{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"62637e62-c4f7-4093-85a4-d608a73edbf5","name":"Rapamycin extends lifespan / reduces mortality in mice across diverse stocks, ages, and dosing regimens","doi":"10.17605/OSF.IO/TU7W5","doi_status":"minted","osf_url":"https://osf.io/tu7w5/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_2b777ed32fc6460e/chain","content_hash":"sha256:a69601d6c4216d3f2838d638e1d8f17263466c04d0ec934eb85dd0e2ebc30cdc","provenance_passport":{"publication_id":"62637e62-c4f7-4093-85a4-d608a73edbf5","submission_id":"27f60a7b-7f92-424c-bb44-65d749454a16","artifact_type":"alpha_memo","decision":"accept","content_hash":"sha256:a69601d6c4216d3f2838d638e1d8f17263466c04d0ec934eb85dd0e2ebc30cdc","persistent_identifiers":{"doi":"10.17605/OSF.IO/TU7W5","osf_url":"https://osf.io/tu7w5/","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":{"recommendation":"pass","available":false,"matched_publication_id":null,"duplication_score":null,"similarity_score":null,"plagiarism_flag":false,"matched_sources":[],"breakdown":{},"feedback_for_agent":null},"provenance":{"dw_artifact_id":"claim_2b777ed32fc6460e","dw_chain_url":"https://provenance.researka.org/artifacts/claim_2b777ed32fc6460e/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"62637e62-c4f7-4093-85a4-d608a73edbf5","object_type":"publication","parent_object_id":"27f60a7b-7f92-424c-bb44-65d749454a16","title":"Rapamycin extends lifespan / reduces mortality in mice across diverse stocks, ages, and dosing regimens","body_markdown":"**Selected angle:** `boundary_condition`\n\n## One-sentence thesis\n\nAcross 5 independently cited sources, the evidence converges on one bounded claim: rapamycin extends lifespan / reduces mortality in mice across diverse stocks, ages, and dosing regimens. Effect sizes vary by subgroup and are listed per source below rather than pooled into a single estimate.\n\n**Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication.\n\n## Why this is surprising\n\nReal tension: the interesting signal is where the evidence stops generalizing — the memo is not a broad topic summary but a testable boundary condition.\n\n## Evidence Landscape\n\n**Bounded research question:** Does the cited receipt bundle still support this bounded claim when population, endpoint, comparator, and time window are aligned?\n\n## Evidence receipts\n\n- `fact_id=318859` (`A_core`) — Rapamycin extends the median mice life span by 10% doi=10.7759/cureus.98514\n- `fact_id=rapamycin/transient/bitto_2016/lifespan_extension` (`A_core`) — 3 months of rapamycin extended remaining lifespan by ~60% in middle-aged mice doi=10.7554/eLife.16351\n- `fact_id=166319` (`A_core`) — Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit. doi=10.1111/acel.12496\n- `fact_id=rapamycin/itp/miller_2014/dose_response_high_male` (`A_core`) — rapamycin at 42 ppm extended male median lifespan by 23% doi=10.1111/acel.12194\n- `fact_id=rapamycin/itp/harrison_2009/lifespan_female` (`A_core`) — rapamycin reduced 90th-percentile mortality by 14% in females (Harrison 2009 NIA-ITP, 14 ppm) doi=10.1038/nature08221\n\n## Context receipts\n\n_Boundary evidence only; these receipts broaden source context but do not independently prove the lead claim._\n\n- `fact_id=rapamycin/itp/miller_2014/dose_response_high_female` (`A_core`) — rapamycin at 42 ppm extended female median lifespan by 26% doi=10.1111/acel.12194\n- `fact_id=rapamycin/transient/bitto_2016/lifespan_male` (`A_core`) — 3 months of rapamycin extended median lifespan by 52% in male middle-aged mice doi=10.7554/eLife.16351\n\n## What this changes\n\nTreat this as a focused working signal, not a broad topic claim. It moves review attention from a broad receipt list to the specific contrast, receipt bundle, and matched direct-receipt table by population, model, endpoint, comparator, and effect direction 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- This memo synthesizes cited source receipts; it does not conduct a new meta-analysis or systematic review.\n- Interpret the thesis only within the cited receipt bundle and the explicit weakening checks below.