RT produced the largest reduction in systemic C-reactive protein (CRP) (SMD = -0.97, 95% CrI [-1.52, -0.42]), followed by AT (SMD = -0.57, 95% CrI [-1.16, -0.02]). CT downregulated circulating interleukin-6 (IL-6) (SMD = -1.58, 95% CrI [-2."},{"id":"source_71","type":"source","study":"Effects of a smartphone-monitored physical exercise management program on the recovery of patients after endovascular repair of abdominal aortic aneurysm: a randomized controlled trial","year":2026,"doi":"10.1186/s13063-025-08948-x","url":"https://doi.org/10.1186/s13063-025-08948-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Physical exercise is known to enhance vascular function by regulating PPARs, ERs, and RXR signaling pathways. It improves cardiopulmonary capacity through optimized lipid metabolism, immune regulation, and blood pressure reduction. Additionally, exercise reduces postoperative complications by maintaining energy expenditure and skeletal muscle function, which may ultimately improve patients' quality of life (QoL). However, the safety and efficacy of exercise therapy post-endovascular aortic aneurysm repair (EVAR) remain uncertain. Due to the potential impact of exercise training on abdominal pressure, supervised exercise by medical professionals is crucial for ensuring patient safety. Although exercise offers notable benefits, patient adherence tends to be low. Therefore, leveraging smartphones as pervasive monitoring tools may provide timely feedback on patients' exercise status and influence their behavior. This trial aims to assess whether a smartphone-monitored physical exercise management program, including physical exercise interventions under medical supervision for 3 months, affects the short-term QoL of individuals post-EVAR."},{"id":"source_72","type":"source","study":"Effects of exercise on body composition, physical function, and metabolic health in older adults with sarcopenic obesity: A systematic review and meta-analysis.","year":2026,"doi":"10.1016/j.maturitas.2026.108934","url":"https://doi.org/10.1016/j.maturitas.2026.108934","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Exercise interventions benefit body composition, physical function, and metabolic health in older adults with sarcopenic obesity (SO), but the comparative effects of different types of exercise remain unclear. This study conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate overall and type-specific effects. Six databases were systematically searched up to December 2025. Twenty RCTs with a total of 917 participants (mean age 64.1-81.4 years) were included. Overall, exercise significantly reduced body mass index (BMI; MD = -0.51; 95%CI: -0.76 to -0.25), body fat mass (BFM; MD = -1.74; 95%CI: -2.67 to -0.81), body fat percentage (PBF; MD = -2.64; 95%CI: -3.27 to -2.00), and low-density lipoprotein cholesterol (LDL-C; MD = -7.17; 95%CI: -13.62 to -0.71), and increased appendicular skeletal muscle (ASM; MD = 0.34; 95%CI: 0.13 to 0.55), skeletal muscle index (SMI; MD = 0.21; 95%CI: 0.10 to 0.32), handgrip strength (HG; SMD = 0.97; 95%CI: 0.47 to 1.47), gait speed (GS; MD = 0.14; 95%CI: 0.07 to 0.21), knee extension strength (KES; SMD = 0.36; 95%CI: 0.06 to 0.65), and insulin-like growth factor 1 (IGF-1; SMD = 0.65; 95%CI: 0.30 to 1.00)."},{"id":"source_73","type":"source","study":"Preferences of frail elderly patients with cardiovascular disease for web-based exercise telerehabilitation interventions in China: protocol for a discrete choice experiment study","year":2026,"doi":"10.1136/bmjopen-2025-111370","url":"https://doi.org/10.1136/bmjopen-2025-111370","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"INTRODUCTION: Individuals with cardiovascular disease are prone to frailty, while frailty accelerates disease progression and worsens outcomes. Exercise interventions are essential non-pharmacological treatments for frail elderly patients with cardiovascular disease; however adherence remains low and strategies are inconsistent. Telerehabilitation improves accessibility, allows continuous monitoring with timely clinical responses and helps overcome mobility and geographical barriers for frail older adults. Guided by the patient-centred approach, exercise telerehabilitation should consider both clinical effectiveness and patient preferences to enhance acceptance and adherence. However, patient preferences for web-based exercise telerehabilitation remain poorly understood. METHODS AND ANALYSIS: This study is designed as a discrete choice experiment to elicit and quantify preferences for key features of web-based exercise telerehabilitation among frail older adults with cardiovascular disease. Candidate attributes and levels were developed through a systematic literature review, patient focus groups and expert consultation."},{"id":"source_74","type":"source","study":"Fun Exercise for Older Adults (FEXO): study protocol for a randomised controlled trial on intrinsic capacity, adherence and motivation","year":2026,"doi":"10.1136/bmjopen-2025-115440","url":"https://doi.org/10.1136/bmjopen-2025-115440","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"INTRODUCTION: Ageing is associated with declines in physical and cognitive function that increase the risk of disability and dependence. Intrinsic capacity (IC), proposed by the WHO, provides a multidimensional framework to assess health in older adults. This study aims to evaluate whether a multicomponent recreational exercise programme (Fun Exercise for Older Adults (FEXO)) improves IC, motivation and adherence compared with a conventional programme (OTAGO). METHODS AND ANALYSIS: A randomised controlled trial with two groups (2:1 ratio) will be conducted among 120 community-dwelling older adults (≥60 years). Participants will be randomly assigned to FEXO (intervention) or OTAGO (control). Both programmes will consist of 3 weekly sessions for 14 weeks. PRIMARY OUTCOMES: IC, assessed through validated measures (Short Physical Performance Battery, Mini Nutritional Assessment, Mini-Mental State Examination, Cornell Scale for Depression in Dementia and sensory evaluation), motivation (BREQ-3) and adherence rate. Secondary outcomes include body composition, cardiovascular parameters, frailty, cognition and resilience (PRIFOR)."