Anabolic resistance

Anabolic resistance is the age-associated blunting of muscle protein synthesis (MPS) in response to protein ingestion and resistance exercise. In young adults, roughly 20–25 g of protein per meal saturates postprandial MPS; older muscle requires substantially more leucine, with thresholds estimated at 35–40 g per sitting. Underlying defects include attenuated phosphorylation of mTORC1 effectors p70S6K1 and 4E-BP1, increased splanchnic retention of dietary amino acids, impaired amino acid transport, low-grade chronic inflammation, and reduced satellite-cell responsiveness. Cuthbertson et al. (2005, FASEB Journal) showed these nodes to be significantly less phosphorylated in older versus younger muscle after matched amino acid infusion. Wall et al. (2015, PLOS ONE) found MPS 16 % lower in older men (~75 y) than young men (~22 y), with more than threefold less relative responsiveness to dietary protein. Anabolic resistance is a primary driver of sarcopenia and of the decline in muscle quality that predicts falls and all-cause mortality. Evidence from stable-isotope tracer studies supports protein intake of ≥1.2 g/kg/day in older adults, distributed across meals and combined with resistance exercise; whether these strategies fully reverse the deficit remains under investigation.