Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory disease.However,a systematic characterization and comprehensive understandi...Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory disease.However,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking.Here,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were elucidated.Epithelial cells were identified as the most affected cell types by aging in the gingiva.Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal cells.The decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects.Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.展开更多
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 o...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.展开更多
文摘Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis,a worldwide prevalent inflammatory disease.However,a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking.Here,we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging,by which a panel of cell type-specific signatures were elucidated.Epithelial cells were identified as the most affected cell types by aging in the gingiva.Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis,which declined during aging in epithelial cells,especially in basal cells.The decline of YAP activity during aging was confrmed in the human gingival tissues,and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects.Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases,with the ultimate goal of advancing periodontal health and promoting healthy aging.
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)+10 种基金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).
文摘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.
