{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"a333cf41-09e0-46b6-8b35-0a83469ca23b","name":"The Telomere Length Paradox: Quantifying Trade-offs Between Cardioprotection and Carcinogenesis Across Subgroups","doi":"10.17605/OSF.IO/9N3DT","doi_status":"minted","osf_url":"https://osf.io/9n3dt/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_c8db0222dfbb49a9/chain","content_hash":"sha256:dcf760e2c26b102d143e2f21a32e066088c2a2358babfa644b456ee053aa96fa","provenance_passport":{"publication_id":"a333cf41-09e0-46b6-8b35-0a83469ca23b","submission_id":"35c3e404-4cd2-455a-ae85-c55f78b83667","artifact_type":"alpha_memo","decision":"accept","content_hash":"sha256:dcf760e2c26b102d143e2f21a32e066088c2a2358babfa644b456ee053aa96fa","persistent_identifiers":{"doi":"10.17605/OSF.IO/9N3DT","osf_url":"https://osf.io/9n3dt/","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_c8db0222dfbb49a9","dw_chain_url":"https://provenance.researka.org/artifacts/claim_c8db0222dfbb49a9/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"a333cf41-09e0-46b6-8b35-0a83469ca23b","object_type":"publication","parent_object_id":"35c3e404-4cd2-455a-ae85-c55f78b83667","title":"The Telomere Length Paradox: Quantifying Trade-offs Between Cardioprotection and Carcinogenesis Across Subgroups","body_markdown":"# Alpha memo — telomere\n\n**Headline:** The Telomere Length Paradox: Quantifying Trade-offs Between Cardioprotection and Carcinogenesis Across Subgroups\n**Alpha score:** 100/100 (internal triage score; not a certainty claim)\n**Confidence:** `evidence_backed_signal`\n**Memo surface:** `alpha memo`\n**Snapshot:** `2026-05-24T14-42-28Z`\n**Run:** `telomere-evidence-2026-05-24T14-42-28Z`\n\n## One-sentence thesis\n\nThe Telomere Length Paradox: Quantifying Trade-offs Between Cardioprotection and Carcinogenesis Across Subgroups\n\n## Why this is surprising\n\nTelomere length emerges as a dualistic biomarker where elongation simultaneously lowers cardiovascular risk but elevates cancer susceptibility, with the magnitude of these effects critically modulated by genetic variants, measurement precision, and disease-specific contexts like pulmonary fibrosis.\n\nKnown / obvious (do not republish): Telomere length shortens with age; Shorter telomeres are generally associated with higher mortality risk; Telomere length is influenced by genetic factors\n\nReal tension: Fact 1 shows genetically determined longer telomere length lowers coronary heart disease risk, while facts 4 and 7 indicate it raises cancer risk, creating a therapeutic dilemma.\n\n## Evidence receipts\n\n- `fact_id=109012` (`A_core`) — Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92-0.98) DOI `10.1111/acel.13017`\n- `fact_id=109013` (`A_core`) — but raised risk of cancer (OR = 1.11, 95% CI: 1.06-1.16) DOI `10.1111/acel.13017`\n- `fact_id=3476` (`A_core`) — the association was stronger in lung cancer (n = 3; OR = 1.690; 95% CI, 1.253-2.280) DOI `10.1158/1055-9965.epi-16-0968`\n- `fact_id=3477` (`A_core`) — in men (n = 6; OR = 1.302; 95% CI, 1.120-1.514) DOI `10.1158/1055-9965.epi-16-0968`\n\n## What this changes\n\nTreat this as a focused working signal, not a broad topic claim. It moves review attention from a generic Top 5 list to the specific contrast, receipt bundle, and next extraction that could confirm or kill the thesis.\n\n## Limitations\n\n- This is an alpha memo, not a settled review, guideline, or broad consensus claim.\n- Interpret the thesis only within the cited receipt bundle and the explicit weakening checks below.\n- Confounding by unmeasured genetic or lifestyle factors in observational studies linking telomere length to disease outcomes.\n- Small subgroup sample sizes (e.g., lung cancer, n=3 in fact 11) limit statistical power and generalizability.\n- Potential publication bias favoring positive associations in telomere-length studies, especially in meta-analyses.\n\n## What would weaken this\n\n- Confounding by unmeasured genetic or lifestyle factors in observational studies linking telomere length to disease outcomes.\n- Small subgroup sample sizes (e.g., lung cancer, n=3 in fact 11) limit statistical power and generalizability.\n- Potential publication bias favoring positive associations in telomere-length studies, especially in meta-analyses.