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Distinct molecular profiles of skull bone marrow in health and neurological disorders

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四川生理科学杂志 2023年第9期45卷 1704-1704页

作者： Zeynep Ilgin Kolabas Institute for Tissue Engineering and Regenerative Medicine (iTERM) Helmholtz Center Neuherberg Munich Germany Institute for Stroke and Dementia Research LMU University Hospital Ludwig-Maximilians University Munich Munich Germany Graduate School of Systemic neurosciences (GSN) Munich Germany Institute of Computational Biology Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany Division of Mental Health in Older Adults and Alzheimer Therapy and Research Center Department of Psychiatry and Psychotherapy University Hospital Ludwig Maximilian University Munich 80336 Munich Germany German Center for Neurodegenerative Diseases (DZNE) Munich Munich Germany Ageing Epidemiology (AGE) Research Unit School of Public Health Imperial College London London UK Munich Cluster for Systems Neurology (SyNergy) Munich Germany Sheffield Institute for Translational Neuroscience University of Sheffield Sheffield UK Department of Nuclear Medicine University Hospital Ludwig-Maximilians-Universität München Munich Germany Institute for Diabetes and Obesity Helmholtz Center Munich and German Center for Diabetes Research (DZD) 85764 Neuherberg Germany Munich Medical Research School (MMRS) 80336 Munich Germany Helmholtz Pioneer Campus (HPC) Helmholtz Munich Neuherberg Germany Wellcome Sanger Institute Cambridge UK School of Computation Information and Technology (CIT) TUM Boltzmannstr. 3 85748 Garching Germany Department of Radiology University Hospital LMU Munich Munich Germany Charité - Universitätsmedizin Berlin Department of Rheumatology and Clinical Immunology Berlin Germany Immune Dynamics Deutsches Rheuma-Forschungszentrum (DRFZ) a Leibniz Institute Berlin Germany Biomedical Center (BMC) Core Facility Flow Cytometry Faculty of Medicine LMU Munich Munich Germany Institute for Diabetes and Cancer Helmholtz Munich Munich Germany Institute of Neuroradiology University Hospital LMU Munich Germany Institute of Diabetes and Regenerat

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections (SMCs) compared with veins. Last, using translocator protein positronemission tomography (TSPO-PET) imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile and anatomical and functional connections of the skull show its potential as a site for diagnosing, monitoring, and treating brain diseases.

关键词： neurological disorders diseases

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研究神经胶质细胞的新兴技术

神经损伤与功能重建 2020年第10期15卷 F0003-F0003页

作者： Hélène Hirbec Nicole Déglon Lynette C Foo Inbal Goshen Jaime Grutzendler Emilie Hangen Tirzah Kreisel Nathalie Linck Julien Muffat Sara Regio Sybille Rion Carole Escartin 杜一星 Institute for Functional Genomics(IGF) University of MontpellierCNRSINSERMMontpellierFrance Laboratory of Neurotherapies and Neuromodulation Department of Clinical NeuroscienceLausanne University HospitalUniversity of LausanneLausanneSwitzerland Laboratory of Neurotherapies and Neuromodulation Neuroscience Research CenterLausanne University Hospital and University of LausanneLausanneSwitzerland Neuroimmunology and Neurodegeneration Section The Neuroscience and Rare Diseases Discovery and Translational AreaF.Hoffman-La RocheBaselSwitzerland Edmond and Lily Safra Center for Brain Sciences The Hebrew University of JerusalemJerusalemIsrael Department of Neurology Yale University School of MedicineNew HavenConnecticutUSA Department of Neuroscience Yale University School of MedicineNew HavenConnecticutUSA Commissariatà l'Energie Atomique et aux Energies Alternatives Département de la Recherche FondamentaleInstitut de Biologie François JacobMIRCenFontenay-aux-RosesFrance Centre National de la Recherche Scientifique Neurodegenerative Diseases LaboratoryUniversitéParis-SudUniversitéParis-SaclayUMR 9199Fontenay-aux-RosesFrance Program in neurosciences and Mental Health The Hospital for Sick Childrenand Department of Molecular GeneticsThe University of TorontoTorontoCanada 不详

