Single-nucleus profiling unveils a geroprotective role of the Foxo3 in primate skeletal muscle aging
作者机构：State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China University of Chinese Academy of SciencesBeijing 100049China Institute for Stem Cell and RegenerationChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision MedicineBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China China National Center for BioinformationBeijing 100101China Aging Translational Medicine CenterIntemational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijing 100191China The Key Laboratory of GeriatricsBeijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China Clinical Stem Cell Research CenterPeking University Third HospitalBeijing 100191China Department of OrthopaedicsPeking University First HospitalBeijing 100034China Sino-Danish CollegeUniversity of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and ResearchBeijing 101408China Altos LabsInc.San DiegoCA 94022USA The Fifth People's Hospital of ChongqingChongqing 400062China
出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)
年 卷 期：2023年第14卷第7期
页 面：499-514页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 10[医学]
基 金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16000000) the National Natural Science Foundation of China(Nos.82071588,81921006,82125011,92149301,92168201,92049116,32121001,82192863,91949209,92049304,82122024,82001477,31900523,81861168034,32000500,82271600,82201714) the National Key Research and Development Program of China(Nos.2018YFC2000100,2020YFA0804000,2018YFA0107203,2020YFA0112200,2021YFF1201005,2021ZD0202401,2018YFC2000400,2020YFA0113400,2021YFE0111800,2022YFA1103700) the Program of the Beijing Natural Science Foundation(No.Z190019) K.C.Wong Education Foundation(Nos.GJTD-2019-06,GJTD-2019-08) Beijing Medical Research(2021-8) the Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(No.11000022T000000461062) Young Elite Scientists Sponsorship Program by CAST(Nos.YESS20200012,YESS20210002) CAS Project for Young Scientists in Basic Research(No.YSBR-076,YSBR-012,YSBR-036) Youth Innovation Promotion Association of CAS(Nos.E1CAZW0401,2020085,2022083) the Informatization Plan of Chinese Academy of Sciences(Nos.CAS-WX2022SDC-XK14,CASWX2021SF-0301,CAS-WX2021SF-0101) the Tencent Foundation(No.2021-1045),CAMS Innovation Fund for Medical Sciences(No.2021-12M-1-050) the Fellowship of China Postdoctoral Science Foundation(2022M712216).
主 题：single-nucleus RNA sequencing primate aging skeletal muscle FOxO3
摘 要：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 identi-fied FOxo3 as a hub transcription factor maintaining skeletal muscle homeostasis.Through 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 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 the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-relateddisorders.
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