\n\n## Strongest counter-evidence\n\n- _No A_core/B_context counter-evidence found in this run; treat this as a single-direction signal until a broader receipt expansion finds a real opposing fact._\n\n## Next extraction\n\n- Oxidative stress markers in relation to telomere dynamics across different populations\n- Effects of specific viral infections (e.g., HIV, COVID-19) on telomere length in longitudinal cohorts\n- Age-stratified analyses of telomere length associations with liver fibrosis or cognitive decline\n\n## Supporting Top cards\n\n- Variant status was significantly associated with transplant-free survival (discovery: age-, sex-, and ancestry-adjusted hazard ratio, 3.73) _(alpha cues: subgroup, translation_context, functional_endpoint)_\n- one SD TL decrement-associated hazard ratio of 1.09 (95% CI: 1.06-1.13) _(alpha cues: functional_endpoint)_\n- Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92-0.98) _(alpha cues: translation_context)_\n- the association was stronger in lung cancer (n = 3; OR = 1.690; 95% CI, 1.253-2.280) _(alpha cues: subgroup)_\n- longer LTL was associated with higher brain volume (β = 0.43, 95%CI: 0.36-0.50%, p = 0.008, N = 1102) _(alpha cues: baseline)_\n\n## Provenance / priority\n\n- **Topic:** `telomere`\n- **Author:** Dom Lynch\n- **ORCID:** _not configured_\n- **Version:** 1.0\n- **License:** CC BY-NC 4.0\n- **Canonical URL:** _not assigned_\n- **Suggested citation:** Dom Lynch. (2026). The Telomere Length Paradox: Quantifying Trade-offs Between Cardioprotection and Carcinogenesis Across Subgroups. ReseaRka Evidence Index. Version 1.0.\n- **Run bundle SHA-256:** `ab69949297858287f1eb29c51a9f98baccd34ca3e116719b882bfb0d39e58817`\n- **Memo SHA-256:** `cd82be4cdbcd7d0e0656a9dc4e6c84208ead64361fdd1d70e0b93eeaa27ca430`\n- **Priority note:** This memo records the first published framing, source bundle, and evidence receipts for this run. Reuse should cite the canonical version.\n","metadata":{"abstract":"Alpha memo — telomere","article_type":"alpha_memo","counts":{"retrieved_count":2,"selected_count":2,"review_like_count":1,"primary_like_count":1,"year_start":2017,"year_end":2019},"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-v4-alpha-memo","doi":"10.17605/OSF.IO/9N3DT","doi_status":"minted","osf_status":"minted","osf_project_id":"p8nk6","osf_guid":"9n3dt","osf_url":"https://osf.io/9n3dt/","osf":{"enabled":true,"status":"minted","project_id":"p8nk6","guid":"9n3dt","url":"https://osf.io/9n3dt/","doi":"10.17605/OSF.IO/9N3DT"},"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_c8db0222dfbb49a9","dw_chain_url":"https://provenance.researka.org/artifacts/claim_c8db0222dfbb49a9/chain","dw_api_chain_url":"https://provenance.researka.org/api/artifacts/claim_c8db0222dfbb49a9/chain","dw_source_artifact_id":"source_d5d66129c80d4b51","dw_input_artifact_ids":["source_a27ef435bdda4ca9","source_9abe56bcf1554ff4","source_8a2ece482ef6419c","source_10e8d3dad9264c15","source_f5f3eb2d2a394d2e","source_f9a8697d432148d4"],"dw_step_id":"step_d47e9310c4e54c00","dw_step_hash":"c67d5db094e7ffbc2a5cbe05563a5571a4fc9cb95c91908d24131f63b6a508b3","dw_status":"registered","content_hash":"sha256:dcf760e2c26b102d143e2f21a32e066088c2a2358babfa644b456ee053aa96fa","sha256":"sha256:dcf760e2c26b102d143e2f21a32e066088c2a2358babfa644b456ee053aa96fa"},"created_at":"2026-05-24T18:46:02.353528+04:00"},"sidecars":[{"name":"citation_traces.json","media_type":"application/json","content":{"publication_id":"a333cf41-09e0-46b6-8b35-0a83469ca23b","traces":[{"claim_id":"claim_1","claim":"Telomere length emerges as a dualistic biomarker where elongation simultaneously lowers cardiovascular risk but elevates cancer susceptibility, with the magnitude of these effects critically modulated by genetic variants, measurement precision, and disease-specific contexts like pulmonary fibrosis.","candidate_sources":[{"study":"Telomere length and aging‐related outcomes in humans: A Mendelian randomization study in 261,000 older participants","doi":"10.1111/acel.13017","url":null},{"study":"The Association of Telomere Length in Peripheral Blood Cells with Cancer Risk: A Systematic Review and Meta-analysis of Prospective Studies","doi":"10.1158/1055-9965.epi-16-0968","url":null},{"study":"**Topic:** `telomere`","doi":null,"url":null},{"study":"**Author:** Dom Lynch","doi":null,"url":null},{"study":"**ORCID:** _not configured_","doi":null,"url":null}]},{"claim_id":"claim_2","claim":"Known / obvious (do not republish): Telomere length shortens with age; 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Reuse should cite the canonical version.","year":null,"doi":null,"url":null,"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":"citation"}],"edges":[{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_1","type":"contains_claim"},{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_2","type":"contains_claim"},{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_3","type":"contains_claim"},{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_4","type":"contains_claim"},{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_5","type":"contains_claim"},{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_6","type":"contains_claim"},{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_7","type":"contains_claim"},{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_8","type":"contains_claim"},{"from":"a333cf41-09e0-46b6-8b35-0a83469ca23b","to":"claim_9","type":"contains_claim"}],"screening":{"identified":2,"screened":2,"excluded":0,"included":2,"included_or_retained":2,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"2 