Myostatin Exhibits an Evolutionarily Conserved Circadian Pattern in Skeletal Muscles

作者：Xiangpeng Liu, Changyou Song, Yan Xiong, Jinxin Gu, Lianxin Wu, Taole Liu, Xiyue Chen, Hui‐Kuo G. Shu, Yingying Dong, Tizhong Shan, Sheng Wang, Yucheng Zhu, Tongxing Song, Lei Fu, Lin Yaqiu, Can Liu, Ruiqi Zheng, Xiao Zhao, Hongxia Li, Yong Xu, Shihuan Kuang, Han Wang, Bin Guo, Pao Xu, Zhihao Jia · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2025 · DOI：10.1002/jcsm.70130 · 被引用次数：3 · 研究领域：Muscle Physiology and Disorders、Circadian rhythm and melatonin、Genetics, Aging, and Longevity in Model Organisms

ABSTRACT Introduction Myostatin (MSTN), a transforming growth factor‐beta (TGF‐β) superfamily member, is an evolutionarily conserved negative regulator of skeletal muscle mass. Loss of MSTN commonly promotes augmentation in skeletal muscle mass in all animal species examined. Recent studies have demonstrated that circadian clock proteins play a critical role in the regulation of muscle mass and function, in part by modulating the expression of key muscle‐related genes. While myostatin has an important role in sustaining skeletal muscle protein turnover, it is unknown if circadian clock proteins regulate myostatin in a circadian pattern. Methods We analysed time‐course muscle samples from 16 animal species ranging from Caenorhabditis elegans to humans and examined the rhythmic expression pattern of Mstn . We also used various circadian clock deficient models such as muscle‐specific Bmal1 knockout, Per1/Per2 double knockout, genetic knockout of per0 and tim0 genes in fruit flies, clocka gene in zebrafish and environmental perturbation. Results Both mRNA and protein of MSTN exhibit rhythmic expression patterns in a variety of animal species ranging from Caenorhabditis elegans ( C. elegans ) to humans. The rhythmicity of Mstn orthologs in muscle is evolutionarily conserved along with their sequence evolution in C. elegans , Drosophila melanogaster , Crustacea , fish and mammals including mice (mRNA: amplitude = 0.188, p < 0.0001; protein: amplitude = 0.255, p < 0.05), goats...