Starved to Life?: Caloric restriction—reducing the calories ingested by around 30% of that of a normal, fit individual—leads to substantial increases in life span in experimental animals. In an extensive study of caloric restriction in primates, Colman et al. (p. 201 ) report that rhesus monkeys, which were subjected to caloric restriction as adults and followed for the last 20 years, show decreased mortality and delayed onset of age-related diseases when compared to normally fed control animals. If compliance with such a diet were not so difficult, many humans would be strongly tempted to enjoy the decreased incidence of brain degeneration, cardiovascular disease, diabetes, and cancer apparent in this population of monkeys.

Sarcopenia, the loss of muscle mass with normal aging, devastates quality of life—and related healthcare expenditures are enormous. The prevention or attenuation of sarcopenia would be an important medical advance. Dietary restriction (DR) is the only dietary intervention that consistently extends median and maximum life span, as well as health span in rodents. Evidence suggests that DR will have a similar effect in primates. Furthermore, DR opposes sarcopenia in rodents. We tested the hypothesis that DR will reduce age-related sarcopenia in a nonhuman primate. Thirty adult male rhesus monkeys, half fed a normal calorie intake and half reduced by 30% in caloric intake, were examined over 17 years for changes in dual-energy X-ray absorptiometry-estimated skeletal muscle mass. Body weight-adjusted skeletal muscle mass declined somewhat in both groups but was far more rapid in the control group. We have shown that moderate, adult-onset DR can attenuate sarcopenia in a nonhuman primate model.

Summary: Age‐associated skeletal muscle mass loss curtails quality of life and may contribute to defects in metabolic homeostasis in older persons. The onset of sarcopenia occurs in middle age in rhesus macaques although the trigger has yet to be identified. Here, we show that a shift in metabolism occurs in advance of the onset of sarcopenia in rhesus vastus lateralis. Multiphoton laser‐scanning microscopy detects a shift in the kinetics of photon emission from autofluorescent metabolic cofactors NADH and FAD. Lifetime of both fluorophores is shortened at mid‐age, and this is observed in both free and bound constituent pools. Levels of FAD and free NADH are increased and the NAD/NADH redox ratio is lower. Concomitant with this, expression of fiber‐type myosin isoforms is altered resulting in a shift in fiber‐type distribution, activity of cytochrome c oxidase involved in mitochondrial oxidative phosphorylation is significantly lower, and the subcellular organization of mitochondria in oxidative fibers is compromised. A regulatory switch involving the transcriptional coactivator PGC‐1α directs metabolic fuel utilization and governs the expression of structural proteins. Age did not significantly impact total levels of PGC‐1α; however, its subcellular localization was disrupted, suggesting that PGC‐1α activities may be compromised. Consistent with this, intracellular lipid storage is altered and there is shift to larger lipid droplet size that likely reflects a decline in lipid turnover or a loss in efficiency of lipid metabolism. We suggest that changes in energy metabolism contribute directly to skeletal muscle aging in rhesus monkeys.