{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","name":"Bounded Rapamycin signal: rapamycin at 42 ppm extended female median lifespan by 26%","doi":"10.17605/OSF.IO/JQWXC","doi_status":"minted","osf_url":"https://osf.io/jqwxc/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_b1299f8af94f49bb/chain","content_hash":"sha256:dbda1cf0ab331e7fb7f364882c12f410786d548999771d621d6ce1406e311c72","provenance_passport":{"publication_id":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","submission_id":"ab79024d-af3b-4598-ae2d-d050a6832d2d","artifact_type":"alpha_memo","decision":"accept","content_hash":"sha256:dbda1cf0ab331e7fb7f364882c12f410786d548999771d621d6ce1406e311c72","persistent_identifiers":{"doi":"10.17605/OSF.IO/JQWXC","osf_url":"https://osf.io/jqwxc/","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_b1299f8af94f49bb","dw_chain_url":"https://provenance.researka.org/artifacts/claim_b1299f8af94f49bb/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","object_type":"publication","parent_object_id":"ab79024d-af3b-4598-ae2d-d050a6832d2d","title":"Bounded Rapamycin signal: rapamycin at 42 ppm extended female median lifespan by 26%","body_markdown":"**Selected angle:** `source`\n\n## One-sentence thesis\n\nThe cited A/B receipts support a specific working claim: rapamycin at 42 ppm extended female median lifespan by 26%; rapamycin reduced 90th-percentile mortality by 14% in females (Harrison 2009 NIA-ITP, 14 ppm). The cited receipts are separate evidence streams; this memo maps a testable contrast, not one integrated analysis.\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 surprise is bounded to the cited receipt bundle; separate direct sources report measurable effects in female heterogeneous-stock mice (UM-HET3); ITP; female heterogeneous-stock mice (UM-HET3); 4-site NIA Interventions Testing Program cohort; genetically heterogeneous mice (ITP). Treat this as a source-grounded working signal, not a mechanism-wide or topic-wide claim.\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=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/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- `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/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- `fact_id=135475` (`A_core`) — rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206−) ATMs in females doi=10.1093/gerona/glz177\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 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- 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- _Within the currently bound receipt bundle, no A_core/B_context opposing fact was selected. Treat that as a bundle limitation, not a claim that the wider literature has no counter-evidence._\n\n## Next extraction\n\n- Extract independent A_core/B_context receipts that test the lead contrast directly.\n- Audit whether each direct receipt remains comparable on population, endpoint, comparator, and measurement method.\n","metadata":{"abstract":"The cited A/B receipts support a specific working claim: rapamycin at 42 ppm extended female median lifespan by 26%; rapamycin reduced 90th-percentile mortality by 14% in females (Harrison 2009 NIA-ITP, 14 ppm). The cited receipts are separate evidence streams; this memo maps a testable contrast, not one integrated analysis.","article_type":"alpha_memo","counts":{"retrieved_count":5,"selected_count":5,"review_like_count":0,"primary_like_count":5,"year_start":2009,"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","integrity":null,"doi":"10.17605/OSF.IO/JQWXC","doi_status":"minted","osf_status":"minted","osf_project_id":"p8nk6","osf_guid":"jqwxc","osf_url":"https://osf.io/jqwxc/","osf":{"enabled":true,"status":"minted","project_id":"p8nk6","guid":"jqwxc","url":"https://osf.io/jqwxc/","doi":"10.17605/OSF.IO/JQWXC"},"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_b1299f8af94f49bb","dw_chain_url":"https://provenance.researka.org/artifacts/claim_b1299f8af94f49bb/chain","dw_api_chain_url":"https://provenance.researka.org/api/artifacts/claim_b1299f8af94f49bb/chain","dw_source_artifact_id":"source_ae92bde85a0e4871","dw_input_artifact_ids":["source_9d98c8c085a640ac","source_ac3f7edeb0e2422e","source_ec041e11ee784fa9","source_92cc8fab80bc4797","source_1f926627f9b946c9","source_b054369b83494ba6"],"dw_step_id":"step_5bfd78da51fd470a","dw_step_hash":"af24de4bcd7147179683b1a5aae25bb944cd05cf59494596145c1c503de21266","dw_status":"registered","content_hash":"sha256:dbda1cf0ab331e7fb7f364882c12f410786d548999771d621d6ce1406e311c72","sha256":"sha256:dbda1cf0ab331e7fb7f364882c12f410786d548999771d621d6ce1406e311c72"},"created_at":"2026-06-02T14:47:00.454760+04:00"},"sidecars":[{"name":"citation_traces.json","media_type":"application/json","content":{"publication_id":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","traces":[{"claim_id":"claim_1","claim":"The cited A/B receipts support a specific working claim: rapamycin at 42 ppm extended female median lifespan by 26%; rapamycin reduced 90th-percentile mortality by 14% in females (Harrison 2009 NIA-ITP, 14 ppm). The cited receipts are separate evidence streams; this memo maps a testable contrast, not one integrated