Exercise has long been known to extend health and lifespan in humans and other mammals. However, typically exercise is thought to slow the loss of function that accompanies aging. Brett et al. have now shown that exercise restores functional competency to regenerate muscle stem cells (MuSCs) in mice as well as restore a significant portion of the transcriptional signature associated with young MuSCs. The mechanism involves the likely induction of plasma-borne factors that upregulate cell cycle regulator cyclin D1, which otherwise decreases with increasing age. Cyclin D1, in turn, through its noncanonical attenuation of TGF-beta/Smad3 signaling, helps maintain the regenerative capacity of MuSCs, which is lost as TGF-beta signaling increases with age. Interestingly, elevated levels of some proinflammatory regulators including NF-κB, TNF-alpha, and interleukin 6 (IL-6) are also reduced by exercise or ectopic expression of cyclin D1. Importantly, the rejuvenation is not complete, as Notch signaling, which also decreases with age, remains at old levels and the rejuvenative effect is not permanent: wearing off in ∼2 weeks after cessation of exercise. Understanding the limitations of the rejuvenative effect of exercise on MuSCs at the molecular level, including changes in the epigenome such as altered DNA methylation age, will be critical in developing more significant rejuvenative therapies including some for aged people wherein morbidities limit exercise.

中文翻译：

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运动可以部分恢复肌肉干细胞的活力。

长期以来，锻炼可以延长人类和其他哺乳动物的健康和寿命。然而，通常认为运动会延缓衰老带来的功能丧失。Brett等。现已显示，锻炼可恢复小鼠再生肌肉干细胞（MuSCs）的功能能力，并恢复与年轻MuSCs相关的大部分转录特征。该机制涉及可能诱导血浆上调因子，这些因子上调细胞周期调节因子cyclin D1，否则随着年龄的增长而降低。反过来，细胞周期蛋白D1通过其非典型的TGF-β/ Smad3信号传导衰减，有助于维持MuSC的再生能力，随着TGF-β信号随着年龄的增长而增加，MuSC的再生能力就会丧失。有趣的是，某些促炎性调节剂（包括NF-κB，TNF-α，运动和异位表达细胞周期蛋白D1也会降低白细胞介素6（IL-6）和白介素6（IL-6）的表达。重要的是，恢复还没有完成，因为随着年龄的增长，Notch信号也会随着年龄的增长而降低，并且恢复作用不是永久的：在运动停止后约2周内逐渐消失。在分子水平上了解运动对MuSCs的恢复作用的局限性，包括表观基因组的改变（例如DNA甲基化年龄的改变），对于开发更重要的恢复性疗法（包括针对某些发病率限制锻炼的老年人）至关重要。仍然保持旧水平，并且恢复效果不是永久的：运动停止后约2周内逐渐消失。在分子水平上了解运动对MuSCs的恢复作用的局限性，包括表观基因组的变化（例如DNA甲基化年龄的改变），对于开发更重要的恢复性疗法（包括针对某些发病率限制运动的老年人）至关重要。仍然保持旧水平，并且恢复作用不是永久的：运动停止后约2周内逐渐消失。在分子水平上了解运动对MuSCs的恢复作用的局限性，包括表观基因组的改变（例如DNA甲基化年龄的改变），对于开发更重要的恢复性疗法（包括针对某些发病率限制锻炼的老年人）至关重要。