Decades of investigation on DNA methylation have led to deeper insights into its metabolic mechanisms and biological functions.This understanding was fueled by the recent development of genome editing tools and our im...Decades of investigation on DNA methylation have led to deeper insights into its metabolic mechanisms and biological functions.This understanding was fueled by the recent development of genome editing tools and our improved capacity for analyzing the global DNA methylome in mammalian cells.This review focuses on the maintenance of DNA methylation patterns during mitotic cell division.We discuss the latest discoveries of the mechanisms for the inheritance of DNA methylation as a stable epigenetic memory.We also highlight recent evidence showing the rapid turnover of DNA methylation as a dynamic gene regulatory mechanism.A body of work has shown that altered DNA methylomes are common features in aging and disease.We discuss the potential links between methylation maintenance mechanisms and diseaseassociated methylation changes.展开更多
Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into ...Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into distinct and specialized cells.As stem cells age,their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired.From a molecular perspective,these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration(i.e epigenomic profile)as well as changes in the tissue microenviroment,both into the niche and by systemic circulating factors.Strikingly,it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various agingassociated disorders.Therefore,understanding how resident stem cell age and affects near and distant tissues is fundamental.Here,we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number,function and phenotype that determine the loss of tissue renewal properties.Furthermore,we examine the possible cell rejuvenation strategies.Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.展开更多
Increasing evidence points towards a strong association between cerebrovascular dysfunction and neurodegenerative diseases in aging population.The global disease projection indicates that the healthcare burden derived...Increasing evidence points towards a strong association between cerebrovascular dysfunction and neurodegenerative diseases in aging population.The global disease projection indicates that the healthcare burden derived from these disease problems will continue to rise.Many traditional Chinese medicines(CMs)have been used to prevent and treat the multi-faceted diseases in China and other Asian countries.These herbs are potential rich sources of new leads that may also reveal previously unidentified mechanisms.Previously,our team has initiated a research program to analyze and characterize the bioactive extracts and pure natural components from the CMs using multipleexperimental models of vascular and neurodegenerative diseases.Some of the natural bioactive compounds have been further chemically modified to series of derivatives using different organic chemistry approaches(e.g.heterodimer and one-pot synthesis)and proven improved potency.The advantages of zebrafish modelfor in vivo high content screening of CMs will be presented.Our resultsprovide scientific rationales for clinical usage of the CMs and also probablylead to develop reproducible,higher potency and lower toxic agents for healthcare in the future.展开更多
基金supported by the Chinese Ministry of Science and Technology (2019YFA0801401 to B.Z.)the Chinese Academy of Sciences (XDB39000000 and QYZDY-SSW-SMC031 to B.Z.+1 种基金2019 Special Research Assistant Funding to Y.L.)the National Natural Science Foundation of China (32000559 to Y.L.)。
文摘Decades of investigation on DNA methylation have led to deeper insights into its metabolic mechanisms and biological functions.This understanding was fueled by the recent development of genome editing tools and our improved capacity for analyzing the global DNA methylome in mammalian cells.This review focuses on the maintenance of DNA methylation patterns during mitotic cell division.We discuss the latest discoveries of the mechanisms for the inheritance of DNA methylation as a stable epigenetic memory.We also highlight recent evidence showing the rapid turnover of DNA methylation as a dynamic gene regulatory mechanism.A body of work has shown that altered DNA methylomes are common features in aging and disease.We discuss the potential links between methylation maintenance mechanisms and diseaseassociated methylation changes.
文摘Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into distinct and specialized cells.As stem cells age,their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired.From a molecular perspective,these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration(i.e epigenomic profile)as well as changes in the tissue microenviroment,both into the niche and by systemic circulating factors.Strikingly,it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various agingassociated disorders.Therefore,understanding how resident stem cell age and affects near and distant tissues is fundamental.Here,we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number,function and phenotype that determine the loss of tissue renewal properties.Furthermore,we examine the possible cell rejuvenation strategies.Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.
文摘Increasing evidence points towards a strong association between cerebrovascular dysfunction and neurodegenerative diseases in aging population.The global disease projection indicates that the healthcare burden derived from these disease problems will continue to rise.Many traditional Chinese medicines(CMs)have been used to prevent and treat the multi-faceted diseases in China and other Asian countries.These herbs are potential rich sources of new leads that may also reveal previously unidentified mechanisms.Previously,our team has initiated a research program to analyze and characterize the bioactive extracts and pure natural components from the CMs using multipleexperimental models of vascular and neurodegenerative diseases.Some of the natural bioactive compounds have been further chemically modified to series of derivatives using different organic chemistry approaches(e.g.heterodimer and one-pot synthesis)and proven improved potency.The advantages of zebrafish modelfor in vivo high content screening of CMs will be presented.Our resultsprovide scientific rationales for clinical usage of the CMs and also probablylead to develop reproducible,higher potency and lower toxic agents for healthcare in the future.