大脑的发育、生理功能和病理与神经元和不同类型的神经胶质细胞(如星形胶质细胞、小胶质细胞、少突胶质细胞和少突胶质细胞的前体细胞等)之间的相互作用密切相关。研究脑功能及其功能障碍,除了神经元之外,还需要对不同类型的神经胶质细... 详细信息

大脑的发育、生理功能和病理与神经元和不同类型的神经胶质细胞(如星形胶质细胞、小胶质细胞、少突胶质细胞和少突胶质细胞的前体细胞等)之间的相互作用密切相关。研究脑功能及其功能障碍,除了神经元之外,还需要对不同类型的神经胶质细胞进行研究。近年来,多项技术突破使“神经胶质科学家”能够解决新的具有挑战性的生物学问题。这些技术发展使得以中/高含量工作流研究特定细胞类型的作用成为可能,并在保存完好的环境中对其相互作用进行精细的分析。本综述阐明了几种可能揭示神经胶质细胞在特定脑功能或疾病中作用的尖端实验方法。这些实验方法包括高级细胞培养,诱导多能干细胞(iPSC)衍生的人神经胶质细胞,病毒载体,原位胶质细胞成像,光学遗传学和化学遗传学方法,以及高内涵分子分析。本文还阐述了某些技术的临床转化,通过特定的脑成像方法以监控患者的神经胶质细胞。本文亦讨论了每种技术的优点,缺陷和未来发展,并提供了选定的示例以说明现在如何可以解决特定的“胶质生物学”问题。

关键词：神经胶质细胞少突胶质细胞小胶质细胞星形胶质细胞脑功能细胞培养细胞类型脑成像

小胶质细胞控制成年小鼠海马中的谷氨酸能突触

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神经损伤与功能重建 2021年第10期16卷 F0003-F0003页

作者： Bernadette Basilico Laura Ferrucci Patrizia Ratano Maria T Golia Alfonso Grimaldi Maria Rosito Valentina Ferretti Ingrid Reverte Caterina Sanchini Maria C Marrone Maria Giubettini Valeria De Turris Debora Salerno Stefano Garofalo Marie-Kim St-Pierre Micael Carrier Massimiliano Renzi Francesca Pagani Brijesh Modi Marcello Raspa Ferdinando Scavizzi Cornelius T Gross Silvia Marinelli Marie-Ève Tremblay Daniele Caprioli Laura Maggi Cristina Limatola Silvia Di Angelantonio Davide Ragozzino Department of Physiology and Pharmacology Sapienza University of RomeRomeItaly. Neurophysiology and Neuropharmacology Inflammaging Unit IRCCS NeuromedMediterranean Neurological InstitutePozzilliISItaly. Center for Life Nano-and Neuro-science Istituto Italiano di TecnologiaRomeItaly. Dipartimento di Biologia e Biotecnologie“Charles Darwin” Sapienza University of RomeRomeItaly. Santa Lucia Foundation(IRCCS Fondazione Santa Lucia) RomeItaly. European Brain Research Institute(EBRI)‘Rita Levi-Montalcini’ RomeItaly. CrestOptics S.p.A RomeItaly. Centre de Recherche du CHU de Québec Axe Neurosciences QuébecQuebec CityCanada. Département de Médecine Moléculaire UniversitéLaval QuébecQuebec CityCanada.1 National Research Council Institute of Biochemistry and Cell Biology(CNR-IBBC/EMMA/Infrafrontier/IMPC)International Campus“A.Buzzati-Traverso”Monterotondo(Rome)Italy.1 Epigenetics and Neurobiology Unit European Molecular Biology Laboratory(EMBL)MonterotondoItaly.1 Division of Medical Sciences University of VictoriaVictoriaCanada.1 Department of Physiology and Pharmacology Sapienza UniversityLaboratory affiliated to Istituto Pasteur ItaliaRomeItaly.