},{"id":"source_75","type":"source","study":"Physical exercise programmes to improve insomnia or poor sleep quality in non-hospitalised elderly people: a systematic review and meta-analysis","year":2026,"doi":"10.7717/peerj.20764","url":"https://doi.org/10.7717/peerj.20764","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Insomnia, or poor quality of sleep, among older people increasingly affects both physical and psychological health. This study aimed to evaluate the efficacy of physical exercise programs for improving sleep quality in non-hospitalized older adults, via objective methods such as actigraphy and polysomnography. METHODS: A systematic review and meta-analysis was conducted between January 1, 2025 and March 31, 2025 according to the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide. It has been registered in Prospero with the number CRD420251009838. The following databases were consulted: PubMed, Web of Science, CINAHL Complete and Scopus. The studies included groups of participants with a mean age above 60 years, who presented with sleep problems, insomnia or an interest in improving sleep quality. To assess the quality of the studies, the Rob-2 tool for randomized studies and crossover studies and the critical appraisal of the Joanna Briggs Institute were used. RESULTS: Seven experimental or quasi-experimental studies with intervention groups and/or controls published in the last decade were analyzed."},{"id":"source_76","type":"source","study":"Comparative efficacy of combined exercise and nutritional interventions for sarcopenia: A systematic review and network meta-analysis incorporating remote delivery models.","year":2026,"doi":"10.1016/j.archger.2026.106239","url":"https://doi.org/10.1016/j.archger.2026.106239","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: To identify the most effective interventions to delay the progression of sarcopenia and potentially improve muscle strength and mass, with the ultimate goal of reversing sarcopenia, by comparing all pharmacological and non-pharmacological interventions. DESIGN: Systematic review and network meta-analysis. FINDINGS: This analysis identified 115 randomized controlled trials (RCTs) with 10,967 participants which an average age of 74.85 years, together evaluating 27 different interventions. For the primary outcome, endurance training followed by resistance training yielded the highest effect on muscle strength (SMD 2.59, 95% CI 1.50 to 3.69), while general remote training was most effective for lean mass (SMD 1.35, 95% CI 0.41 to 2.29) and physical performance (SMD 2.39, 95% CI 1.26 to 3.53). The combination of nutrition with aerobic and resistance training significantly improved muscle strength (SMD 1.25, 95% CI 0.64 to 1.87) and physical performance (SMD 1.73, 95% CI 1.09 to 2.37). Resistance training significantly improved multiple secondary outcomes: body fat mass (SMD -0.57, 95% CI -0.75 to -0.40), blood inflammatory markers (SMD -1.69, 95% CI -1.95 to -1."},{"id":"source_77","type":"source","study":"The Role of Muscle Mass Gain Following Protein Supplementation Plus Exercise Therapy in Older Adults with Sarcopenia and Frailty Risks: A Systematic Review and Meta-Regression Analysis of Randomized Trials","year":2019,"doi":"10.3390/nu11081713","url":"https://doi.org/10.3390/nu11081713","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Aging and frailty are associated with a high risk of lean mass (LM) loss, which leads to physical disability and can be effectively alleviated by protein supplementation (PS) and muscle strengthening exercise (MSE). In this study, the associations between LM gain and PS + MSE efficacy (measured using physical outcomes) in elderly patients with a high risk of sarcopenia or frailty were identified. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) reporting the efficacy of PS + MSE in elderly patients with sarcopenia or frailty. The included RCTs were analyzed using meta-analysis and risk of bias assessment. We finally included 19 RCTs in this meta-analysis with a median (range/total) Physiotherapy Evidence Database score of 7/10 (5-9/10). The PS + MSE group exhibited significant improvements in the whole-body LM (standard mean difference (SMD) = 0.66; p < 0.00001), appendicular LM (SMD = 0.35; p < 0.00001), leg strength (SMD = 0.65; p < 0.00001), and walking capability (SMD = 0.33; p = 0.0006)."},{"id":"source_78","type":"source","study":"Cardiovascular Effects and Benefits of Exercise","year":2018,"doi":"10.3389/fcvm.2018.00135","url":"https://doi.org/10.3389/fcvm.2018.00135","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"It is widely accepted that regular physical activity is beneficial for cardiovascular health. Frequent exercise is robustly associated with a decrease in cardiovascular mortality as well as the risk of developing cardiovascular disease. Physically active individuals have lower blood pressure, higher insulin sensitivity, and a more favorable plasma lipoprotein profile. Animal models of exercise show that repeated physical activity suppresses atherogenesis and increases the availability of vasodilatory mediators such as nitric oxide. Exercise has also been found to have beneficial effects on the heart. Acutely, exercise increases cardiac output and blood pressure, but individuals adapted to exercise show lower resting heart rate and cardiac hypertrophy. Both cardiac and vascular changes have been linked to a variety of changes in tissue metabolism and signaling, although our understanding of the contribution of the underlying mechanisms remains incomplete. Even though moderate levels of exercise have been found to be consistently associated with a reduction in cardiovascular disease risk, there is evidence to suggest that continuously high levels of exercise (e.g."