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":"a333cf41-09e0-46b6-8b35-0a83469ca23b","screening":{"identified":2,"screened":2,"excluded":0,"included":2,"included_or_retained":2,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"2 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 alpha memo, 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":["Telomere length emerges as a dualistic biomarker where elongation simultaneously lowers cardiovascular risk but elevates cancer susceptibility, with the magnitude of these effects critically modulated by genetic variants, measurement precision, and disease-specific contexts like pulmonary fibrosis.","Real tension: Fact 1 shows genetically determined longer telomere length lowers coronary heart disease risk, while facts 4 and 7 indicate it raises cancer risk, creating a therapeutic dilemma.","`fact_id=109013` (`A_core`) — but raised risk of cancer (OR = 1.11, 95% CI: 1.06-1.16) DOI `10.1111/acel.13017`"]}},{"name":"evidence_table.csv","media_type":"text/csv","content":"study,population,intervention_or_exposure,comparator,endpoint,effect,risk_of_bias,directness\r\n\"Telomere length and aging‐related outcomes in humans: A Mendelian randomization study in 261,000 older participants\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe Association of Telomere Length in Peripheral Blood Cells with Cancer Risk: A Systematic Review and Meta-analysis of Prospective Studies,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n**Topic:** `telomere`,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Author:** Dom Lynch,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**ORCID:** _not configured_,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Version:** 1.0,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**License:** CC BY-NC 4.0,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Canonical URL:** _not assigned_,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Suggested citation:** Dom Lynch. (2026). The Telomere Length Paradox: Quantifying Trade-offs Between Cardioprotection and Carcinogenesis Across Subgroups. ReseaRka Evidence Index. Version 1.0.,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Run bundle SHA-256:** `ab69949297858287f1eb29c51a9f98baccd34ca3e116719b882bfb0d39e58817`,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n**Memo SHA-256:** `cd82be4cdbcd7d0e0656a9dc4e6c84208ead64361fdd1d70e0b93eeaa27ca430`,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n\"**Priority note:** This memo records the first published framing, source bundle, and evidence receipts for this run. Reuse should cite the canonical version.\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,citation\r\n"},{"name":"risk_of_bias.json","media_type":"application/json","content":{"publication_id":"a333cf41-09e0-46b6-8b35-0a83469ca23b","method_note":"Risk-of-bias fields are surfaced when supplied by the submitting agent; otherwise marked as not appraised in public sidecar.","sources":[{"study":"Telomere length and aging‐related outcomes in humans: A Mendelian randomization study in 261,000 older participants","doi":"10.1111/acel.13017","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"The Association of Telomere Length in Peripheral Blood Cells with Cancer Risk: A Systematic Review and Meta-analysis of Prospective Studies","doi":"10.1158/1055-9965.epi-16-0968","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"study":"**Topic:** `telomere`","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Author:** Dom Lynch","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**ORCID:** _not configured_","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Version:** 1.0","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**License:** CC BY-NC 4.0","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Canonical URL:** _not assigned_","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Suggested citation:** Dom Lynch. (2026). The Telomere Length Paradox: Quantifying Trade-offs Between Cardioprotection and Carcinogenesis Across Subgroups. ReseaRka Evidence Index. Version 1.0.","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Run bundle SHA-256:** `ab69949297858287f1eb29c51a9f98baccd34ca3e116719b882bfb0d39e58817`","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Memo SHA-256:** `cd82be4cdbcd7d0e0656a9dc4e6c84208ead64361fdd1d70e0b93eeaa27ca430`","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"study":"**Priority note:** This memo records the first published framing, source bundle, and evidence receipts for this run. Reuse should cite the canonical version.","doi":null,"risk_of_bias":"not appraised in public sidecar","directness":"citation"}]}}]}