SIRT1, an NAD+-dependent deacetylase, positively regulates autophagy, which maintains muscle function and declines with age. We recently reported that administration of resveratrol (RSV), an activator of SIRT1, to a mouse model of Duchenne muscular dystrophy restores muscle autophagy, preserves muscle mass, and improves exercise tolerance. Here, we hypothesized that RSV attenuates age-related loss of muscle mass and preserves muscle function by activating autophagy.
We compared exercise tolerance of aged DDY mice that had either a control diet or a diet containing RSV for 37 weeks. Although treadmill running distance and grip strength of the mouse were not changed, rotarod riding time was significantly extended in RSV-treated mouse. Myofiber diameter of tibialis anterior muscle was higher in RSV-treated mice. In the muscle of RSV-treated mice, acetylated lysine levels were reduced, suggesting that SIRT1 is activated by administration of RSV. In addition, RSV increased LC3-II protein level, a marker of autophagosomes, and decreased levels of p62 and ubiquitinated proteins, which are degraded by autophagy. These results suggest that RSV activates autophagy in the muscle.
In conclusion, we propose that RSV attenuates aging-related loss of muscle mass and motor dysfunction via activating autophagy in mice.