p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice.
p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice.
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骨骼肌老化导致骨骼肌质量逐渐减少，骨骼肌功能下降，再生能力下降，从而导致肌肉减少症和死亡率增加。虽然肌肉减少症的机制尚不清楚，但骨骼肌干细胞或卫星细胞是肌肉再生所必需的。因此，识别衰老过程中影响卫星细胞功能的信号通路可能为对抗肌肉减少症的治疗靶点提供见解。在这里，我们发现在衰老的卫星细胞中，通过FGF受体1和p38αβ MAPK信号的改变，细胞自我更新的自主丧失发生。我们进一步证明这些途径的药理学操作可以改善与年龄相关的自我更新缺陷。因此，我们的数据强调了与年龄相关的卫星细胞稳态网络的解除管制，并揭示了治疗进行性肌肉萎缩的潜在治疗机会。
Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and decreased regenerative capacity, which can lead to sarcopenia and increased mortality. While the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Therefore, identification of signaling pathways affecting satellite cell function during aging may provide insights into therapeutic targets for combating sarcopenia. Here, we show that a cell-autonomous loss in self-renewal occurs via alterations in FGF Receptor 1 and p38αβ MAPK signaling in aged satellite cells. We further demonstrate that pharmacological manipulation of these pathways can ameliorate age-associated self-renewal defects. Thus, our data highlight an age-associated deregulation of a satellite cell homeostatic network and reveal potential therapeutic opportunities for the treatment of progressive muscle wasting.
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影响因子：
2.7
作者：
Day, Kenneth;Shefer, Gabi;Yablonka-Reuveni, Zipora
通讯作者：
Yablonka-Reuveni, Zipora
影响因子：
4.6
作者：
Lepper, Christoph;Partridge, Terence A.;Fan, Chen-Ming
通讯作者：
Fan, Chen-Ming
影响因子：
5.2
作者：
Collins, Charlotte A.;Zammit, Peter S.;Partridge, Terence A.
通讯作者：
Partridge, Terence A.
影响因子：
6.7
作者：
Landi, Francesco;Cruz-Jentoft, Alfonso J.;Onder, Graziano
通讯作者：
Onder, Graziano
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA