Rapamycin is one of only two interventions — alongside caloric restriction — that has ever extended lifespan across all four model-organism categories tested by the Interventions Testing Program (ITP) (yeast, worms, flies, mammals), and shows uniform life extension unmatched by any other molecule tested. It acts on mTOR, a pathway robustly expressed from infancy through puberty — one of the most rapid aging phases of life — that tapers off after puberty, consistent with the framing that 'development is aging.'
Dosing and side effects: Peter Attia takes 8 mg once weekly, cycling roughly two months on and one month off due to side effects (~10% of his rapamycin patients develop mouth sores). It is off-patent and inexpensive (~$40/week at a therapeutic geroprotective dose), which the source frames as explaining the comparative lack of marketing/hype around it relative to heavily promoted NAD precursor products (see NAD Precursor Supplementation (NR, NMN, IV NAD)).
Immune effects flip with dosing schedule: taken daily, rapamycin appears immunosuppressive (consistent with its origin in transplant medicine). But pulsed weekly dosing — per Mannick & Klickstein's 2014 study on elderly subjects and flu vaccine response — appears to enhance immune function instead. This reframes rapamycin as an immune modulator rather than a pure suppressant, with dosing schedule (not just total dose) as the operative variable.
Sits in Attia's three-category framework (see Longevity Intervention Classification Frameworks) as a 'geroprotective molecule' — one that targets aging hallmarks directly, distinct from behavioral factors or disease-specific drugs.
Caloric restriction and rapamycin are the only two known non-genetic interventions shown to extend lifespan across yeast, worms, flies, and mammals, both acting by downregulating mTOR — see Caloric Restriction & the Sirtuin Hypothesis for the caloric-restriction side. This is contrasted with mTOR activation in skeletal muscle, which is desirable locally even though chronic systemic activation may be harmful; the goal is framed as activating mTOR locally via exercise plus leucine/protein rather than suppressing or activating it systemically (see Leucine).
Translatability caveat: rapamycin's dramatic lifespan extension in mice may not scale proportionally to humans. Per the 'longevity quotient' framework (body-size-predicted lifespan vs. actual lifespan across species, attributed to Eric Verdin), mice live far below their predicted ceiling, while humans are already near their ~80-year predicted ceiling — leaving less theoretical room for a similar-magnitude effect. Human resistance-training studies also found rapamycin blunted muscle protein synthesis, a direct tension with the muscle-preservation goals covered in Daily Protein Intake Guidelines and Training to Failure & Stimulus-to-Fatigue Ratio. (Drive Podcast ep. 369, Attia/Galpin.)
Из тем: Longevity Interventions