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Developmental Gerontology and Active Population Aging in China

China CDC weekly 2023年第8期5卷 184-187页

作者： Xiaoying Zheng Yanan Luo Binbin Su Ping He Chao Guo Yaohua Tian Shasha Han Chen Chen Yiran Wang Jufen Liu Jun Li School of Population Medicine and Public Health Chinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing MunicipalityChina Department of Global Health School of Public HealthPeking UniversityBeijing MunicipalityChina China Center for Health Development Studies Peking UniversityBeijing MunicipalityChina APEC Health Science Academy Peking UniversityBeijing MunicipalityChina Ministry of Education Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health(Incubating)School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Maternal and Child Health School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health Peking UniversityBeijing MunicipalityChina Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing MunicipalityChina Institute of Economics Chinese Academy of Social SciencesBeijing MunicipalityChina

Population Aging is an irreversible process in the development of modern society,which brings challenges to comprehensive modernized social governance.Population Aging is a“dualistic”development issue that not only leads to Aging of the labor force structure but also creates new demographic dividends.This study describes the core thoughts of developmental gerontology(DG),which provides new insight into the relationship between active Aging and comprehensive governance for modernized society.The development of DG will provide a feasible and sustainable path to integrate and coordinate the relationship between population Aging,society,and economy.

关键词： Aging irreversible Active

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Molecular hallmarks of long non-coding RNAs in Aging and its significant effect on Aging-associated diseases

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Neural Regeneration Research 2023年第5期18卷 959-968页

作者： Syed Aoun Mehmood Sherazi Asim Abbasi Abdullah Jamil Mohammad Uzair Ayesha Ikram Shanzay Qamar Adediji Ayomide Olamide Muhammad Arshad Peter J.Fried Milos Ljubisavljevic Ran Wang Shahid Bashir Department of Biological Sciences Faculty of Basic&Applied SciencesInternational Islamic UniversityIslamabadPakistan Department of Biological Sciences University of ArkansasFayettevilleARUSA Department of Pharmacology Government College UniversityFaisalabadPakistan Department of Bioinformatics and Biotechnology Government College UniversityFaisalabadPakistan Department of Chemistry Chulalongkorn UniversityThailand Department of Neurology Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive NeurologyBeth Israel Deaconess Medical Center(KS 158)Harvard Medical SchoolBostonMAUSA Department of Physiology College of Medicine and Health SciencesUnited Arab Emirates UniversityAl AinUnited Arab Emirates Department of Psychiatry The First Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Mental Health Institute of Hebei Medical University ShijiazhuangHebei ProvinceChina Neuroscience Center King Fahad Specialist HospitalDammamSaudi Arabia

Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing Aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying Aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in Aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the Aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and Aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, Aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in Aging.

关键词： Aging Alzheimer’s disease DNA sequence epigenetics immune non-coding RNA oligonucleotides telomere-associated

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Biomarkers of Aging

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Science China(Life Sciences) 2023年第5期66卷 893-1066页

