Remarkable progress in ageing research has been achieved over the past decades.General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ...Remarkable progress in ageing research has been achieved over the past decades.General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing.Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli,representing current hotspots as they not only(re-)shape the individual cell identity,but also involve in cell fate decision.This review focuses on the present findings and emerging concepts in epigenetic,inflammatory,and metabolic regulations and the consequences of the ageing process.Potential therapeutic interventions targeting cell senescence and regulatory mechanisms,using state-of-the-art techniques are also discussed.展开更多
Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human dise...Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.展开更多
Susceptibility of gastrointestinal dysmotility increases with age-associated colonic degeneration.A paucity of remedies reversing colonic degeneration per se hinders the fundamental relief of symptoms.Here we discover...Susceptibility of gastrointestinal dysmotility increases with age-associated colonic degeneration.A paucity of remedies reversing colonic degeneration per se hinders the fundamental relief of symptoms.Here we discovered the correlation between colon degeneration and altered nicotinamide adenine dinucleotide(NAD)level in aged mice.Compared to 3-month-old young controls,2-year-old mice showed a spectrum of degenerative colonic phenotypes and exhibited a significant elongated transit time and slowed stool frequency in the context of Lomotil-induced slow-transit constipation.Despite upregulated colonic tryptophan hydroxylases expression,serotonin release and expression of colon-predominant type IV serotonin receptor,reduced viability of interstitial cells of Cajal while enhanced aquaporins(Aqp1,3 and 11)led to a less colonic motility and increased luminal dehydration in aged mice.Notably,this colonic degeneration was accompanied with reduced key NAD^(+)-generating enzyme expression and lowered NAD^(+)/NADH ratio in aged colon.Three-month continuous administration of beta nicotinamide mononucleotide,a NAD^(+)precursor,elevated colonic NAD^(+)level and improved defecation in aged mice.In contrast,pharmacological inhibition of nicotinamide phosphoribosyltransferase,the rate-limiting enzyme for NAD^(+)biosynthesis,induced a reduction in colonic NAD content and impaired gastrointestinal function in young mice.Taken together,these findings suggest the beneficial effect of NAD^(+)in maintaining colonic homoeostasis and reactivating NAD^(+)biosynthesis may represent a promising strategy to counteract age-related gastrointestinal degeneration.展开更多
基金This work was supported by Grants 2016YFA0100602,2017YFA0103302,and 2018YFA0109300 from the National Key Research and Development Program of ChinaGrants 81525010,81770155,91749117,91749203,81901403,82030039,82022026,and 82071572 from the National Natural Science Foundation of China+3 种基金Grant 2C32003 from Opening Project of Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang ProvinceGrant 2019B151502008 from the Science Foundation for Distinguished Young Scholars of Guangdong ProvinceGrant 2018GZR110103002 from Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGrant 2017ZT07S347 from the Program for Guangdong Introducing Innovative and Enterpreneurial Teams.
文摘Remarkable progress in ageing research has been achieved over the past decades.General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing.Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli,representing current hotspots as they not only(re-)shape the individual cell identity,but also involve in cell fate decision.This review focuses on the present findings and emerging concepts in epigenetic,inflammatory,and metabolic regulations and the consequences of the ageing process.Potential therapeutic interventions targeting cell senescence and regulatory mechanisms,using state-of-the-art techniques are also discussed.
基金supported by the National Natural Science Foundation of China(31871380,32000500,32070730,32170756,32170804,81330008,81671377,81725010,81725010,81872874,81921006,81922027,81971312,81991512,82030041,82103167,82122024,82125009,82125011,82130044,91749126,91949101,91949207,92049302)the National Key Research and Development Program of China(2017YFA0506400,2018YFA0800200,2018YFA0800700,2018YFA0900200,2018YFC2000100,2018YFC2000400,2018YFE-0203700,20192ACB70002,2019YFA0802202,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002800,2020YFC-2002900,2021ZD0202401)+11 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100,XDA16010603,XDA16020400,XDB29020000,XDB39000000,XDB39000000,XDB39030300)the China Association for Science and Technology(2021QNRC001)the Beijing Municipal Science and Technology Commission(Z200022)the Natural Science Foundation of Shanghai(21JC1406400)the Key Programs of the Jiangxi ProvinceChina(20192ACB70002)the“Shu Guang”Project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation(19SG18)the Shanghai Sailing Program(22YF1434300)the Research Project of Joint Laboratory of University of Science and Technology of China and Anhui Mental Health Center(2019LH03)the Fundamental Research Funds for the Central Universities(WK2070210004)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(YESS20210002)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022083)。
文摘Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.
基金This work was supported by grants from the Natural Science Foundation of Zhejiang province(Y13H030005)to QS,National Natural Science Foundation of China(81400221)Hangzhou Normal University(PF14002004017)to XZ。
文摘Susceptibility of gastrointestinal dysmotility increases with age-associated colonic degeneration.A paucity of remedies reversing colonic degeneration per se hinders the fundamental relief of symptoms.Here we discovered the correlation between colon degeneration and altered nicotinamide adenine dinucleotide(NAD)level in aged mice.Compared to 3-month-old young controls,2-year-old mice showed a spectrum of degenerative colonic phenotypes and exhibited a significant elongated transit time and slowed stool frequency in the context of Lomotil-induced slow-transit constipation.Despite upregulated colonic tryptophan hydroxylases expression,serotonin release and expression of colon-predominant type IV serotonin receptor,reduced viability of interstitial cells of Cajal while enhanced aquaporins(Aqp1,3 and 11)led to a less colonic motility and increased luminal dehydration in aged mice.Notably,this colonic degeneration was accompanied with reduced key NAD^(+)-generating enzyme expression and lowered NAD^(+)/NADH ratio in aged colon.Three-month continuous administration of beta nicotinamide mononucleotide,a NAD^(+)precursor,elevated colonic NAD^(+)level and improved defecation in aged mice.In contrast,pharmacological inhibition of nicotinamide phosphoribosyltransferase,the rate-limiting enzyme for NAD^(+)biosynthesis,induced a reduction in colonic NAD content and impaired gastrointestinal function in young mice.Taken together,these findings suggest the beneficial effect of NAD^(+)in maintaining colonic homoeostasis and reactivating NAD^(+)biosynthesis may represent a promising strategy to counteract age-related gastrointestinal degeneration.