Decoding disease-specific ageing mechanisms through pathway-level epigenetic clock: insights from multi-cohort validation.

Journal: EBioMedicine
Published Date: Jul 4, 2025

Abstract

BACKGROUND: Ageing is a multifactorial process closely associated with increased risk of chronic diseases. While epigenetic clocks have advanced ageing research, most rely on isolated CpG sites, limiting biological interpretability. We developed PathwayAge, a biologically informed model that captures coordinated methylation changes at the pathway level, providing interpretable insights into ageing biology and disease mechanisms.

Authors

  • Pan Li
    Department of Infections，Beijing Hospital of Traditional Chinese Medicine, Affiliated to the Capital Medical University, No. 23, Back Road of the Art Gallery, Dongcheng District, Beijing 100010, China.
  • Jijun Zhu
    Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, No. 6, 2nd Nanjiang Road, Nansha District, 511462 Guangzhou, China.
  • Shenghan Wang
    Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, No. 6, 2nd Nanjiang Road, Nansha District, 511462 Guangzhou, China.
  • Haowen Zhuang
    Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, China.
  • Shunjie Zhang
    School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
  • Zhongting Huang
    Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, No. 6, 2nd Nanjiang Road, Nansha District, 511462 Guangzhou, China.
  • Fuqiang Cai
    School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
  • Zhijian Song
    Digital Medical Research Center, Fudan University, Shanghai, China.
  • Yuxin Liu
    School of Biomedical Engineering (Suzhou), University of Science and Technology of China, Division of Life Sciences and Medicine, Hefei, 230026, Anhui, China.
  • Weixin Liu
    School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
  • Sebastian Freidel
    Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, M7, Mannheim 68161, Germany.
  • Sijia Wang
    CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • Emanuel Schwarz
    Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. emanuel.schwarz@zi-mannheim.de.
  • Junfang Chen
    Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Baden-Württemberg, J5 68159, Germany.

Keywords

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