Caloric restriction

Caloric restriction is a sustained reduction in energy intake, typically 10–30% below ad libitum, without malnutrition. It activates conserved nutrient-sensing pathways including AMPK and sirtuins while suppressing mTOR and insulin/IGF-1 signaling. In many rodent models it extends lifespan, though effects vary by strain, sex, age at onset, and protocol; non-human primate trials gave divergent results (Wisconsin vs. NIA). In humans, the CALERIE-2 trial (~12% achieved restriction, below the 25% target) improved cardiometabolic markers and reduced inflammation.