Nature2014-06-26 1:12 PM

“卫星细胞”与肌肉衰老 Geriatric muscle stem cells switch reversible quiescence into senescence

论文摘要 

对成年哺乳动物干细胞的功能来说至关重要的特性之一是,长时间保持静止状态的能力以及需要再生时做出反应的能力。骨骼肌数量及功能的损失是人类晚年衰老的共同特征,与被称为“卫星细胞”的骨骼肌干细胞的再生能力的丧失有关。Pura Muñoz-Cánoves及同事发现,衰老中的“卫星细胞”发生从静止状态向衰老前状态的不可逆转变,这与已被发现是衰老的一个标志的肿瘤抑制蛋白p16INK4a的表达水平增加有关。成年期间p16INK4a的抑制被发现能将“卫星细胞”保持在一个可逆的静止状态,使肌肉能够再生;p16INK4a在老年人的“卫星细胞”中失调,肌肉再生潜力丧失。

Abstract 

Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with ageing. Here we report that geriatric satellite cells are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and that this irreversibly affects their intrinsic regenerative and self-renewal capacities. In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16INK4a (also called Cdkn2a). On injury, these cells fail to activate and expand, undergoing accelerated entry into a full senescence state (geroconversion), even in a youthful environment. p16INK4a silencing in geriatric satellite cells restores quiescence and muscle regenerative functions. Our results demonstrate that maintenance of quiescence in adult life depends on the active repression of senescence pathways. As p16INK4a is dysregulated in human geriatric satellite cells, these findings provide the basis for stem-cell rejuvenation in sarcopenic muscles.

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