作者： Aging Biomarker Consortium Hainan Bao Jiani Cao Mengting Chen Min Chen Wei Chen Xiao Chen Yanhao Chen Yu Chen Yutian Chen Zhiyang Chen Jagadish K Chhetri Yingjie Ding Junlin Feng Jun Guo Mengmeng Guo Chuting He Yujuan Jia Haiping Jiang Ying Jing Dingfeng Li Jiaming Li Jingyi Li Qinhao Liang Rui Liang Feng Liu Xiaoqian Liu Zuojun Liu Oscar Junhong Luo Jianwei Lv Jingyi Ma Kehang Mao Jiawei Nie Xinhua Qiao Xinpei Sun Xiaoqiang Tang Jianfang Wang Qiaoran Wang Siyuan Wang Xuan Wang Yaning Wang Yuhan Wang Rimo Wu Kai Xia Fu-Hui Xiao Lingyan Xu Yingying Xu Haoteng Yan Liang Yang Ruici Yang Yuanxin Yang Yilin Ying Le Zhang Weiwei Zhang Wenwan Zhang Xing Zhang Zhuo Zhang Min Zhou Rui Zhou Qingchen Zhu Zhengmao Zhu Feng Cao Zhongwei Cao Piu Chan Chang Chen Guobing Chen Hou-Zao Chen Jun Chen Weimin Ci Bi-Sen Ding Qiurong Ding Feng Gao Jing-Dong JHan Kai Huang Zhenyu Ju Qing-Peng Kong Ji Li Jian Li Xin Li Baohua Liu Feng Liu Lin Liu Qiang Liu Qiang Liu Xingguo Liu Yong Liu Xianghang Luo Shuai Ma Xinran Ma Zhiyong Mao Jing Nie Yaojin Peng Jing Qu Jie Ren Ruibao Ren Moshi Song Zhou Songyang Yi Eve Sun Yu Sun Mei Tian Shusen Wang Si Wang Xia Wang Xiaoning Wang Yan-Jiang Wang Yunfang Wang Catherine CL Wong Andy Peng Xiang Yichuan Xiao Zhengwei Xie Daichao Xu Jing Ye Rui Yue Cuntai Zhang Hongbo Zhang Liang Zhang Weiqi Zhang Yong Zhang Yun-Wu Zhang Zhuohua Zhang Tongbiao Zhao Yuzheng Zhao Dahai Zhu Weiguo Zou Gang Pei Guang-Hui Liu Aging Biomarker Consortium(ABC) Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Aging Biology Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China Clinic Center of Human Gene Research Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Clinical Research Center of Metabolic and Cardiovascular Disease Huazhong University of Science and TechnologyWuhan 430022China Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging Huazhong University of Science and TechnologyWuhan 430022China Stem Cell Translational Research Center Tongji HospitalTongji University School of MedicineShanghai 200065China Department of Nuclear Medicine Daping HospitalThird Military Medical UniversityChongqing 400042China CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China The Department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Key Laboratory of Regenerative Medicine of Ministry of Education Institute of Ageing and Regenerative MedicineJ

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.

关键词： Aging senescence biomarker clock

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Single-cell transcriptomic atlas of mouse cochlear Aging

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Protein & Cell 2023年第3期14卷 180-201页

作者： Guoqiang Sun Yandong Zheng Xiaolong Fu Weiqi Zhang Jie Ren Shuai Ma Shuhui Sun Xiaojuan He QiaoranWang zhejun ji Fang Cheng KaowenYan Ziyi Liu Juan Carloszpisuaemonte Jing Qu Si Wang Renjie Chai Guang-Hui Liu State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Bioelectronics Jiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSchool of Life Sciences and TechnologySoutheast UniversityNanjing 211189China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical University.Beijing100053China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital MedicalUniversityBeijing100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China China National Center for Bioinformation Beijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Gene Expression Laboratory Salk Institute for Biological StudiesLa JollaCA 92037USA Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Shandong Provincial Hospital and School of Laboratory Animal Science Shandong First Medical UniversityJinan 250000China

Progressive functional deterioration in the cochlea is associated with age-related hearing loss(ARHL).However,the cellular and molecular basis underlying cochlear Aging remains largely unknown.Here,we established a dynamic single-cell transcriptomic landscape of mouse cochlear Aging,in which we characterized Aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points.Overall,our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear Aging,highlights unexpected age-related transcriptional fluctuations in intermediate ceils localized in the stria vascularis(SV)and demonstrates that upregulation of endoplasmic reticulum(ER)chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with Aging.Our work suggests that targeting unfolded protein response pathways may help alleviate Aging-related sVatrophyand hencedelay theprogressionofARHL.

关键词： single-cell transcriptomic atlas mouse cochlea Aging

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Strengthening Systematic Research on Aging:Reflections from an Omics Perspective

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China CDC weekly 2022年第39期4卷 875-878页

作者： Xiaoying Zheng Chao Guo School of Population Medicine and Public Health Chinese Academy of Medical Sciences/Peking Union Medical CollegeBeijingChina APEC Health Science Academy Peking UniversityBeijingChina

Population Aging has become a global concern in population development.Challenges to good health in older ages are more complex than at any other age and require a comprehensive framework to move the science of Aging and health forward.In this paper,we describe an advanced and evolving conceptual framework that includes definitions,goals,disciplines,and a scope of human Aging omics(HAO)based on theories and methods of omics science.The development of HAO will bring a paradigm shift in research related to Aging and health by systematic identification,characterization,and quantification of all sets of health conditions and their complex relationships with the internal biomolecules and the external environment in the whole Aging process of human beings from birth to death throughout the lifespan.

