Long-term caloric restriction abrogates the age-related decline in skeletal muscle aerobic function.

The purpose of this study was to determine the effect of long-term caloric restriction (CR) on the age-associated decline of skeletal muscle aerobic function. Skeletal muscle maximal aerobic performance (VO2max) was assessed in ad libitum (AL) and CR rats aged 8-10 months and 35 months using a pump-perfused hindlimb model to match oxygen delivery to muscle mass between groups. Whereas there was a 46% decline in muscle mass-specific VO2max between 8-10 mo (524+/-13 micromol x min(-1) x 100 g(-1); mean+/- SE) and 35 mo (281+/-54 micromol x min(-1) x 100 g(-1)) in AL rats, not only did CR rats begin at the same point in 8-10 mo old rats (490+/-42 micromol x min(-1) x 100 g(-1)), we found no decline in 35 mo old CR animals (484+/-49 micromol x min(-1) x 100 g(-1)). Interestingly, although most markers of oxidative capacity began at a lower point in young adult CR animals, CR rats exhibited a higher in situ activity of complex IV at VO2max. This activity allows the young adult CR animals to exhibit normal aerobic capacity despite the lower oxidative enzyme activities. In stark contrast to the 19-41% decline in activities of citrate synthase, complexes I-III, and complex IV in homogenates prepared from the plantaris muscle and mixed region of gastrocnemius muscle with aging in AL rats, no age-related decline was found in CR animals. Thus, our results showed that CR preserves aerobic function in aged skeletal muscles by facilitating a higher in situ function of complex IV and by preventing the age-related decline in mitochondrial oxidative capacity.