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A single-nucleus transcriptomic atlas of primate testicular Aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis

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Protein & Cell 2023年第12期14卷 888-907页

作者： Daoyuan Huang Yuesheng Zuo Chen Zhang Guoqiang Sun Ying Jing Jinghui Lei Shuai Ma Shuhui Sun Huifen Lu Yusheng Cai Weiqi Zhang Fei Gao Andy Peng Xiang Juan Carlos Izpisua Belmonte Guang-Hui Liu Jing Qu Si Wang Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China 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 Institute for Stemcell and Regeneration CAsBeijing100101China China National Center for Bioinformation Beijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China 11Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Center for Stem Cell Biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue EngineeringMinistry of EducationSun Yat-sen UniversityGuangzhou510000China Department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510000China Altos Labs Inc.San DiegoCA 92121USA and Aging Biomarker Consortium China

The testis is pivotal for male reproduction,and its progressive functional decline in Aging is associated with infertility.However,the regulatory mechanism underlying primate testicular Aging remains largely elusive.Here,we resolve the Aging-related cellular and molecular alterations of primate testicular Aging by establishing a single-nucleus transcriptomic atlas.Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir,disturbed meiosis and impaired spermiogenesis along the sequential continuum.Remarkably,Sertoli cell was identified as the cell type most susceptible to Aging,given its deeply perturbed age-associated transcriptional profiles.Concomitantly,downregulation of the transcription factor Wilms'Tumor 1(WTi),essential for Sertoli cell homeostasis,was associated with accelerated cellular senescence,disrupted tight junctions,and a compromised cell identity signature,which altogether may help create a hostile microenvironment for spermatogenesis.Collectively,our study depicts in-depth transcriptomic traits of non-human primate(NHP)testicular Aging at single-cell resolution,providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular Aging and age-related male reproductive diseases.

关键词： single-nucleus RNA sequencing primate testis Aging WT1

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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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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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The ionome and proteome landscape of Aging in laying hens and relation to egg white quality

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中国科学:生命科学英文版 2023年第9期66卷 2020-2040页

作者： Guang Li Yuqing Feng Jian Cui Qihang Hou Tanfang Li Meiting Jia Zhengtian lv Qiuyu Jiang Ying Wang Ming Zhang Lin Wang Zengpeng Lv Junyou Li Yuming Guo Bingkun Zhang State Key Laboratory of Animal Nutrition and Feeding China Agricultural UniversityBeijing 100193China Sichuan Tieqilishi Industrial Co. Ltd.Mianyang 621010China Sichuan Sundaily Farm Ecological Food Co. Ltd.Mianyang 621010China Graduate School of Agricultural and Life Sciences The University of TokyoIbaraki 319-0206Japan

The ionome is essential for maintaining body function and health status by participating in diverse key biological processes.Nevertheless, the distribution and utilization of ionome among different organs and how Aging impacts the ionome leading to a decline in egg white quality remain unknown. Thus, we used inductively coupled plasma mass spectrometry(ICP-MS) to analyze 35 elements and their isotopic contents in eight organs of laying hens at 35, 72, and 100 weeks. Moreover, the magnum proteome, amino acids in egg white, and egg white quality were analyzed in laying hens at three different ages using 4D proteomics techniques, an amino acid analyzer, and an egg quality analyzer. Across the organs, we identified varying distribution patterns among macroelements(Mg24, Ca43/44, K39, and P31), transition metals(Zn64/66, Cu63/65, Fe56/57, and Mn55), and toxic elements(Pb208, Ba137, and Sr86). We observed an organ-specific Aging pattern characterized by the accumulation of toxic elements(Pb208, Ba137, and Sr86) and calcification in the small intestine. Additionally, a decrease in the utilization of essential trace elements selenium(Se78/82) and manganese(Mn55) was noted in the oviduct. By analyzing ionome in tandem with egg quality, egg white amino acids, and proteome, we unveiled that the reduction of selenium and manganese concentrations in the magnum during the Aging process affected amino acid metabolism, particularly tryptophan metabolism, thereby inhibiting the amino acid synthesis in the magnum. Furthermore, it accelerated the senescence of magnum cells through necroptosis activation, leading to a decline in the albumen secretion function of the magnum and subsequently reducing egg white quality.Overall, this study provides insights into the evolution of 35 elements and their isotopes across 8 organs of laying hens with age.It also reveals the elemental composition, interactions, and utilization patterns of these organs, as well as their correlation with egg white quality. The present study highlights the signif

关键词： Aging elements ionome isotopes laying hens proteome

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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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Analyzing the cellular and molecular atlas of ovarian mesenchymal cells provides a strategy against female reproductive Aging

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Science China(Life Sciences) 2023年第12期66卷 2818-2836页