关键词： Aging life goals

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Neuro faces of beneficial T cells:essential in brain,impaired in Aging and neurological diseases,and activated functionally by neurotransmitters and neuropeptides

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Neural Regeneration Research 2023年第6期18卷 1165-1178页

作者： Mia Levite Faculty of Medicine The Hebrew University of JerusalemCampus Ein KaremJerusalemIsrael Institute of Gene Therapy The Hadassah University Hospital-Ein KaremJerusalemIsrael

T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in Aging and multiple neurological diseases.Different T cell impairments are evident in Aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropept

关键词： Aging dopamine glutamate nerve-driven immunity neurological diseases neuropeptides neurotransmitters Personalized Adoptive Neuro-Immunotherapy T cells

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Single-nucleus transcriptomics reveals a gatekeeper role for FoxP1 in primate cardiac Aging

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Protein & Cell 2023年第4期14卷 279-293页

作者： Yiyuan Zhang Yandong Zheng Si Wang Yanling Fan Yanxia Ye Yaobin Jing Zunpeng Liu Shanshan Yang Muzhao Xiong Kuan Yang Jinghao Hu Shanshan Che Qun Chu Moshi Song Guang-Hui Liu Weiqi Zhang Shuai Ma Jing Qu National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 10o101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Aging Translational Medicine Center Xuanwu HospitalCapital Medical UniversityBeijing 100053China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China The Fifth People's Hospital of Chongqing Chongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China

Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac Aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular Aging at the single-cell resolution,and identify drivers for primate cardiac Aging and potential targets for intervention against cardiac Aging and associated diseases.

关键词： single-nucleus RNA-sequencing primate Aging FOxP1 cardiomyocyte

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The landscape of Aging

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Science China(Life Sciences) 2022年第12期65卷 2354-2454页

作者： Yusheng Cai Wei Song Jiaming Li Ying Jing Chuqian Liang Liyuan Zhang Xia Zhang Wenhui Zhang Beibei Liu Yongpan An Jingyi Li Baixue Tang Siyu Pei Xueying Wu Yuxuan Liu Cheng-Le Zhuang Yilin Ying Xuefeng Dou Yu Chen Fu-Hui Xiao Dingfeng Li Ruici Yang Ya Zhao Yang Wang Lihui Wang Yujing Li Shuai Ma Si Wang Xiaoyuan Song Jie Ren Liang Zhang Jun Wang Weiqi Zhang Zhengwei Xie Jing Qu Jianwei Wang Yichuan Xiao Ye Tian Gelin Wang Ping Hu Jing Ye Yu Sun Zhiyong Mao Qing-Peng Kong Qiang Liu Weiguo Zou Xiao-Li Tian Zhi-Xiong Xiao Yong Liu Jun-Ping Liu Moshi Song Jing-Dong J.Han Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Frontier Science Center for Immunology and Metabolism Medical Research InstituteCollege of Life SciencesWuhan UniversityWuhan 430071China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Peking University International Cancer Institute Peking University Health Science CenterPeking UniversityBeijing 100191China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China School of Pharmaceutical Sciences Beijing Advanced Innovation Center for Structural BiologyMinistry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologyTsinghua UniversityBeijing 100084China Colorectal Cancer Center/Department of Gastrointestinal Surgery Shanghai Tenth People’s Hospital Affiliated to Tongji UniversityShanghai 200072China Department of Geriatrics Medical Center on Aging of Shanghai Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China International Laboratory in Hematology and Cancer Shanghai Jiaotong University School of Med

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.

