[Background and Aim] SIRT1, an NAD+-dependent protein deacetylase, exerts cytoprotective effects. We previously reported that resveratrol, an activator of SIRT1, attenuates skeletal muscle pathology in a mouse model of Duchenne muscular dystrophy. The purpose of this study was to elucidate the function of SIRT1 in skeletal muscle using muscle-specific SIRT1 knockout mice (SIRT1MKO).
[Method and Result] Treadmill running distance and inverted net hanging time were significantly shorter in SIRT1MKO than those in wild-type mouse (WT). Blood level of creatine kinase, a marker of muscle membrane injury, after treadmill exercise was significantly higher in SIRT1MKO (2201 ± 407 U/L) than WT (481 ± 99 U/L). Furthermore, Evans blue uptake into muscle cells, which reflects plasma membrane rupture, after treadmill was increased in SIRTMKO than that in WT (1.8% vs. 0.5%, P<0.05). Histological analyses of quadriceps muscle showed that central nuclei, an indicator of muscle regeneration, and atrophied muscle fibers with (<1,500 μm2) were significantly increased in SIRT1MKO compared to those in WT.
[Conclusion] These results suggest that SIRT1 maintains muscle function and attenuates muscle membrane injury.