Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1
Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1
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DOI：
10.1038/s42255-020-0190-0
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发表时间：
2020-04-01
影响因子：
20.8
通讯作者：
Rando, Thomas A.
中科院分区：
文献类型：
--
作者：
Brett, Jamie O.;Arjona, Marina;Rando, Thomas A.
老化损害组织修复。这种缺陷在骨骼肌中很明显，肌肉干细胞（MuSC）的再生在成年动物中很强大，但在老年生物体中效率低下。尽管有这种功能下降，但通过改善系统环境的策略，如异时共生，老年MuSC可以恢复活力。其中一个策略，运动，长期以来一直被认为对健康有益，但它对组织再生背景下衰老干细胞功能的影响尚未完全了解。在这里，我们表明，自愿轮跑形式的运动加速了老年小鼠的肌肉修复，并改善了老年MuSC功能。通过转录谱分析和遗传学研究，我们发现旧MuSC激活能力的恢复取决于Cyclin D1的恢复，其表达在MuSC中随年龄的增长而下降。药理学研究表明，细胞周期蛋白D1通过抑制TGF-β信号传导维持MuSC活化能力。总之，这些研究表明，自愿运动是一个可行的干预老年MuSC振兴。此外，这项工作突出了细胞周期蛋白D1在干细胞静止中的独特作用。
Ageing impairs tissue repair. This defect is pronounced in skeletal muscle, whose regeneration by muscle stem cells (MuSCs) is robust in young-adult animals, but inefficient in older organisms. Despite this functional decline, old MuSCs are amenable to rejuvenation through strategies that improve the systemic milieu, such as heterochronic parabiosis. One such strategy, exercise, has long been appreciated for its benefits on healthspan, but its effects on aged stem-cell function in the context of tissue regeneration are incompletely understood. Here, we show that exercise in the form of voluntary wheel running accelerates muscle repair in old mice and improves old MuSC function. Through transcriptional profiling and genetic studies, we discovered that the restoration of old MuSC activation ability hinges on restoration of Cyclin D1, whose expression declines with age in MuSCs. Pharmacologic studies revealed that Cyclin D1 maintains MuSC activation capacity by repressing TGF-beta signalling. Taken together, these studies demonstrate that voluntary exercise is a practicable intervention for old MuSC rejuvenation. Furthermore, this work highlights the distinct role of Cyclin D1 in stem-cell quiescence.