The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23‐25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response to injury in comparison to young (2‐3 months old) mice. Knockdown of ARNT in a primary muscle cell line impaired differentiation in vitro. Skeletal muscle‐specific ARNT deletion in young mice resulted in decreased levels of whole muscle N1ICD and limited muscle regeneration. Administration of a systemic hypoxia pathway activator (ML228), which simulates the actions of ARNT, rescued skeletal muscle regeneration in both old and ARNT‐deleted mice. These results suggest that the loss of ARNT in skeletal muscle is partially responsible for diminished myogenic potential in aging and activation of hypoxia signaling holds promise for rescuing regenerative activity in old muscle.

中文翻译：

---

骨骼肌中 ARNT 的丧失限制了衰老过程中的肌肉再生

随着年龄的增长，骨骼肌的再生能力显着下降。芳烃受体核转位子 (ARNT) 是缺氧信号通路的关键组成部分，在年老（23-25 个月大）小鼠的骨骼肌中表达较少。与年轻（2-3 个月大）小鼠相比，这种 ARNT 缺失与 Notch1 细胞内结构域 (N1ICD) 水平降低和损伤再生反应受损有关。在原代肌肉细胞系中敲除 ARNT 会损害体外分化。年轻小鼠骨骼肌特异性 ARNT 缺失导致全肌肉 N1ICD 水平降低和肌肉再生受限。系统性缺氧通路激活剂 (ML228) 的给药模拟 ARNT 的作用，在年老和 ARNT 缺失的小鼠中拯救了骨骼肌再生。