“Rapamycin is the most promising anti-aging drug”

## The Animal Evidence The NIA Interventions Testing Program (ITP) — a rigorous multi-site mouse longevity program — showed rapamycin extends lifespan by 14–26% in both male and female mice, even when started at age equivalent to 60 years in humans. This is the most replicated pharmacological lifespan extension in mammals to date. Mechanistically, rapamycin inhibits mTORC1 (mechanistic target of rapamycin), a central regulator of cellular growth, protein synthesis, and autophagy. mTOR inhibition mimics aspects of caloric restriction. ## The Human Picture Rapamycin is FDA-approved for organ transplant rejection prevention and certain cancers. At these doses, it is immunosuppressive. Low-dose or intermittent dosing (as being explored for anti-aging) may preserve longevity benefits with reduced immunosuppression, but this is speculative. PEARL trial (targeting Alzheimer's prevention), TRIAD trial (healthy aging), and several other human longevity trials are underway as of 2024. No longevity data in healthy humans exists yet. ## The Risk Picture Side effects include impaired wound healing, dyslipidemia, glucose dysregulation, and increased infection susceptibility. The benefit/risk calculation for healthy humans remains entirely unclear without human RCT data.