Rapamycin

The only drug to consistently extend lifespan in mice when started even at older ages. Human longevity trials are ongoing but the immunosuppressive trade-off remains the central challenge.

A rough internal score reflecting quantity, quality, and consistency of human evidence. Not a clinical recommendation.

Extended lifespan in mice by 10–25% across multiple studies (ITP program). Mechanism involves mTOR Complex 1 inhibition, enhancing autophagy, reducing cellular senescence, and improving stem cell function. Human data for longevity is limited to biomarker studies and the PEARL trial. Intermittent dosing may preserve immune function while retaining benefits.

• Consistent lifespan extension across species in controlled studies
• FDA-approved with well-understood pharmacology
• Enhances autophagy and reduces cellular senescence

Transplant: 2–5 mg/day (trough-guided). Longevity community: 3–6 mg once weekly (investigational, not FDA-approved for this use).

• Mouth ulcers
• Dyslipidemia
• Impaired wound healing
• Immunosuppression
• Insulin resistance

Immunosuppression at chronic doses. Mouth ulcers, impaired wound healing, dyslipidemia, and insulin resistance. Requires monitoring of lipids, glucose, and CBC.

Mouse lifespan extension is robust but translation to human healthspan/lifespan is unproven. Optimal dosing schedule for longevity versus immunosuppression is still being researched.

• Longevity70
• Immunity30