State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Cell Prolif. 2023 May;56(5):e13455. doi: 10.1111/cpr.13455. Epub 2023 May 17.
Sarcopenia, a skeletal muscle disorder in which loss of muscle mass and function progresses with age, is associated with increased overall frailty, risk of falling and mortality in the elders. Here, we reveal that SESN1 safeguards skeletal muscle from ageing downstream of the longevity gene FOXO3, which we recently reported is a geroprotector in primate skeletal muscle. Knockdown of SESN1 mimicked the human myotube ageing phenotypes observed in the FOXO3-deficient human myotubes, whereas genetic activation of SESN1 alleviated human myotube senescence. Of note, SESN1 was identified as a protective secretory factor against muscle atrophy. Administration of recombinant SESN1 protein attenuated senescence of human myotubes in vitro and facilitated muscle regeneration in vivo. Altogether, we unveil a key role of SESN1 downstream of FOXO3 in protecting skeletal muscle from ageing, providing diagnostic biomarkers and intervention strategies for counteracting skeletal muscle ageing and related diseases.
肌肉减少症是一种随着年龄增长而导致肌肉质量和功能逐渐丧失的骨骼肌肉疾病，与老年人整体虚弱、易跌倒和死亡风险增加有关。在这里，我们揭示 SESN1 可以保护骨骼肌免受长寿基因 FOXO3 的衰老影响，我们最近报道称 FOXO3 是灵长类骨骼肌的一种抗衰老保护剂。SESN1 的敲低模拟了在 FOXO3 缺陷的人类肌管中观察到的人类肌管衰老表型，而 SESN1 的遗传激活则缓解了人类肌管衰老。值得注意的是，SESN1 被鉴定为一种针对肌肉萎缩的保护性分泌因子。重组 SESN1 蛋白的给药可减轻体外人类肌管的衰老，并促进体内肌肉再生。总的来说，我们揭示了 SESN1 在保护骨骼肌免受衰老方面的关键作用，为对抗骨骼肌衰老和相关疾病提供了诊断生物标志物和干预策略。