}],"edges":[{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_1","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_2","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_3","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_4","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_5","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_6","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_7","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_8","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_9","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_10","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_11","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_12","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_13","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_14","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_15","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_16","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_17","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_18","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_19","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_20","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_21","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_22","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_23","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_24","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_25","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_26","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_27","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_28","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_29","type":"contains_claim"},{"from":"84684243-0efc-4410-8f68-b4c95ab112c0","to":"claim_30","type":"contains_claim"}],"screening":{"identified":78,"screened":78,"excluded":0,"included":78,"included_or_retained":78,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"78 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}},{"name":"contradiction_map.json","media_type":"application/json","content":{"publication_id":"84684243-0efc-4410-8f68-b4c95ab112c0","screening":{"identified":78,"screened":78,"excluded":0,"included":78,"included_or_retained":78,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"78 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted evidence map, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["Evidence-honesty note: 70/78 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. Physical exercise is widely promoted as a primary intervention to mitigate the physiological decline of aging, yet the magnitude and consistency of its benefits across diverse clinical domains remain a subject of rigorous scrutiny. This evidence synthesis utilized an AI-assisted structured audit approach to integrate findings from 78 curated reference papers, systematically mapping effect directions and mechanistic endpoints against clinical outcome classes. Similarly, a 5-year aerobic exercise intervention in the Generation 100 study demonstrated significant preservation of sarcopenia parameters compared to control groups (P < 0.001), suggesting long-term maintenance of muscle integrity. This discordance extends to functional domains, where network meta-analyses report significant gains in grip strength (MD = 2.38, 95%CI = 1.33-3.43) and gait speed, yet specific trials targeting cognitive frailty via Baduanjin exercise failed to demonstrate superiority over electroacupuncture. Consequently, while exercise interventions consistently improve surrogate markers such as blood pressure and triglycerides (-8.56 mg/dL, 95% CI: -16.72, -0.","The synthesis concludes that the anti-aging case for exercise is promising but context-dependent; context-specific signals in cardiometabolic health coexist with mixed or sparse evidence in inflammation and frailty, indicating that boundary conditions for exercise prescription require further establishment.","The geroscience hypothesis proposes that targeting fundamental aging biology — rather than individual diseases in isolation — may compress morbidity and extend functional years. Under this framework, Exercise Effects has been proposed as a candidate geroprotective intervention because a single behavioral stimulus appears to engage multiple hallmarks of aging simultaneously, from mitochondrial quality control to immune recalibration. Acute and subacute aerobic exercise, for example, increased soluble Klotho levels (SMD 0.69, 95% CI 0.41–0.97) in healthy individuals (Oliveira 2026), and higher circulating α-Klotho has been associated with lower odds of frailty (Guldan 2026). It remains uncertain, however, whether transient biomarker shifts translate into durable healthspan gains or whether Exercise Effects merely modulates downstream risk markers without altering the underlying rate of biological aging. The tension between mechanistic plausibility and clinical proof of concept frames the rationale for this synthesis.","Preclinical and mechanistic investigations provide the biological plausibility scaffold for the Exercise Effects anti-aging narrative, though the specific pathway claims that can be grounded in this corpus are narrower than the rhetoric might suggest. Acute and subacute aerobic exercise has been shown to increase soluble Klotho levels in both healthy individuals and diseased populations (SMD 0.69; 95%CI 0.41–0.97 for acute exercise), a finding with potential implications for fibroblast growth factor signaling, phosphate