[Background] Sarcopenia is characterized by loss of skeletal muscle function and mass associated with aging. Autophagy is positively regulated by an NAD⁺-dependent protein deacetylase SIRT1 and has been reported to maintain skeletal muscle. In this study, we examined the effect of an activator of SIRT1, resveratrol (RSV), on muscle autophagy and age-related sarcopenia.
[Method and Results] Ddy mice were fed a normal diet or a diet containing RSV (0.4 g/kg diet) for 37 weeks starting at 23 weeks of age. Although rotarod running time gradually shortened with aging in both groups, it was longer in the RSV-fed group at 50 weeks of age. At 60 weeks of age, we sampled tibialis anterior muscles for further analyses in control mice (60 wo) and RSV-treated mice (60 wo+RSV). Compared with mice at 20 weeks of age (20 wo), myofiber diameter determined by HE staining was reduced in 60 wo; however, it was maintained in 60 wo+RSV. Western blot analysis using anti-acetyl-lysine antibody showed increases in acetylated proteins in 60 wo compared to 20 wo, suggesting suppression of SIRT1 activity in 60 wo. However, RSV blocked the aging-induced protein acetylation. LC-II/LC3-I ratio, a marker of autophagic activity, was lower and protein level of p62, which degraded by autophagy, was higher in 60 wo than those in 20 wo, suggesting aging-associated suppression of autophagy. These aging-associated changes were attenuated by RSV treatment.
[Conclusion] These results suggest that activation of SIRT1 in skeletal muscle preserves autophagic activity and attenuates age-related sarcopenia.