Longevity & AgingmTOR vs AMPK: The Molecular Tug-of-War That Shapes Muscle and Longevity
Skeletal muscle mass depends on a dynamic balance between mTOR, which drives protein synthesis and hypertrophy, and AMPK, which promotes autophagy, mitochondrial biogenesis, and energy conservation. This 2025 narrative review synthesizes human trials and mechanistic studies to show that chronic mTOR hyperactivation raises risk for obesity, insulin resistance, neurodegeneration, and cancer, while strategic AMPK activation counterbalances those harms. Practical recommendations include ~1.6 g/kg/day total protein distributed evenly across meals, leucine-rich sources like whey for maximal mTOR stimulation, and periodic AMPK activation through aerobic training or intermittent fasting. Older adults benefit from higher per-meal doses (~0.40 g/kg) to overcome anabolic resistance. Neither pathway should dominate; the optimal state cycles between anabolic building and catabolic renewal.
