Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging

Autor: Ying Jing, Yuesheng Zuo, Yang Yu, Liang Sun, Zhengrong Yu, Shuai Ma, Qian Zhao, Guoqiang Sun, Huifang Hu, Jingyi Li, Daoyuan Huang, Lixiao Liu, Jiaming Li, Zijuan Xin, Haoyan Huang, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Si Wang, Jing Qu, Guang-Hui Liu
Rok vydání: 2022
Předmět:
Zdroj: Protein & Cell.
ISSN: 1674-8018
1674-800X
DOI: 10.1093/procel/pwac061
Popis: Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Databáze: OpenAIRE
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