Late-Onset Caloric Restriction Alters Skeletal Muscle Metabolism: Mechanisms from Animal and Human Studies

Skeletal muscle is an organ critical for generating movement and fueling metabolism. Age-related muscle dysfunction, including loss of muscle mass and strength, not only impairs elder persons' physical function but also decreases their peripheral insulin sensitivity. The key contributor to the age-related muscle dysfunction is impaired mitochondrial function. Mitochondrial dysfunction results in the alteration of cellular metabolic patterns away from mitochondrial respiration and toward glycolysis, which decreases cells' energy-generation capacity. In addition, impaired mitochondria release more free radicals, which increases cellular oxidative stress and protein oxidative modification and degradation. Caloric restriction (CR), with the characteristic of boosting cellular antioxidant capacity, was found beneficial for aging skeletal muscles. CR has been shown to retard age-related muscle loss, increase muscle antioxidant capacity, decrease muscle oxidative stress, improve muscle mitochondrial function, improve muscle insulin sensitivity and glucose uptake, and reprogram skeletal muscle metabolism from glycolysis to mitochondrial oxidative phosphorylation. In summary, CR provides beneficial effects on aging skeletal muscles partly by decreasing oxidative stress and modulating cellular metabolism.