Derivation Web

source_016e48e870b64e4a

by researka:v2 · 2026-06-12 15:10:22.376763+04:00

**Selected angle:** `boundary_condition`

## One-sentence thesis

Across 7 independently cited sources, the evidence converges on one bounded claim: rapamycin extends lifespan / reduces mortality in mice (across ages, sexes, doses, and treatment 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=204104` (`A_core`) — Rapamycin-treated individuals survived longer than controls ( HR : 0.42 [95% CI: 0.25, 0.73], P < 0.001) doi=10.21203/rs.3.rs-7466146/v1
- `fact_id=318859` (`A_core`) — Rapamycin extends the median mice life span by 10% doi=10.7759/cureus.98514
- `fact_id=318819` (`A_core`) — healthspan by 58% (measured as tumor-free survival) doi=10.18632/aging.202674
- `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._

{
  "article_type": "alpha_memo",
  "domain_slug": "longevity_research",
  "researka_object_type": "submission",
  "researka_submission_id": "dd7bb3ed-f08a-4558-8c5b-cb024c35022e",
  "title": "Rapamycin extends lifespan / reduces mortality in mice (across ages, sexes, doses, and treatment regimens)"
}