各种肌肉疾病之间的共同点是肌肉质量、功能和再生的丧失，这严重限制了活动能力并损害了生活质量。由于肌肉干细胞（MuSC）在促进肌肉修复中发挥着关键作用，靶向肌肉再生调节剂已被证明是一种有前途的肌肉修复治疗方法。然而，驱动肌肉再生的潜在分子机制很复杂且知之甚少。在这里，我们发现了一种新的肌肉再生调节因子，Deaf1（变形表皮自动调节因子-1）——foxo 信号下游的转录因子。我们发现 Deaf1 受到 FOXO 的转录抑制，并且 DEAF1 靶向 Pik3c3 和 Atg16l1 启动子区域并抑制其表达。因此，Deaf1 缺失会诱导巨自噬/自噬，进而阻碍 MuSC 的存活和分化。相比之下，Deaf1 过度表达会使 MuSC 中的自噬失活，导致蛋白质聚集增加和细胞死亡。 Deaf1 缺失及其过度表达都会导致肌肉再生缺陷，这一事实凸显了在肌肉再生过程中微调 DEAF1 调节的自噬的重要性。我们进一步表明 Deaf1 表达在衰老和恶病质 MuSC 中发生改变。操纵Deaf1表达可以减轻老年小鼠或患有恶病质癌症的小鼠的肌肉萎缩并恢复肌肉再生。总之，我们的研究结果揭示了 DEAF1 在肌肉再生中的进化保守作用，为开发针对肌肉萎缩的新治疗策略提供了见解。

The commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we identified a new regulator of muscle regeneration, Deaf1 (Deformed epidermal autoregulatory factor-1) - a transcriptional factor downstream of foxo signaling. We showed that Deaf1 is transcriptionally repressed by FOXOs and that DEAF1 targets to Pik3c3 and Atg16l1 promoter regions and suppresses their expression. Deaf1 depletion therefore induces macroautophagy/autophagy, which in turn blocks MuSC survival and differentiation. In contrast, Deaf1 overexpression inactivates autophagy in MuSCs, leading to increased protein aggregation and cell death. The fact that Deaf1 depletion and its overexpression both lead to defects in muscle regeneration highlights the importance of fine tuning DEAF1-regulated autophagy during muscle regeneration. We further showed that Deaf1 expression is altered in aging and cachectic MuSCs. Manipulation of Deaf1 expression can attenuate muscle atrophy and restore muscle regeneration in aged mice or mice with cachectic cancers. Together, our findings unveil an evolutionarily conserved role for DEAF1 in muscle regeneration, providing insights into the development of new therapeutic strategies against muscle atrophy.