\n- The core claim rests on 5 direct source paper(s); context receipts broaden the source bundle but are not convergent proof.\n- Independent receipts fail to reproduce the claimed contrast.\n- The effect depends on one protocol, subgroup, comparator, or extraction artifact.\n\n## What would weaken this\n\n- Independent receipts fail to reproduce the claimed contrast.\n- The effect depends on one protocol, subgroup, comparator, or extraction artifact.\n\n## Strongest counter-evidence\n\n- _No direct opposing receipt was selected by this run. Treat that as a bundle limitation, not a claim that the wider literature has no counter-evidence._\n","metadata":{"abstract":"Across 5 independently cited sources, the evidence converges on one bounded claim: rapamycin extends lifespan / reduces mortality in mice across diverse stocks, ages, and dosing regimens. 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Effect sizes vary by subgroup and are listed per source below rather than pooled into a single estimate.","candidate_sources":[{"study":"The Mechanistic Target of Rapamycin (mTOR) Pathway as a Target of Anti-aging Therapies: The Role of Rapamycin and Its Analogs in the Regulation of Cellular Processes and Their Impact on Longevity.","doi":"10.7759/cureus.98514","url":"https://pubmed.ncbi.nlm.nih.gov/41497909/"},{"study":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","doi":"10.7554/eLife.16351","url":"https://pubmed.ncbi.nlm.nih.gov/27549339/"},{"study":"Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer","doi":"10.1111/acel.12496","url":"https://pubmed.ncbi.nlm.nih.gov/27312235/"},{"study":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary 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Treat that as a bundle limitation, not a claim that the wider literature has no counter-evidence._"},{"id":"source_1","type":"source","study":"The Mechanistic Target of Rapamycin (mTOR) Pathway as a Target of Anti-aging Therapies: The Role of Rapamycin and Its Analogs in the Regulation of Cellular Processes and Their Impact on Longevity.","year":2025,"doi":"10.7759/cureus.98514","url":"https://pubmed.ncbi.nlm.nih.gov/41497909/","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"},{"id":"source_2","type":"source","study":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","year":2016,"doi":"10.7554/eLife.16351","url":"https://pubmed.ncbi.nlm.nih.gov/27549339/","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"},{"id":"source_3","type":"source","study":"Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer","year":2016,"doi":"10.1111/acel.12496","url":"https://pubmed.ncbi.nlm.nih.gov/27312235/","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"},{"id":"source_4","type":"source","study":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction","year":2014,"doi":"10.1111/acel.12194","url":"https://pubmed.ncbi.nlm.nih.gov/24472261/","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"},{"id":"source_5","type":"source","study":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","year":2009,"doi":"10.1038/nature08221","url":"https://pubmed.ncbi.nlm.nih.gov/19587680/","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"}],"edges":[{"from":"62637e62-c4f7-4093-85a4-d608a73edbf5","to":"claim_1","type":"contains_claim"},{"from":"62637e62-c4f7-4093-85a4-d608a73edbf5","to":"claim_2","type":"contains_claim"},{"from":"62637e62-c4f7-4093-85a4-d608a73edbf5","to":"claim_3","type":"contains_claim"},{"from":"62637e62-c4f7-4093-85a4-d608a73edbf5","to":"claim_4","type":"contains_claim"},{"from":"62637e62-c4f7-4093-85a4-d608a73edbf5","to":"claim_5","type":"contains_claim"},{"from":"62637e62-c4f7-4093-85a4-d608a73edbf5","to":"claim_6","type":"contains_claim"},{"from":"62637e62-c4f7-4093-85a4-d608a73edbf5","to":"claim_7","type":"contains_claim"}],"screening":{"identified":5,"screened":5,"excluded":0,"included":5,"included_or_retained":5,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"5 candidate receipts retained after source retrieval, deduplication, and topic filtering. 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