Abstract Skeletal muscle is the organ of locomotion, its optimal function is critical for athletic performance, and is also important for health due to its contribution to resting metabolic rate and as a site for glucose uptake and storage. Numerous endogenous and exogenous factors influence muscle mass. Much of what is currently known regarding muscle protein turnover is owed to the development and use of stable isotope tracers. Skeletal muscle mass is determined by the meal‐ and contraction‐induced alterations of muscle protein synthesis and muscle protein breakdown. Increased loading as resistance training is the most potent nonpharmacological strategy by which skeletal muscle mass can be increased. Conversely, aging (sarcopenia) and muscle disuse lead to the development of anabolic resistance and contribute to the loss of skeletal muscle mass. Nascent omics‐based technologies have significantly improved our understanding surrounding the regulation of skeletal muscle mass at the gene, transcript, and protein levels. Despite significant advances surrounding the mechanistic intricacies that underpin changes in skeletal muscle mass, these processes are complex, and more work is certainly needed. In this article, we provide an overview of the importance of skeletal muscle, describe the influence that resistance training, aging, and disuse exert on muscle protein turnover and the molecular regulatory processes that contribute to changes in muscle protein abundance. © 2021 American Physiological Society. Compr Physiol 11:2249‐2278, 2021.
Didactic Synopsis Major Teaching Points Muscle mass is dictated by two dynamic processes—muscle protein synthesis (MPS) and breakdown (MPB)—and changes to MPS govern, in most healthy persons, changes in muscle mass. Muscle mass is regulated by a host of endogenous and exogenous factors. Resistance training (RT) is the most potent nonpharmacological intervention capable of increasing MPS, skeletal muscle mass, and function. Aging and disuse have deleterious consequences for skeletal muscle mass and function. 'Omics‐based technologies and stable isotope tracers have substantially advanced our understanding of exercise‐, aging‐, and disuse‐induced changes in skeletal muscle regulation.