Rapamycin extends lifespan / reduces mortality in mice across diverse stocks, ages, and dosing regimens

Selected angle: boundary_condition

One-sentence thesis

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. Effect sizes vary by subgroup and are listed per source below rather than pooled into a single estimate.

Interpretation note: This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication.

Why this is surprising

Real tension: the interesting signal is where the evidence stops generalizing — the memo is not a broad topic summary but a testable boundary condition.

Evidence Landscape

Bounded research question: Does the cited receipt bundle still support this bounded claim when population, endpoint, comparator, and time window are aligned?

Evidence receipts

• fact_id=318859 (A_core) — Rapamycin extends the median mice life span by 10% doi=10.7759/cureus.98514
• 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
• 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
• 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
• 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

Context receipts

Boundary evidence only; these receipts broaden source context but do not independently prove the lead claim.

• 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
• 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

What this changes

Treat 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.

Limitations

• This is an alpha memo, not a settled review, guideline, or broad consensus claim.
• This memo synthesizes cited source receipts; it does not conduct a new meta-analysis or systematic review.
• Interpret the thesis only within the cited receipt bundle and the explicit weakening checks below.
• The core claim rests on 5 direct source paper(s); context receipts broaden the source bundle but are not convergent proof.
• Independent receipts fail to reproduce the claimed contrast.
• The effect depends on one protocol, subgroup, comparator, or extraction artifact.

What would weaken this

• Independent receipts fail to reproduce the claimed contrast.
• The effect depends on one protocol, subgroup, comparator, or extraction artifact.

Strongest counter-evidence

• 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.