作者： Longzhong Jia Wenji Wang Jing Liang Shudong Niu Yibo Wang Jian Yang Lingyu Li Ge Wang Xueqiang Xu Lu Mu Kaixin Cheng Xuebing Yang Yijing Wang Haoshu Luo Guoliang Xia Yuwen Ke Yan Zhang Hua Zhang State Key Laboratory of Animal Biotech Breeding College of Biological SciencesChina Agricultural UniversityBeijing 100193China School of Life Sciences Taizhou UniversityTaizhou 318000China National Institute of Biological Sciences Beijing 102206China Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China College of Life ScienceNingxia UniversityYinchuan 750021China

Ovarian mesenchymal cells(oMCs)constitute a distinct microenvironment that supports folliculogenesis under physiological conditions.Supplementation of exogenous non-ovarian mesenchymal-related cells has been reported to be an efficient approach to improve ovarian functions.However,the development and cellular and molecular characteristics of endogenous oMCs remain largely unexplored.In this study,we surveyed the single-cell transcriptomic landscape to dissect the cellular and molecular changes associated with the Aging of oMCs in mice.Our results showed that the oMCs were composed of five ovarian differentiatedMC(odMC)populations and one ovarian mesenchymal progenitor(oMP)cell population.These cells could differentiate into various odMCs via an oMP-derived route to construct the ovarian stroma structures.Comparative analysis revealed that ovarian Aging was associated with decreased quantity of oMP cells and reduced quality of odMCs.Based on the findings of bioinformatics analysis,we designed different strategies involving supplementation with young oMCs to examine their effects on female fertility and health.Our functional investigations revealed that oMCs supplementation prior to ovarian senescence was the optimal method to improve female fertility and extend the reproductive lifespan of aged females in the longterm.

关键词： single-cell analysis ovary mesenchyma mesenchymal progenitor cells Aging infertility

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Epigenetic regulation of mesenchymal stem cell Aging through histone modifications

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Genes & Diseases 2023年第6期10卷 2443-2456页

作者： Yanping Sun Haoyu Zhang Tao Qiu Li Liao Xiaoxia Su State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Pediatrics&Engineering Research Center of Oral Translational Medicine Ministry of EducationWest China Hospital of StomatologySichuan UniversityChengduSichuan 610041China

Stem cell senescence and exhaustion,a hallmark of Aging,lead to declines in tissue repair and regeneration in aged individuals.Emerging evidence has revealed that epigenetic regulation plays critical roles in the self-renew,lineage-commitment,survival,and function of stem cells.Moreover,epigenetic alterations are considered important drivers of stem cell dysfunction during Aging.In this review,we focused on current knowledge of the histone modifications in the Aging of mesenchymal stem cells(MSCs).The aberrant epigenetic modifications on histones,including methylation and acetylation,have been found in Aging MSCs.By disturbing the expression of specific genes,these epigenetic modifications affect the self-renew,survival,and differentiation of MSCs.A set of epigenetic enzymes that write or erase these modifications are critical in regulating the Aging of MSCs.Furthermore,we discussed the rejuvenation strategies based on epigenetics to prevent stem cell Aging and/or rejuvenate senescent MSCs.

关键词： Aging Epigenetic Histone acetylation Histone methylation Mesenchymal stem cell

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Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

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Protein & Cell 2022年第6期13卷 422-445页

作者： He Li Lei Zhu Rong Wang Lihui Xie Jie Ren Shuai Ma Weiqi Zhang Xiuxing Liu Zhaohao Huang Binyao Chen Zhaohuai Li Huyi Feng Guang-Hui Liu Si Wang Jing Qu Wenru Su State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-Sen UniversityGuangzhou 510060China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerXuanwu HospitalCapital Medical UniversityBeijing 100053China China National Center for Bioinformation Beijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Chongqing Renji Hospital University of Chinese Academy of SciencesChongqing 400062China

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure.Lymph nodes,which filter the lymph to identify and fight infections,play a central role in this process.However,careful characterization of the impact of Aging on lymph nodes and associated autoimmune diseases is lacking.We combined single-cell RNA sequencing(scRNA-seq)with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes(CDLNs)of both young and old mice with or without experimental autoimmune uveitis(EAU).We found extensive and complicated changes in the cellular constituents of CDLNs during Aging.When confronted with autoimmune challenges,old mice developed milder EAU compared to young mice.Within this EAU process,we highlighted that the pathogenicity of T helper 17 cells(Th17)was dampened,as shown by reduced GM-CSF secretion in old mice.The mitigated secretion of GMCSF contributed to alleviation of IL-23 secretion by antigen-presenting cells(APCs)and may,in turn,weaken APCs’effects on facilitating the pathogenicity of Th17 cells.Meanwhile,our study further unveiled that Aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs.Overall,Aging altered immune cell responses,especially through toning down Th17 cells,counteracting EAU challenge in old mice.

关键词： Aging experimental autoimmune uveitis Th17 cell APCs single-cell sequencing

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