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 dat...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.展开更多
基金supported by the National Key Research and Development Program of China(2021YFF1201000,2022YFA1103700)the Quzhou Technology Projects(2022K46)+13 种基金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).
文摘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.
