Spermidine is best known for inducing autophagy, the process by which cells break down and recycle damaged proteins and organelles, a mechanism heavily implicated in the lifespan-extending effects of caloric restriction and fasting. Levels decline with age, and supplementation (often from wheat germ extract) has shown lifespan extension across yeast, flies, worms, and rodent models, with human observational data linking higher dietary intake to lower cardiovascular and cancer mortality. It is a favorite in longevity stacks specifically because its mechanism is distinct from and complementary to NAD+ precursors, which work through different pathways entirely.