Autophagy maintains stemness by preventing senescence
Autophagy maintains stemness by preventing senescence
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DOI：
10.1038/nature16187
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发表时间：
2016-01-07
期刊：
影响因子：
64.8
通讯作者：
Munoz-Canoves, Pura
中科院分区：
文献类型：
--
作者：
Garcia-Prat, Laura;Martinez-Vicente, Marta;Munoz-Canoves, Pura
在衰老过程中，肌肉干细胞的再生功能下降。在老年晚期，由于从正常的静止状态过渡到不可逆的衰老状态，这种下降是最大的。卫星细胞是如何保持静止状态并避免衰老的，直到老年仍然是未知的。在这里，我们报告说，基础自噬是必不可少的，以维持小鼠干细胞的静止状态。生理老化的卫星细胞中自噬的失败或年轻细胞中自噬的遗传损伤通过蛋白质稳态的丧失、增加的线粒体功能障碍和氧化应激导致进入衰老，从而导致卫星细胞的功能和数量下降。自噬的重建逆转衰老并恢复老年卫星细胞的再生功能。由于自噬在人类老年卫星细胞中也有所下降，我们的研究结果揭示自噬是一种决定性的干细胞命运调节剂，对促进肌肉减少症的肌肉再生具有重要意义。
During ageing, muscle stem-cell regenerative function declines. At advanced geriatric age, this decline is maximal owing to transition from a normal quiescence into an irreversible senescence state. How satellite cells maintain quiescence and avoid senescence until advanced age remains unknown. Here we report that basal autophagy is essential to maintain the stem-cell quiescent state in mice. Failure of autophagy in physiologically aged satellite cells or genetic impairment of autophagy in young cells causes entry into senescence by loss of proteostasis, increased mitochondrial dysfunction and oxidative stress, resulting in a decline in the function and number of satellite cells. Re-establishment of autophagy reverses senescence and restores regenerative functions in geriatric satellite cells. As autophagy also declines in human geriatric satellite cells, our findings reveal autophagy to be a decisive stem-cell-fate regulator, with implications for fostering muscle regeneration in sarcopenia.