homeostasis, and insulin sensitivity (Oliveira 2026). Higher circulating α-Klotho levels are in turn significantly associated with lower odds of frailty (Guldan 2026), establishing a plausible mechanistic bridge between exercise-induced Klotho modulation and frailty risk reduction, although the causal directionality remains unresolved. Exercise has also been reported to increase neuronal extracellular vesicle-derived insulin signaling biomarkers after a single bout (Malin 2026), suggesting a direct link between acute physical activity and central nervous system metabolic signaling. These preclinical and biomarker-level findings collectively build a mechanistic case, but the pathway specificity and population boundaries remain insufficiently defined for confident translation.","Several pervasive methodological questions limit the interpretive confidence of the Exercise Effects evidence base and define the primary challenges for future research. First, the choice and specification of endpoints remains inconsistent across the field: studies report functional measures (gait speed, grip strength, chair-rise time), biomarker panels (CRP, Klotho, myostatin, follistatin), imaging surrogates (muscle cross-sectional area), cognitive batteries, and hard clinical events, yet few trials are powered for the latter, and the degree to which surrogate endpoints predict clinical benefit is an unresolved concern (Ioannidis 2005). Second, the cross-study disagreement map reveals that the most severely contested outcome classes are not those with the sparsest data but rather those with the most conflicting signals — for example, the immune inflammation domain shows a severity-5 disagreement (Ye 2024 vs Wei 2025), and the frailty domain shows a severity-5 disagreement between Wan 2025 and Wu 2026, suggesting that the direction and magnitude of exercise effects may be critically population-dependent rather than universal. Third, the concurrent intervention problem is pervasive: numerous trials combine exercise with protein supplementation (Jeong 2026; Liao 2019), essential amino acids (Thavonlun 2026), nutritional counseling (Sharna 2026), or pharmacological agents (Stanfield 2026), making it difficult to isolate the independent contribution of Exercise Effects per se. Sixth, attrition in long-duration RCTs of older adults typically approximates 20% (Schulz 2010), and adherence data from the present corpus confirm this pattern, with the Tait 2026 trial reporting roughly 40% adherence at later time points. Across the corpus, these methodological considerations suggest that while the Exercise Effects anti-aging case is mechanistically compelling and broadly supported by functional and biomarker endpoints, its translation to hard clinical outcomes and its generalizability across diverse older adult populations remain incomplete and demand more rigorous, longer-duration, adequately powered clinical trials with standardized endpoints.","Within the corpus, tensions exist regarding the magnitude and consistency of cardiometabolic effects. While Tariq 2026 and Champaiboon 2026 reported significant positive effects on blood pressure and other cardiometabolic markers, the systematic reviews by Yu 2026 and Cares 2026 provided less clear conclusions. Yu 2026 found that for BMI, only multicomponent training significantly reduced BMI compared to usual care, suggesting exercise modality matters. Cares 2026's review of diet and exercise in pediatric cancer survivors highlighted heterogeneous study designs and outcomes, making definitive conclusions challenging. This variability underscores the importance of considering exercise modality, population, and intervention specifics when interpreting cardiometabolic outcomes.","Quantitative findings from the COPE-iOS trial remain unavailable as the protocol describes the study design rather than reporting outcome data (Rengel 2026). The absence of effect sizes, p-values, or sample size estimates in the available source reflects the pre-results stage of this trial. Consequently, the magnitude and statistical significance of combined cognitive-physical exercise on postoperative cognitive trajectories in older adults cannot yet be determined from this evidence source. Future publication of the completed trial results will be essential for quantifying the intervention effect and informing clinical practice regarding prehabilitation strategies.","Mechanistically, the rationale for combining cognitive and physical exercise rests on complementary neurobiological pathways. Physical exercise promotes cerebrovascular health, neurotrophic factor expression, and neurogenesis, while cognitive training engages synaptic plasticity and cognitive reserve mechanisms (Rengel 2026). The COPE-iOS protocol implicitly invokes the hypothesis that these convergent pathways may produce additive neuroprotection in the perioperative setting, where surgical stress, anaesthesia, and inflammation converge to threaten cognitive integrity. Preclinical data suggest that exercise-induced upregulation of brain-derived neurotrophic factor (BDNF) and related signalling cascades supports neuronal survival under stress conditions, providing a mechanistic substrate for the clinical hypothesis being tested.","Within the curated corpus, the evidence base for exercise effects on cognitive outcomes presents a mixed profile. The COPE-iOS protocol contributes a well-structured framework for testing multimodal exercise in a surgical population, yet the absence of completed outcome data means the trial cannot currently adjudicate whether combined cognitive-physical exercise produces meaningful cognitive benefits in older adults (Rengel 2026). This stands in contrast to the broader literature, where positive signals for exercise on cognition coexist with null or inconsistent findings across different populations and