Department of Anatomy and Histology, School of Basic Medical Science, Tianjin Medical University, China.
Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, China.
J Gerontol A Biol Sci Med Sci. 2021 Jun 14;76(7):1161-1168. doi: 10.1093/gerona/glab029.
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 α2 (AMPKα2). This study indicates that aerobic exercise alleviates the negative effects resulting from sarcopenia via the Sesn2/AMPKα2 pathway and provides new insights into the molecular mechanism by which the Sesn2/AMPKα2 signaling axis mediates the beneficial impact of exercise on sarcopenia.
肌肉减少症是与年龄相关的骨骼肌质量和功能丧失，它导致老年人群的高发病率和死亡率。为了避免肌肉减少症的发生和进展，有必要进行规律的运动，而其潜在的分子机制尚不清楚。我们的数据显示，肌肉减少症引起的结果，包括肌肉质量和力量的丧失、比目鱼肌纤维横截面积的减少、慢性炎症和功能失调的线粒体增加，都可以通过调节运动得到逆转。Sesn2（Sestrin2）的敲除或沉默导致体内和体外的线粒体融合和裂变、线粒体生物发生和自噬损伤失衡，而有氧运动或 Sesn2 的过表达可以减轻这种损伤。此外，我们发现 Sesn2 对线粒体功能的影响依赖于 AMP 激活的蛋白激酶α2（AMPKα2）。这项研究表明，有氧运动通过 Sesn2/AMPKα2 途径减轻了肌肉减少症的负面影响，并为 Sesn2/AMPKα2 信号轴介导运动对肌肉减少症的有益影响的分子机制提供了新的见解。