小胶质细胞是调节大脑突触发育和可塑性的重要细胞类型,但其影响突触的正常功能的机制尚不清楚。在本研究中,我们通过PLX5622造成小胶质细胞耗竭,并观察其对成年野生型小鼠海马CA3-CA1突触的影响。在小胶质细胞耗竭后,与树突棘密度降低... 详细信息

小胶质细胞是调节大脑突触发育和可塑性的重要细胞类型,但其影响突触的正常功能的机制尚不清楚。在本研究中,我们通过PLX5622造成小胶质细胞耗竭,并观察其对成年野生型小鼠海马CA3-CA1突触的影响。在小胶质细胞耗竭后,与树突棘密度降低相关的自发和诱发谷氨酸能活动的减少,出现未成熟突触特征以及突触的可塑性提高。小胶质细胞耗竭的小鼠在新物体识别任务的获取方面表现出缺陷。海马星形胶质细胞出现增生,但并没有神经炎症反应。在Cx3cr1-/-小鼠中,PLX不能导致海马出现上述改变。这说明CX3CL1/CX3CR1轴在小胶质细胞对突触功能的控制中有重要作用。PLX5622停用后,小胶质细胞的重新增殖,海马突触恢复,小鼠的学习功能也出现恢复。综上所述,小胶质细胞对维持成人大脑的突触的正常功能用重要的作用,去除小胶质细胞会导致谷氨酸能突触组织和活动的可逆变化。

关键词：谷氨酸能传递海马体学习小胶质细胞神经元-小胶质细胞相互作用突触

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皮质下小血管病诊断的共识声明

国际脑血管病杂志 2016年第6期24卷 481-496页

作者： Gary A Rosenberg Anders Wallin Joanna M Wardlaw Hugh S Markus Joan Montaner Leslie Wolfson Costantino Iadecola Berislav V Zlokovic Anne Joutel Martin Dichgans Marco Duering Reinhold Schmidt Amos D Korczyn Lea T Grinberg Helena C Chui Vladimir Hachinski 王训师张劼陈涵丰俞娅美徐子奇罗本燕 Department of Neurology University of New Mexico Albuquerque New Mexico USA Institute of Neuroscience and Physiology Sahlgrenska Academy Gothenburg University Gothenburg Sweden Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK Department of Clinical neurosciences University of Cambridge Cambridge UK Neurovascular Research Laboratory Vail d'Hebron Research Institute Universitat Auto'noma de Barcelona Barcelona Spain Department of Neurology University of Connecticut Health Center Farmington Connecticut USA Feil Family Brain and Mind Research Institute Weill Cornell Medical College New York New York USA Department of Physiology and Biophysics Zilkha Neurogenetic Institute Keck School of Medicine University of Southern Califomia Los Angeles California USA INSERM U1161 Paris France Institute for Stroke and Dementia Research Klinikum der Universitat Mtinchen Munich Germany Department of Neurology Medical University of Graz Graz Austria Tel-Aviv University Medical School Ramat Aviv Israel Department of Neurology Memory and Aging Center and Department of Pathology University of Califomia San Francisco California USA University of Sao Paulo Medical School Sao Paulo Brazil Department of Neurology University of Southern California Medical School Los Angeles California USA Department of Clinical Neurological Sciences University Hospital University of Western Ontario London Ontario Canada 浙江大学医学院附属第一医院杭州310003

血管性认知损害是用于描述一组涉及大血管和小血管的散发性和遗传性异质性疾病的诊断术语。皮质下小血管病可导致腔隙性梗死和进行性白质损害。被称为宾斯旺格病（Binswanger＇s disease, BD）的进行性白质损害患者构成了从单纯血管性... 详细信息