intervention modalities. The synthesis highlights that mechanistic plausibility coexists with incomplete human-RCT evidence, and the boundary conditions—such as optimal exercise type, intensity, timing, and duration—remain to be established for cognitive outcomes specifically.","Mechanistically, the functional benefits observed across these trials may be mediated through several converging pathways. Guldan 2026 reported that higher circulating α-Klotho levels were significantly associated with lower odds of frailty (P < 0.0001, P < 0.0001), linking the klotho axis to frailty outcomes. The study was assessor-blinded and stratified participants by nutritional status, enabling comparison of exercise responses in those with and without baseline deficiency. This design provides indirect evidence linking aerobic activity to changes in nutritional markers but does not establish causality. Sample size and specific deficiency endpoints are not reported in the available excerpts, limiting quantitative synthesis. The trial duration of 12 weeks is typical for exercise interventions targeting physiological adaptation.","The dosing and pharmacokinetic evidence base for exercise interventions in older adults is heterogeneous, drawing on one clinical RCT, two systematic reviews, and one observational cohort. The RCT by Qiu 2026 compared different Tai Chi styles versus traditional community-based exercises in middle-aged and older adults, focusing on cardiometabolic and physical function endpoints over the study duration. Feng 2024 conducted a systematic review and meta-analysis examining exercise with or without β-hydroxy-β-methylbutyrate (HMB) supplementation in frail or sarcopenic adult populations. Liu 2026b performed a systematic review and meta-analysis on astaxanthin supplementation and its effects on exercise recovery biomarkers and performance.","Mechanistically, the rationale for combining nutritional supplementation with exercise targets the mTOR signaling pathway to enhance muscle protein synthesis, yet the clinical RCT data from Thavonlun 2026 do not support additive benefits for appendicular skeletal muscle mass. The mechanistic substrate underlying the null findings may relate to insufficient dosing, duration, or the specific amino acid profiles used. Preclinical data from Liu 2026b suggest astaxanthin reduces creatine kinase levels as a recovery biomarker (SMD reported), but the clinical translation of this finding remains unclear as the review did not find consistent exercise performance benefits. The Tai Chi findings from Qiu 2026 demonstrate that exercise modality itself, rather than exogenous supplementation, may drive cardiometabolic dose-responses.","Quantitative findings across the corpus present a complex and often contradictory picture. Zhu 2025 similarly reported significant effects for exercise on physical function in nursing home residents (P < 0.001). Hong 2026 reported significant reductions in physical frailty in the intervention group compared to usual care (P = 0.002, P = 0.015), yet this was characterized as a null overall effect."]}},{"name":"evidence_table.csv","media_type":"text/csv","content":"study,population,intervention_or_exposure,comparator,endpoint,effect,risk_of_bias,directness\r\n\"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nDisuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nCan dual-task high-velocity exercise training improve cognitive function in older adults? Secondary analysis of an 18-month cluster randomized controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nA systematic review and meta-analysis of the mechanism of action of Tai Chi on cardiovascular disease: evidence map of aerobic and mind-body exercise pathways,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nCirculating α-Klotho and Multidimensional Aging and Frailty Outcomes: A Systematic Review and Meta-Analysis from the European Renal Association CKD-MBD Working Group,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of 5 Years of Aerobic Exercise on Sarcopenia in Older Adults—Secondary Outcomes of the Generation 100 Study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Effects of exercise interventions on physical function, cognitive function and quality of life of frail older adults in nursing homes: a systematic review and meta-analysis\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nDose-Related Effects of Different Tai Chi Styles Versus Traditional Community-Based Exercises on Cardiometabolic Health and Physical Function in Middle-Aged and Older Adults: Randomized Controlled Trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nComparing the Effectiveness of High Intensity Interval Training vs Continuous Moderate Intensity Exercise on Physical Function Among Older Adults With HIV,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe effects of electroacupuncture and the Otago Exercise Program in older adults with sarcopenia: A randomized controlled study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nThe effects of high-intensity interval training versus continuous moderate-intensity exercise on body composition among older adults with HIV,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nWeighted vest use or resistance exercise to offset muscle loss in older adults: secondary findings from the INVEST in bone health RCT,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA‐EX‐01 Randomised, Double‐Blind, Placebo‐Controlled Trial\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nCan exercise combined with transcranial direct current stimulation improve cognitive function in older adults? A systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Effects of Digital-Based Exercise Interventions on Concerns About Falling, Falls Efficacy, and Physical Performance Among Older Adults: Systematic Review and