Rapamycin

Rapamycin is the most consistently validated pharmacological longevity intervention, extending mouse lifespan by 9–14% even when started late in life, as shown in the NIA Interventions Testing Program. Its mechanism—inhibiting mTOR to shift cells from growth to maintenance—upregulates autophagy and targets four aging hallmarks. The PEARL trial (PMC12074816) demonstrated safety and improved lean tissue mass in women on intermittent low-dose rapamycin (5–10 mg once weekly) over 48 weeks. Compared to (NMN/NMNH), Rapamycin has stronger mouse lifespan data but a narrower mechanistic scope, focusing on nutrient sensing and autophagy. Biohackers use weekly dosing to avoid immunosuppression seen at transplant doses, though side effects like mouth sores and mild lipid changes occur in about 20% of users.