DNA methylation clocks for estimating biological age in Chinese cohorts

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-Gui Yang; Jing Qu; Feng Zhang; Peilin Jia; Guang-Hui Liu; Weiqi Zhang

doi:10.1093/procel/pwae011

DNA methylation clocks for estimating biological age in Chinese cohorts

Protein Cell. 2024 Mar 14:pwae011. doi: 10.1093/procel/pwae011. Online ahead of print.

Authors

Zikai Zheng^{1

2}, Jiaming Li^{1

2}, Tianzi Liu^{1

3}, Yanling Fan¹, Qiao-Cheng Zhai^{4

5}, Muzhao Xiong^{1

2}, Qiao-Ran Wang^{1

2}, Xiaoyan Sun^{1

2}, Qi-Wen Zheng¹, Shanshan Che^{1

2}, Beier Jiang⁴, Quan Zheng⁴, Cui Wang^{1

2}, Lixiao Liu^{1

2}, Jiale Ping^{1

2}, Si Wang^{6

7

8}, Dan-Dan Gao⁴, Jinlin Ye⁴, Kuan Yang^{1

2}, Yuesheng Zuo^{1

2}, Shuai Ma^{9

10

11

12

8}, Yun-Gui Yang^{1

2}, Jing Qu^{13

10

2

11

12

8}, Feng Zhang⁵, Peilin Jia^{1

2

14}, Guang-Hui Liu^{9

10

2

11

12

6

7

8}, Weiqi Zhang^{1

2

11

8}

Affiliations

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 The Joint Innovation Center for Engineering in Medicine, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou 324000, China.
⁵ Division of Orthopaedics, the Quzhou Affiliated 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 Institute 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.

PMID: 38482631
DOI: 10.1093/procel/pwae011

Abstract

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation at specific CpG sites. However, available DNA methylation (DNAm) age predictors are based on datasets with limited ethnic representation. Moreover, a systematic comparison between DNAm data and other omics datasets has not yet been performed. 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 (DNAm) 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 basis for evaluating aging intervention strategies.

Keywords: DNA methylation; age prediction; aging; aging clock.