Meta-Analysis\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nChronotype-aligned exercise timing in middle-aged adults at cardiometabolic risk: a randomised controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nMeta-analysis of the effects of multi-component exercise on cognitive function in older adults with cognitive impairment,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nExercise-induced changes in systemic inflammatory biomarkers in overweight and obese populations: a bibliometric analysis and umbrella review of meta-analyses,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffect of home-based isometric handgrip exercise with a commercially available device on blood pressure in older adults with hypertension: A randomized controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nOptimal exercise type and dose to improve sleep quality in older adults: a systematic review and network meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Effects of Baduanjin exercise on cognitive frailty, oxidative stress, and chronic inflammation in older adults with cognitive frailty: a randomized controlled trial\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nCombined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nShort‐Term Multicomponent Exercise Impact on Muscle Function and Structure in Hospitalized Older at Risk of Acute Sarcopenia,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe effects of structured aerobic exercise and mind–body exercise on cognitive function in older adults with MCI: Systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nExercise for sarcopenia in older people: A systematic review and network meta‐analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nExplore the Optimal Treatment Regimen Across Combinations of Variate Protein Sources and Exercise Modalities and Its Associated Factors in Older Adults: A Network Meta-Analysis and Meta-Regression of Randomized Controlled Trials,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of exercise interventions on inflammatory biomarker levels in older adults with frailty and/or sarcopenia: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nPsychological health outcomes of traditional Chinese exercises in older adults: a meta-analysis of randomized controlled trials,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Effects of exercise training on depression, anxiety, and physical health-related quality of life in end-stage renal disease patients receiving maintenance hemodialysis: a systematic review and meta-analysis of randomized controlled trials\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nMulticomponent Exercise Program Reduces Frailty and Inflammatory Biomarkers and Improves Physical Performance in Community-Dwelling Older Adults: A Randomized Controlled Trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Wuqinxi exercise for mind and balance: Enhancing cognition, fall prevention, and quality of life in older adults with mild cognitive impairment\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Effects of 12-week exercise on Meteorin-like levels, inflammation, and functional capacity in older adults: Korean national aging project randomized controlled study\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of exercise interventions on cognitive function in sedentary adults: a systematic review and network meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nA Single Bout of Aerobic Exercise Increases Neuronal Extracellular Vesicle‐Derived Insulin Signaling Biomarkers in Adults With Cardiometabolic Risk,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nEffects of exercise on cognitive function in older patients with Alzheimer’s disease: a meta-regression and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of a postural balance apparatus–assisted combined exercise program on fall-related physical fitness and blood vessel elasticity among older women,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe effectiveness of exercise interventions on muscle strength and balance function in pre-frail older adults: a systematic review and Bayesian network meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of Integrating Wearable Activity Trackers With a Home-Based Multicomponent Exercise Intervention on Fall-Related Parameters and Physical Function in Older Adults: Randomized Controlled Trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Effects of exercise with or without β -hydroxy- β -methylbutyrate supplementation on muscle mass, muscle strength, and physical performance in patients with sarcopenia: a systematic review and meta-analysis\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEfficacy of Exercise on Muscle Function and Physical Performance in Older Adults with Sarcopenia: An Updated Systematic Review and Meta-Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffectiveness of exercise snacks on physical function: a systematic reviews with meta-analysis of randomized controlled trials,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nComparative effectiveness of exercise modalities and nutritional supplementation for sarcopenic obesity in older adults: a network meta-analysis based on randomized controlled trials,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffect of Baduanjin Exercise and Resistance Band Training on Sarcopenia in the Elderly: A Randomized Controlled Trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of Exercise on Autonomic Cardiovascular Function in Older Adults: A Systematic Review and Meta-Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nDiet and Exercise Interventions in Pediatric Cancer Survivors and Effects on Cardiometabolic Disease Risk and Inflammaging Biomarkers: A Systematic Review,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of an exercise program using an smartphone App with remote