血管性认知损害是用于描述一组涉及大血管和小血管的散发性和遗传性异质性疾病的诊断术语。皮质下小血管病可导致腔隙性梗死和进行性白质损害。被称为宾斯旺格病（Binswanger＇s disease, BD）的进行性白质损害患者构成了从单纯血管性疾病到合并神经变性病变的疾病谱。BD患者是一个相对同质性的亚组，存在缺氧缺血、腔隙性梗死和炎症，它们协同作用破坏血脑屏障和髓鞘。通过临床、脑脊液、神经心理学和影像学检查获得的多模式疾病标记物能促进该亚组患者的鉴别。本共识声明确定了一系列基于基础病理学改变的潜在生物学标记物，这将有助于诊断以及将来协作性治疗试验的患者选择。

关键词：宾斯旺格病血脑屏障通透性脑脊液炎症白质疏松

AME证据系列001--转化医学协会:脓毒症诊断和早期识别的临床实践指南

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临床与病理杂志 2016年第10期36卷 1467-1476页

作者： Zhongheng Zhang Nathan J.Smischney Haibo Zhang Sven Van Poucke Panagiotis Tsirigotis Jordi Rello Patrick M.Honore Win Sen Kuan Juliet June Ray Jiancang Zhou You Shang Yuetian Yu Christian Jung Chiara Robba Fabio Silvio Taccone Pietro Caironi David Grimaldi Stefan Hofer George Dimopoulos Marc Leone Sang-Bum Hong Mabrouk Bahloul Laurent Argaud Won Young Kim Herbert D.Spapen Jose Rodolfo Rocco 张建成(译) 尚游(译) 钟鸣(校) Department of Emergency Medicine Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016 Department of Critical Care Medicine Jinhua Hospital of Zhejiang UniversityJinhua Zhejiang 321000 Department of Anesthesiology Mayo ClinicRochesterMNUSA Keenan Research Center for Biomedical Science of St.Michael's Hospital Departments of Anesthesia and PhysiologyInterdepartmental Division of Critical Care MedicineUniversity of TorontoTorontoONCanada Departments of Anesthesiology Critical CareEmergency Medicine and Pain TherapyZiekenhuis Oost-Limburgy GenkBelgium 2nd Department of Internal Medicine Attikcon University HospitalMedical SchoolNational and Kapodistrian University of AthensAthensGreece CIBERES Vall d'Hebron Institut of ResearchUniversitat Autonoma de BarcelonaSpain Universitair Ziekenhuis Brussely Vrije Universiteit Brussel Brussels BrusselsBelgium Emergency Medicine Department National University HospitalNational University Health SystemSingapore and the Department of SurgeryYong Loo Lin School of MedicineNational University of SingaporeSingapore DeWitt Daughtry Family Department of Surgery Jackson Memorial HospitalUniversity of Miami Leonard M.Miller School of MedicineMiamiFLUSA Department of Critical Care Medicine Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016 Department of Critical Care Medicine Union HospitalTongji Medical CollegueHuazhong University of Science and TechnologyWuhan 430022 Department of Critical Care Medicine Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200001 University Hospital Dusseldorf Heinrich-Heine-University DusseldorfMedical FacultyDivision of CardiologyPulmonology and Vascular MedicineDusseldorfGermany neurosciences Critical Care Unit Addenbrooke's HospitalCambridgeUK Department of Intensive Care Hopital ErasmeUniversite Libre de Bruxelles(ULB)BrusselsBelgium Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti Fondazione IRCCS Ca'Granda-Ospedale

脓毒症是一种由感染引起的异质性疾病,感染触发了一系列复杂的局部或者全身的免疫炎症反应,引起多器官功能衰竭,发病率和病死率显著升高。由于至今仍然没有诊断脓毒症的金标准,所以脓毒症的临床诊断仍是一个难题。因此,脓毒症的临床诊... 详细信息

