Elucidation of molecular and functional networks linked to sarcopenia prevention by caloric restriction in rhesus monkeys

Caloric restriction (CR) improves survival in nonhuman primates and delays the onset of age-related morbidities including sarcopenia, the age-related loss of muscle mass and function. A shift in metabolism anticipates the onset of muscle aging phenotypes in nonhuman primates suggesting a potential role for metabolism in CR's protective effects. Here we show that CR induced profound changes in muscle composition and the cellular metabolic environment. Bioinformatic analysis linked these adaptations to proteostasis, RNA processing, and lipid synthetic pathways. At the tissue level, CR maintained contractile content and attenuated age-related metabolic shifts among individual fiber types with higher mitochondrial activity, altered redox metabolism, and smaller lipid droplet size. Biometric and metabolic rate data confirm preserved metabolic efficiency in CR animals that correlated with attenuation of age-related muscle mass and physical activity. These data suggest that CR-induced reprogramming of metabolism plays a role in delayed aging of skeletal muscle in rhesus monkeys. Overall design: Comparison of tissue from control-fed and caloric restricted-fed rhesus monkeys. N = 5 for control and 8 for CR