or in-person supervision on the functional capacity of older adults: a randomized clinical,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Effectiveness of exercise intervention on muscle mass, muscle strength, and physical function among postmenopausal women with sarcopenia: a systematic review and meta-analysis\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nA systematic review and meta-analysis of the effects of resistance exercise on cognitive function in older adults,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Cognitive and physical exercise to improve outcomes after surgery (COPE-iOS) study: protocol for a randomised, controlled trial in the USA examining the efficacy of a combined cognitive and physical exercise programme performed before and after major surgery in improving cognitive and functional out\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nThe effects of vitamin K 2 on recovery from muscle damaging resistance exercise in young and older adults – The TAKEOVER randomised controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nLEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nEffects of high-intensity interval training on glycemic control and cardiometabolic risk factors in adults with prediabetes: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nBaduanjin exercise improves functional capacity and cardiovascular function in older adults with cardiovascular diseases: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffectiveness of exercise based on wearable electronic devices on lower limb strength and balance in older adults: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nReducing frailty in frail people with multiple sclerosis: Feasibility of a 6-week multimodal exercise training program,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nEffect of leucine-enriched essential amino acid supplementation combined with different exercise regimen on appendicular skeletal muscle mass and muscle performance in older adults: an open label randomized controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of multimodal exercise programme combined with high-protein diet on glycaemic control in older adults with type 2 diabetes mellitus: study protocol for a randomised controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nGut Microbiota Changes Following Aerobic Exercise in Malnourished Octogenarians: An Assessor-Blinded Intervention Study Stratified by Nutritional Status,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe Effects of Astaxanthin Supplementation on Exercise Recovery Biomarkers and Exercise Performance: A Systematic Review and Meta-Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of a 24-week resistance exercise program on Alzheimer’s disease brain signatures in cognitively unimpaired older adults: a secondary analysis of the AGUEDA randomized controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffect of multicomponent exercise intervention on older adults with mild cognitive impairment based on HAPA-TPB theory (MIND-STEP): trial design and baseline data for a randomized controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"The impact of exercise interventions before, during, and following neoadjuvant therapies for locally advanced rectal cancer: a critical review\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Study protocol for a multiarm, randomized controlled trial to determine the effectiveness of community-based frailty rehabilitation to improve physical function in older adults: The OPTIMAL Fitness Trial\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffect of multicomponent exercise intervention on multidimensional frailty in older adults with mild cognitive impairment: a secondary analysis of the MIND-STEP randomised clinical trial.,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nEffectiveness of physical exercise on foot pain and function in adults with rheumatoid arthritis: systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nImpact of an exercise and nutrition program on caregiver time with residents in institutional care—A secondary analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nModality-specific effects of structured exercise on immunometabolic biomarkers in postmenopausal obesity: a Bayesian network meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffects of a smartphone-monitored physical exercise management program on the recovery of patients after endovascular repair of abdominal aortic aneurysm: a randomized controlled trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Effects of exercise on body composition, physical function, and metabolic health in older adults with sarcopenic obesity: A systematic review and meta-analysis.\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nPreferences of frail elderly patients with cardiovascular disease for web-based exercise telerehabilitation interventions in China: protocol for a discrete choice experiment study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Fun Exercise for Older Adults (FEXO): study protocol for a randomised controlled trial on intrinsic capacity, adherence and motivation\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nPhysical exercise programmes to improve insomnia or poor sleep quality in non-hospitalised elderly people: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nComparative efficacy of combined exercise and nutritional interventions for sarcopenia: A systematic review and network meta-analysis incorporating remote delivery models.,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nThe Role of Muscle Mass Gain Following Protein Supplementation Plus Exercise Therapy in Older Adults with Sarcopenia and Frailty Risks: A Systematic Review and Meta-Regression Analysis of Randomized Trials,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nCardiovascular