analysis.","candidate_sources":[{"study":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction","doi":"10.1111/acel.12194","url":null},{"study":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","doi":"10.1038/nature08221","url":null},{"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":null},{"study":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","doi":"10.7554/eLife.16351","url":null},{"study":"Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging","doi":"10.1093/gerona/glz177","url":null}]},{"claim_id":"claim_2","claim":"Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication.","candidate_sources":[{"study":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction","doi":"10.1111/acel.12194","url":null},{"study":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","doi":"10.1038/nature08221","url":null},{"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":null},{"study":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","doi":"10.7554/eLife.16351","url":null},{"study":"Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging","doi":"10.1093/gerona/glz177","url":null}]},{"claim_id":"claim_3","claim":"Bounded research question:** Does the cited receipt bundle still support this bounded claim when population, endpoint, comparator, and time window are aligned?","candidate_sources":[{"study":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction","doi":"10.1111/acel.12194","url":null},{"study":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","doi":"10.1038/nature08221","url":null},{"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":null},{"study":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","doi":"10.7554/eLife.16351","url":null},{"study":"Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging","doi":"10.1093/gerona/glz177","url":null}]},{"claim_id":"claim_4","claim":"`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","candidate_sources":[{"study":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction","doi":"10.1111/acel.12194","url":null},{"study":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","doi":"10.1038/nature08221","url":null},{"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":null},{"study":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","doi":"10.7554/eLife.16351","url":null},{"study":"Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging","doi":"10.1093/gerona/glz177","url":null}]},{"claim_id":"claim_5","claim":"`fact_id=135475` (`A_core`) — rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206−) ATMs in females doi=10.1093/gerona/glz177","candidate_sources":[{"study":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction","doi":"10.1111/acel.12194","url":null},{"study":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","doi":"10.1038/nature08221","url":null},{"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":null},{"study":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","doi":"10.7554/eLife.16351","url":null},{"study":"Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging","doi":"10.1093/gerona/glz177","url":null}]},{"claim_id":"claim_6","claim":"_Within the currently bound receipt bundle, no A_core/B_context opposing fact was selected. 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The cited receipts are separate evidence streams; this memo maps a testable contrast, not one integrated analysis."},{"id":"claim_2","type":"claim","text":"Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication."},{"id":"claim_3","type":"claim","text":"Bounded research question:** Does the cited receipt bundle still support this bounded claim when population, endpoint, comparator, and time window are aligned?"},{"id":"claim_4","type":"claim","text":"`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"},{"id":"claim_5","type":"claim","text":"`fact_id=135475` (`A_core`) — rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206−) ATMs in females doi=10.1093/gerona/glz177"},{"id":"claim_6","type":"claim","text":"_Within the currently bound receipt bundle, no A_core/B_context opposing fact was selected. Treat that as a bundle limitation, not a claim that the wider literature has no counter-evidence._"},{"id":"source_1","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":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":"primary"},{"id":"source_2","type":"source","study":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","year":2009,"doi":"10.1038/nature08221","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":"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":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":"primary"},{"id":"source_4","type":"source","study":"Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice","year":2016,"doi":"10.7554/eLife.16351","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":"primary"},{"id":"source_5","type":"source","study":"Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging","year":2019,"doi":"10.1093/gerona/glz177","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":"primary"}],"edges":[{"from":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","to":"claim_1","type":"contains_claim"},{"from":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","to":"claim_2","type":"contains_claim"},{"from":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","to":"claim_3","type":"contains_claim"},{"from":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","to":"claim_4","type":"contains_claim"},{"from":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","to":"claim_5","type":"contains_claim"},{"from":"48abac66-87ee-46dd-a1e0-1a1bbcc8d12d","to":"claim_6","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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