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Single-nucleus profiling unveils a geroprotective role of the Foxo3 in primate skeletal muscle aging

Protein & Cell 2023年第7期14卷 499-514页

作者： 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 State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China China National Center for Bioinformation Beijing 100101China Aging Translational Medicine Center Intemational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China The Key Laboratory of Geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China Clinical Stem Cell Research Center Peking University Third HospitalBeijing 100191China Department of Orthopaedics Peking University First HospitalBeijing 100034China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Altos labs Inc.San DiegoCA 94022USA The Fifth People's Hospital of Chongqing Chongqing 400062China

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia,and increases the risk of many aging-related metabolic ***,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 *** found a downregulation of Foxo3 in aged primate skeletal muscle,and identi-fied FOxo3 as a hub transcription factor maintaining skeletal muscle *** the 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 ***,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 the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-relateddisorders.

关键词： single-nucleus RNA sequencing primate aging skeletal muscle FOxO3

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