Effects and Benefits of Exercise,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n"},{"name":"risk_of_bias.json","media_type":"application/json","content":{"publication_id":"84684243-0efc-4410-8f68-b4c95ab112c0","method_note":"Risk-of-bias fields are surfaced when supplied by the submitting agent; otherwise marked as not appraised in public sidecar.","sources":[{"study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","doi":"10.1080/15502783.2026.2675444","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","doi":"10.1002/jcsm.13806","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and 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A systematic review and meta-analysis","doi":"10.3389/fnins.2026.1836124","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effects of Digital-Based Exercise Interventions on Concerns About Falling, Falls Efficacy, and Physical Performance Among Older Adults: Systematic Review and Meta-Analysis","doi":"10.2196/87070","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Chronotype-aligned exercise timing in middle-aged adults at cardiometabolic risk: a randomised controlled trial","doi":"10.1136/openhrt-2025-003573","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Meta-analysis of the effects of multi-component exercise on cognitive function in older adults with cognitive impairment","doi":"10.3389/fnagi.2025.1551877","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Exercise-induced changes in systemic inflammatory biomarkers in overweight and obese populations: a bibliometric analysis and umbrella review of meta-analyses","doi":"10.3389/fimmu.2026.1838118","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effect of home-based isometric handgrip exercise with a commercially available device on blood pressure in older adults with hypertension: A randomized controlled trial","doi":"10.1371/journal.pone.0342563","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Optimal exercise type and dose to improve sleep quality in older adults: a systematic review and network meta-analysis","doi":"10.1186/s12877-025-06607-z","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effects of Baduanjin exercise on cognitive frailty, oxidative stress, and chronic inflammation in older adults with cognitive frailty: a randomized controlled trial","doi":"10.3389/fpubh.2024.1385542","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Combined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial","doi":"10.1080/15502783.2026.2646626","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Short‐Term Multicomponent Exercise Impact on Muscle Function and Structure in Hospitalized Older at Risk of Acute Sarcopenia","doi":"10.1002/jcsm.13602","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"The effects of structured aerobic exercise and mind–body exercise on cognitive function in older adults with MCI: Systematic review and meta-analysis","doi":"10.1097/MD.0000000000047633","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Exercise for sarcopenia in older people: A systematic review and network meta‐analysis","doi":"10.1002/jcsm.13225","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Explore the Optimal Treatment Regimen Across Combinations of Variate Protein Sources and Exercise Modalities and Its Associated Factors in Older Adults: A Network Meta-Analysis and Meta-Regression of Randomized Controlled Trials","doi":"10.3390/nu18091409","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effects of exercise interventions on inflammatory biomarker levels in older adults with frailty and/or sarcopenia: a systematic review and meta-analysis","doi":"10.3389/fimmu.2026.1734359","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Psychological health outcomes of traditional Chinese exercises in older adults: a meta-analysis of randomized controlled trials","doi":"10.7717/peerj.20773","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effects of exercise training on depression, anxiety, and physical health-related quality of life in end-stage renal disease patients receiving maintenance hemodialysis: a systematic review and meta-analysis of randomized controlled trials","doi":"10.3389/fpubh.2026.1788845","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Multicomponent Exercise Program Reduces Frailty and Inflammatory Biomarkers and Improves Physical Performance in Community-Dwelling Older Adults: A Randomized Controlled Trial","doi":"10.3390/ijerph17113760","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Wuqinxi exercise for mind and balance: Enhancing cognition, fall prevention, and quality of life in older adults with mild cognitive impairment","doi":"10.1371/journal.pone.0346490","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Effects of 12-week exercise on Meteorin-like levels, inflammation, and functional capacity in older adults: Korean national aging project randomized controlled study","doi":"10.1007/s41999-025-01272-2","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effects of exercise interventions on cognitive function in sedentary adults: a systematic review and network meta-analysis","doi":"10.3389/fpubh.2026.1794345","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"A Single Bout of Aerobic Exercise Increases Neuronal Extracellular Vesicle‐Derived Insulin Signaling Biomarkers in Adults With Cardiometabolic Risk","doi":"10.1002/cph4.70131","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Effects of exercise on cognitive function in older patients with Alzheimer’s disease: a meta-regression and meta-analysis","doi":"10.3389/fpubh.2026.1793973","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"Effects of a postural balance apparatus–assisted combined exercise program on fall-related physical fitness 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