关键词： Aging mechanism intervention

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Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in Aging and Alzheimer’s disease

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Neural Regeneration Research 2022年第8期17卷 1645-1651页

作者： Angie K.Torres Bastián I.Rivera Catalina M.Polanco Claudia Jara Cheril Tapia-Rojas Laboratory of Neurobiology of Aging Centro de Biología Celular y Biomedicina(CEBICEM)Facultad de Medicina y CienciaUniversidad San SebastiánSede Los LeonesSantiagoChile

During normal Aging,there is a decline in all physiological functions in the organism.One of the most affected organs is the brain,where neurons lose their proper synaptic function leading to cognitive impairment.Aging is one of the main risk factors for the development of neurodegenerative diseases,such as Alzheimer’s disease.One of the main responsible factors for synaptic dysfunction in Aging and neurodegenerative diseases is the accumulation of abnormal proteins forming aggregates.The most studied brain aggregates are the senile plaques,formed by Aβpeptide;however,the aggregates formed by phosphorylated tau protein have gained relevance in the last years by their toxicity.It is reported that neurons undergo severe mitochondrial dysfunction with age,with a decrease in adenosine 5′-triphosphate production,loss of the mitochondrial membrane potential,redox imbalance,impaired mitophagy,and loss of calcium buffer capacity.Interestingly,abnormal tau protein interacts with several mitochondrial proteins,suggesting that it could induce mitochondrial dysfunction.Nevertheless,whether tau-mediated mitochondrial dysfunction occurs indirectly or directly is still unknown.A recent study of our laboratory shows that phosphorylated tau at Ser396/404(known as PHF-1),an epitope commonly related to pathology,accumulates inside mitochondria during normal Aging.This accumulation occurs preferentially in synaptic mitochondria,which suggests that it may contribute to the synaptic failure and cognitive impairment seen in aged individuals.Here,we review the main tau modifications promoting mitochondrial dysfunction,and the possible mechanism involved.Also,we discuss the evidence that supports the possibility that phosphorylated tau accumulation in synaptic mitochondria promotes synaptic and cognitive impairment in Aging.Finally,we show evidence and argue about the presence of phosphorylated tau PHF-1 inside mitochondria in Alzheimer’s disease,which could be considered as an early event in the neurodegenerative process.Thus,phosphoryl

关键词： age pathology Aging Alzheimer’s disease hippocampus memory mitochondria PHF-1 phosphorylated tau synaptic mitochondria tau

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Single-cell transcriptomic profiling of the hypothalamic median eminence during Aging

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Journal of Genetics and Genomics 2022年第6期49卷 523-536页

作者： Zhen-Hua Chen Si Li Mingrui Xu Candace CLiu Hongying Ye Ben Wang Qing-Feng Wu State Key Laboratory of Molecular Development Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Department of Pathology Stanford University School of MedicineStanfordCA 94305USA Department of Endocrinology and Metabolism Huashan HospitalFudan UniversityShanghai 200040China Department of Obstetrics and Gynecology Baoding Second Central HospitalBaodingHebei 072750China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesBeijing 100101China Chinese Institute for Brain Research Beijing 102206China Beijing Children’s Hospital Capital Medical UniversityBeijing 100045China

Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The Aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrine systems,may impair hormone release,energy homeostasis,and central sensing of circulating molecules,leading to systemic and reproductive Aging.However,the molecular and cellular features of ME Aging remain largely unknown.Here,we describe the transcriptional landscape of young and middleaged mouse ME at single-cell resolution,revealing the common and cell type-specific transcriptional changes with age.The transcriptional changes in cell-intrinsic programs,cell-cell crosstalk,and cellextrinsic factors highlight five molecular features of ME Aging and also implicate several potentially druggable targets at cellular,signaling,and molecular levels.Importantly,our results suggest that vascular and leptomeningeal cells may lead the asynchronized Aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome.Together,our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the Aging process,which will facilitate our understanding of brain Aging and provide clues for efficient anti-Aging intervention at the middle-aged stage.

关键词： Hypothalamic median eminence Single-cell transcriptomic analysis Vascular and leptomeningeal cells Aging

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