Evidence Level
Rapamycin is arguably the most validated longevity drug in existence. Harrison et al. (2009) published the landmark ITP study showing lifespan extension in mice even at late-life initiation. Mannick et al. (2014) made the counterintuitive discovery that low-dose mTOR inhibition enhanced immune function in the elderly — a finding that reshaped thinking about rapamycin's risk profile. Blagosklonny has published extensively on the theoretical framework for rapamycin as an anti-aging drug, arguing that aging is driven by mTOR hyperfunction. Matt Kaeberlein's Dog Aging Project is testing rapamycin in companion dogs as a stepping stone to human longevity trials. The key innovation in longevity use is intermittent (weekly) rather than daily dosing, which appears to preserve immune function while still providing mTOR inhibition benefits. This is a potent pharmaceutical requiring expert medical supervision.