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
This study applied in vivo and in vitro methods to investigate the effect of dietary N-carbamoylglutamate(NCG)on lipid metabolism,inflammation and apoptosis related-gene expression in visceral adipose tissue and isola...This study applied in vivo and in vitro methods to investigate the effect of dietary N-carbamoylglutamate(NCG)on lipid metabolism,inflammation and apoptosis related-gene expression in visceral adipose tissue and isolated adipocytes of Japanese seabass(Lateolabrax japonicus).A basal diet and a test diet supplemented with 720 mg/kg NCG were fed to the fish for 10 weeks.During the growth trial,no mortality and no significant differences in growth performance were observed in fish between the 2 groups(P>0.05).Plasma Arg content and mRNA level of argininosuccinate synthetase(ASS)in adipose tissue were significantly increased,which indicated that NCG inclusion promoted endogenous Arg synthesis.Thereafter,the potential effects of NCG treatment on lipid metabolism-related genes expression were studied through in vivo and in vitro methods.In the present study,we successfully established a primary adipocytes culture system and isolated pre-adipocytes in vitro of Japanese seabass for the first time.Both the results in vivo and in vitro showed that NCG treatment decreased the mRNA levels of genes related to adipogenesis(fatty acid synthase,FASN),cholesterol synthesis(3-hydroxy-3-methylglutaryl-CoA reductase,HMGCR)and fat deposition(lipoprotein lipase[LPL]and leptin),which revealed the underlying mechanism of NCG on reducing fat deposition.The results of this study demonstrated that NCG inclusion reduced the expression of inflammatory and apoptosis cytokines markedly in vivo and in vitro.In conclusion,NCG did exert beneficial effects on ameliorating adipo-genesis,inflammation and apoptosis via promoting Arg endogenous synthesis in Japanese seabass.展开更多
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.
基金supported by the National Key R&D Program of China(2019YFD0900200,2018YFD0900400)the Agricultural Science and Technology Innovation Program(CAAS-ASTIP-2017-FRI-08)+2 种基金Beijing Technology System for Sturgeon and Salmonids(BAIC08-2021)National Natural Science Foundation of China(31902382)Natural Science Foundation of Beijing(6204047)
文摘This study applied in vivo and in vitro methods to investigate the effect of dietary N-carbamoylglutamate(NCG)on lipid metabolism,inflammation and apoptosis related-gene expression in visceral adipose tissue and isolated adipocytes of Japanese seabass(Lateolabrax japonicus).A basal diet and a test diet supplemented with 720 mg/kg NCG were fed to the fish for 10 weeks.During the growth trial,no mortality and no significant differences in growth performance were observed in fish between the 2 groups(P>0.05).Plasma Arg content and mRNA level of argininosuccinate synthetase(ASS)in adipose tissue were significantly increased,which indicated that NCG inclusion promoted endogenous Arg synthesis.Thereafter,the potential effects of NCG treatment on lipid metabolism-related genes expression were studied through in vivo and in vitro methods.In the present study,we successfully established a primary adipocytes culture system and isolated pre-adipocytes in vitro of Japanese seabass for the first time.Both the results in vivo and in vitro showed that NCG treatment decreased the mRNA levels of genes related to adipogenesis(fatty acid synthase,FASN),cholesterol synthesis(3-hydroxy-3-methylglutaryl-CoA reductase,HMGCR)and fat deposition(lipoprotein lipase[LPL]and leptin),which revealed the underlying mechanism of NCG on reducing fat deposition.The results of this study demonstrated that NCG inclusion reduced the expression of inflammatory and apoptosis cytokines markedly in vivo and in vitro.In conclusion,NCG did exert beneficial effects on ameliorating adipo-genesis,inflammation and apoptosis via promoting Arg endogenous synthesis in Japanese seabass.