脓毒症是一种由感染引起的异质性疾病,感染触发了一系列复杂的局部或者全身的免疫炎症反应,引起多器官功能衰竭,发病率和病死率显著升高。由于至今仍然没有诊断脓毒症的金标准,所以脓毒症的临床诊断仍是一个难题。因此,脓毒症的临床诊断需要不断改变来满足临床和研究的要求。然而,尽管有许多新型的生物标记和筛选工具去预测脓毒症发生的风险,但是这些措施的诊断价值和有效性不足以让人满意,并且没有充分的证据去建议临床使用这些新技术。因此,脓毒症的临床诊断标准需要定期更新去适应不断产生的新证据。这篇综述旨在呈现当前脓毒症的诊断和早期识别方面的最新研究证据。临床运用不同的诊断方法的推荐意见依赖于推荐、评价、发展和评估分级体系(Grades of Recommendation Assessment,Development and Evaluation,GRADE),因为大部分的研究是观察性研究,并没有对这些方法进行可靠评估,采用的是两步推理方法。未来需要更多研究来确认或者反驳某一特殊的指标检测,同时应该直接采用相关病人的结果数据。

关键词：脓毒症早期识别诊断

Genetic mechanisms of critical illness in Covid-19

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四川生理科学杂志 2020年第4期42卷 455-455页

作者： Erola Pairo-Castineira Roslin Institute University of Edinburgh Edinburgh UK MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Genomics England London UK Centre for Inflammation Research The Queen’s Medical Research Institute University of Edinburgh Edinburgh UK Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Edinburgh Clinical Research Facility Western General Hospital University of Edinburgh Edinburgh UK Intensive Care National Audit & Research Centre London UK Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia Biostatistics Group School of Life Sciences Sun Yat-sen University Guangzhou China The Crick Institute London UK Intensive Care Unit Royal Infirmary of Edinburgh Edinburgh UK School of Life Sciences Westlake University Hangzhou China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou China Wellcome Centre for Human Genetics University of Oxford Oxford UK Department of Medicine University of Cambridge Cambridge UK Department of Intensive Care Medicine Guy’s and St Thomas’ NHS Foundation Trust London UK School of Immunology and Microbial Sciences King’s College London London UK NIHR Health Protection Research Unit for Emerging and Zoonotic Infections Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool UK MRC-University of Glasgow Centre for Virus Research Institute of Infection Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow UK William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK Centre for Tropical Medicine and Global Health Nuffield Department of Medicine University of Oxford Oxford UK Clinical Research Centre at St Vincent’s University Hospital Un

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by *** genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC(Genetics Of Mortality In Critical Care)genome-wide association study(GWAS)in 2244 critically ill Covid-19 patients from 208 UK intensive care units(ICUs).We identify and replicate novel genome-wide significant associations,on chr12q24.13(rs10735079,p=1.65[Formula:see text]10-8)in a gene cluster encoding antiviral restriction enzyme activators(OAS1,OAS2,OAS3),on chr19p13.2(rs2109069,p=2.3[Formula:see text]10-12)near the gene encoding tyrosine kinase 2(TYK2),on chr19p13.3(rs2109069,p=3.98[Formula:see text]10-12)within the gene encoding dipeptidyl peptidase 9(DPP9),and on chr21q22.1(rs2236757,p=4.99[Formula:see text]10-8)in the interferon receptor gene *** identify potential targets for repurposing of licensed medications:using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2,and high expression of TYK2,to life-threatening disease;transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe *** results identify robust genetic signals relating to key host antiviral defence mechanisms,and mediators of inflammatory organ damage in *** mechanisms may be amenable to targeted treatment with existing ***-scale randomised clinical trials will be essential before any change to clinical practice.

关键词： lung drugs critical

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Biomarkers of aging

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 *** a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly *** 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 ***,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 *** 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