Brown adipose tissue(BAT),crucial for mammalian thermoregulation and energy metabolism,boasts a dense concentration of mitochondria.As a vital cellular organelle,mitochondria undergo substantial remodeling in cold env...Brown adipose tissue(BAT),crucial for mammalian thermoregulation and energy metabolism,boasts a dense concentration of mitochondria.As a vital cellular organelle,mitochondria undergo substantial remodeling in cold environments,playing a pivotal role in maintaining body temperature and energy balance[1].Mitochondrial dynamics.展开更多
The prevalence of cardiovascular diseases(CVDs)has increased markedly as the world population has aged.Long non-coding RNAs(lncRNAs)have been reported as novel regulators in diverse pathophysiological conditions.Here,...The prevalence of cardiovascular diseases(CVDs)has increased markedly as the world population has aged.Long non-coding RNAs(lncRNAs)have been reported as novel regulators in diverse pathophysiological conditions.Here,we performed RNA sequencing(RNA-seq)and observed that the lncRNA Zeb1os1(zinc finger E-box binding homeobox 1,opposite strand 1),which is known as ZEB1-AS1(zinc finger E-box binding homeobox 1 antisense 1)in humans,was upregulated in the aged mice hearts,senescent cardiomyocytes,and human blood from elderly individuals.The human blood ZEB1-AS1 level was positively relevant to human age but negatively relevant to peak E to peak A(E/A).Silencing Zeb1os1 ameliorated diastolic dysfunction and cardiac senescence in aged mice.On the other hand,Zeb1os1 overexpression triggered cardiac dysfunction resembling that observed in aged mice.Mechanistically,we provide compelling evidence that Zeb1os1 interacts with the transient receptor potential mucolipin 1(TRPML1)for ubiquitination(UB)-mediated degradation.This process inhibits lysosomal Ca^(2+)efflux,impairing lysosome function.In addition,the functional domain of Zeb1os1,which contains the key nucleotides responsible for the pro-senescence property of full-length Zeb1os1 in cardiomyocytes.Together,these data suggest that Zeb1os1 is a potential target for ameliorating lysosomal dysfunction and aging-related cardiac impairment.展开更多
基金This study was financially supported by the National Natural Science Foundation of China(No.82270396).
文摘Brown adipose tissue(BAT),crucial for mammalian thermoregulation and energy metabolism,boasts a dense concentration of mitochondria.As a vital cellular organelle,mitochondria undergo substantial remodeling in cold environments,playing a pivotal role in maintaining body temperature and energy balance[1].Mitochondrial dynamics.
基金funded by the National Natural Science Foundation of China(82273919,82270396,and U21A20339)the China Postdoctoral Science Foundation(2023T160176)。
文摘The prevalence of cardiovascular diseases(CVDs)has increased markedly as the world population has aged.Long non-coding RNAs(lncRNAs)have been reported as novel regulators in diverse pathophysiological conditions.Here,we performed RNA sequencing(RNA-seq)and observed that the lncRNA Zeb1os1(zinc finger E-box binding homeobox 1,opposite strand 1),which is known as ZEB1-AS1(zinc finger E-box binding homeobox 1 antisense 1)in humans,was upregulated in the aged mice hearts,senescent cardiomyocytes,and human blood from elderly individuals.The human blood ZEB1-AS1 level was positively relevant to human age but negatively relevant to peak E to peak A(E/A).Silencing Zeb1os1 ameliorated diastolic dysfunction and cardiac senescence in aged mice.On the other hand,Zeb1os1 overexpression triggered cardiac dysfunction resembling that observed in aged mice.Mechanistically,we provide compelling evidence that Zeb1os1 interacts with the transient receptor potential mucolipin 1(TRPML1)for ubiquitination(UB)-mediated degradation.This process inhibits lysosomal Ca^(2+)efflux,impairing lysosome function.In addition,the functional domain of Zeb1os1,which contains the key nucleotides responsible for the pro-senescence property of full-length Zeb1os1 in cardiomyocytes.Together,these data suggest that Zeb1os1 is a potential target for ameliorating lysosomal dysfunction and aging-related cardiac impairment.
