DNA methylation clocks for estimating biological age in Chinese cohorts  

作　　者：Zikai Zheng Jiaming Li Tianzi Liu Yanling Fan Qiao-Cheng Zhai Muzhao Xiong Qiao-Ran Wang Xiaoyan Sun Qi-Wen Zheng Shanshan Che Beier jiang Quan Zheng Cui Wang Lixiao Liu Jiale Ping Si Wang Dan-Dan Gao Jinlin Ye Kuan Yang Yuesheng Zuo Shuai Ma Yun-GuiYang Jig Qu Feng Zhang Peilin Jia Guang-Hui Liu Weiqi Zhang 

机构地区：[1]CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]CAS Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences,Shanghai 200031,China [4]Division of Orthopaedics,Quzhou Affliated Hospital of Wenzhou Medical University,Quzhou 324000,China [5]The Joint Innovation Center for Engineering in Medicine,Quzhou Affliated Hospital of Wenzhou Medical University,Quzhou 324000,China [6]Advanced Innovation Center for Human Brain Protection,and National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China [7]Aging Translational Medicine Center,International Center for Aging and Cancer,Xuanwu Hospital,Capital Medical University,Beijing 100053,China [8]Aging Biomarker Consortium,Beijing 100101,China [9]State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [10]Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [11]nstitute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China [12]Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China [13]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [14]National Genomics Data Center,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China

出　　处：《Protein & Cell》2024年第8期575-593,共19页蛋白质与细胞（英文版）

基　　金：supported by the National Key Research and Development Program of China(2021YFF1201000,2022YFA1103700);the Quzhou Technology Projects(2022K46);the National Natural Science Foundation of China(Grant Nos.32121001,81921006,82125011,92149301,82361148131,82192863);the National Key Research and Development Program of China(2020YFA0804000,2020YFA0112200,the STI2030-Major Projects-2021ZD0202400,2021YFA1101000);the National Natural Science Foundation of China(Grant Nos.92168201,92049304,92049116,82122024,82071588,32000510,8236114813082271600,82322025,82330044,32341001);CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38010400);the Science and Technology Service Network Initiative of Chinese Academy of Sciences(KFJSTS-QYZD-2021-08-001);the Beijing Natural Science Foundation(Z230011,5242024)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101);New Cormerstone Science Foundation through the XPLORER PRIZE(2021-1045);YouthInnovation Promotion Association of CAS(E1CAZW0401,2022083);Excellent Young Talents Program of Capital Medical University(12300927);the Project for Technology Development of Beijing-affliated Medical ResearchInstitutes(11000023T000002036310);ExcellentYoung Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105);Young Elite Scientists Sponsorship Program by CAST(2021QNRC001);Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY202X-X).

摘　　要：Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG sites.However,a systematic comparison between DNA methylation data and other omics datasets has not yet been performed.Moreover,available DNAm age predictors are based on datasets with limited ethnic representation.To address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm changes.Additionally,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological age.The clocks were further employed to predict factors influencing aging rates.The DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age assessment.Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.

关 键 词：DNA methylation aging clock AGING age prediction 

分 类 号：R596[医药卫生—内科学]