Dear Editor,Learning-induced expression of activity-dependent genes,especially immediate-early genes(IEGs),is required for the conversion of experience-induced neuronal activity into long-term memory[1].Neuronal Per-A...Dear Editor,Learning-induced expression of activity-dependent genes,especially immediate-early genes(IEGs),is required for the conversion of experience-induced neuronal activity into long-term memory[1].Neuronal Per-Arnt-Sim domain protein 4(Npas4)is one of the most rapidly induced IEGs,functioning as a transcription factor to regulate the activity-dependent expression of other IEGs,such as activityregulated cytoskeleton associated protein(Arc),Fos protooncogene,and early growth response 1(Egrl)[1].展开更多
The entorhinal cortex(EC)-hippocampal(HPC)circuit is particularly vulnerable to Alzheimer's disease(AD)pathol-ogy,yet the underlying molecular mechanisms remain unclear.By employing the high-depth sequencing strat...The entorhinal cortex(EC)-hippocampal(HPC)circuit is particularly vulnerable to Alzheimer's disease(AD)pathol-ogy,yet the underlying molecular mechanisms remain unclear.By employing the high-depth sequencing strategy Smart-seq2,we tracked gene expression changes across various neuron types within this circuit at different stages of AD pathology.We observed a decrease in the extent of gene expression changes in AD versus wild-type(WT)mice as the disease advanced.Functionally,we demonstrate that both mitochondrial and ribosomal pathways were increasingly activated,while neuronal pathways were inhibited with AD progression.Our findings indicate that the reduction of EC-stellate cells disrupts Meg3-mediated energy metabolism,contributing to energy dysfunction in AD.Additionally,we identified GFAP-positive neurons as a distinct population of disease-associated neurons,exhibiting a loss of neuronal-like characteristics,alongside the emergence of glia-and stem-like features.The num-ber of GFAP-positive neurons increased with AD progression,a trend consistently observed in both AD model mice and AD patients.In summary,this study identifies and characterizes GFAP-positive neurons as a novel subtype of disease-associated neurons in AD pathology,providing insights into their potential role in disease progression.展开更多
DearEditor,Brain aging is associated with a decrease in cognitive function,which is often accompanied by defective changes in mitochondrial morphology and reduction in mitochondrial function(Faitg et al.,2021).The mai...DearEditor,Brain aging is associated with a decrease in cognitive function,which is often accompanied by defective changes in mitochondrial morphology and reduction in mitochondrial function(Faitg et al.,2021).The main function of mitochondria is to produce energy in the form of ATP,which is vital to fulfill high energy demand of neurons,mainly for synaptic processes(Lee et al.,2018).Mitochondrial dysfunction acts as a key factor for age-related cognitive decline(Grimm and Eckert,2017).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
Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
基金supported by the National Key R&D Program of China(2021YFA0804900 and 2020YFA0509300)the National Natural Science Foundation of China(82125009,82330045,82071185,32100794,92149303,and 32121002)+5 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39000000)a CAS Project for Young Scientists in Basic Research(YSBR-013)Plans for Major Provincial Science&Technology Projects(202303a07020004)the Collaborative Innovation Program of Hefei Science Center,CAS(2022HSC-CIP003)Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYZD20220003)USTC Research Funds of the Double First-Class Initiative.
文摘Dear Editor,Learning-induced expression of activity-dependent genes,especially immediate-early genes(IEGs),is required for the conversion of experience-induced neuronal activity into long-term memory[1].Neuronal Per-Arnt-Sim domain protein 4(Npas4)is one of the most rapidly induced IEGs,functioning as a transcription factor to regulate the activity-dependent expression of other IEGs,such as activityregulated cytoskeleton associated protein(Arc),Fos protooncogene,and early growth response 1(Egrl)[1].
基金supported by the National Natural Science Foundation of China(Grant Nos.82125009,82330045,32121002,82071185,82172061,and 92149303)the National Key R&D Program of China(Grant Nos.2020YFA0509300,2021YFA0804900,and 2022YFC2703102)+4 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39000000)CAS Project for Young Scientists in Basic Research(YSBR-013),Plans for Major Provincial Science&Technology Projects(202303a07020004)Hefei Comprehensive National Science Center Hefei Brain Project,Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYZD20220003)the Major Frontier Research Project of the University of Science and Technology of China(LS9100000002)S&T Program of Shijiazhuang(235790429H).
文摘The entorhinal cortex(EC)-hippocampal(HPC)circuit is particularly vulnerable to Alzheimer's disease(AD)pathol-ogy,yet the underlying molecular mechanisms remain unclear.By employing the high-depth sequencing strategy Smart-seq2,we tracked gene expression changes across various neuron types within this circuit at different stages of AD pathology.We observed a decrease in the extent of gene expression changes in AD versus wild-type(WT)mice as the disease advanced.Functionally,we demonstrate that both mitochondrial and ribosomal pathways were increasingly activated,while neuronal pathways were inhibited with AD progression.Our findings indicate that the reduction of EC-stellate cells disrupts Meg3-mediated energy metabolism,contributing to energy dysfunction in AD.Additionally,we identified GFAP-positive neurons as a distinct population of disease-associated neurons,exhibiting a loss of neuronal-like characteristics,alongside the emergence of glia-and stem-like features.The num-ber of GFAP-positive neurons increased with AD progression,a trend consistently observed in both AD model mice and AD patients.In summary,this study identifies and characterizes GFAP-positive neurons as a novel subtype of disease-associated neurons in AD pathology,providing insights into their potential role in disease progression.
基金supported by the National Natural Science Foundation of China (Grant Nos.82125009,U19A2034,31871082,91849101,32121002,82071185,32100794 and 92149303)the National Key R&D Program of China (2020YFA0509300,2021YFA0804900)+4 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB39000000)CAS Project for Young Scientists in Basic Research (YSBR-013)Collaborative Innovation Program of Hefei Science Center,CAS (2022HSC-CIP003)the Fundamental Research Funds for the Central Universities (YD2070002011,WK2070000168)Institute of Health and Medicine,Hefei Comprehensive National Science Center (QYZD20220003).
文摘DearEditor,Brain aging is associated with a decrease in cognitive function,which is often accompanied by defective changes in mitochondrial morphology and reduction in mitochondrial function(Faitg et al.,2021).The main function of mitochondria is to produce energy in the form of ATP,which is vital to fulfill high energy demand of neurons,mainly for synaptic processes(Lee et al.,2018).Mitochondrial dysfunction acts as a key factor for age-related cognitive decline(Grimm and Eckert,2017).
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supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+14 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA141)the Science and Technology Major Project of Hunan Provincial Science and Technology Department(2021SK1010)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Natural Science Foundation of Sichuan Province(2023NSFSC0003)Yunnan Fundamental Research Project(202201AS070080)the State Key Laboratory of Membrane Biology。
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
