Aerobic Exercise Improves Mitochondrial Function in Sarcopenia Mice Through Sestrin2 in an AMPKα2-Dependent Manner

Sarcopenia, the age-related loss of skeletal muscle mass and function, contributes to high morbidity and mortality in the older population. Regular exercise is necessary to avoid the initiation and progression of sarcopenia, in which the underlying molecular mechanism is still not clear. Our data revealed that the outcomes induced by sarcopenia, including muscle mass and strength loss, decreased cross-sectional area of gastrocnemius fiber, chronic inflammation, and increased dysfunctional mitochondria, were reversed by regulation exercise. Knockout or silencing of Sestrin2 (Sesn2) resulted in imbalanced mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy damage in vivo and in vitro, which was attenuated by aerobic exercise or overexpression of Sesn2. Moreover, we found that the effects of Sesn2 on mitochondrial function are dependent on AMP-activated protein kinase alpha 2 (AMPK alpha 2). This study indicates that aerobic exercise alleviates the negative effects resulting from sarcopenia via the Sesn2/AMPK alpha 2 pathway and provides new insights into the molecular mechanism by which the Sesn2/AMPK alpha 2 signaling axis mediates the beneficial impact of exercise on sarcopenia.

Automated summary

Regular exercise can reverse the negative effects of sarcopenia on muscle mass and function, by regulating the Sesn2/AMPK alpha 2 pathway. This study provides new insights into the molecular mechanism by which exercise alleviates the consequences of sarcopenia.