Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humans.

Fu-Hui Xiao, Hao-Tian Wang, Long Zhao, Tian-Rui Xia, Li-Qin Yang, Si-Yu Ma, Qing-Peng Kong

Key Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Department of Pharmacology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: [email protected] Laboratory of Genetic Evolution & Animal Models (Chinese Academy of Sciences), Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Department of Pharmacology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: [email protected]. · pubmed

Paper

Abstract

Men, despite having a lower likelihood of longevity compared to women, generally exhibit better health status when they achieve longevity. The role of DNA methylation in this paradox remains unclear. We performed whole-genome bisulfite sequencing on long-lived men (LLMs), long-lived women (LLWs), younger men (YMs) and younger women (YWs) to explore specific methylation characteristics in LLMs. Despite an accelerated methylation aging rate in LLMs compared to LLWs, we identify thousands of differentially methylated genomic units (DMUs) in LLMs independent of age and sex. These DMUs, validated by an elastic net classifier, can serve as methylation markers for discriminating longevity potential in men. Many are located near health-related genes. Genes like PIWIL1 and EXT1, with promoters featuring DMUs, exemplify the potential role of LLM-specific methylation patterns in suppressing age-related diseases by regulating gene transcription. Our findings provide evidence of a distinct methylation feature contributing to healthy aging and longevity of LLMs.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper investigates DNA methylation modifications associated with male longevity, which is directly relevant to understanding the biological mechanisms of aging and longevity. It identifies specific methylation patterns that may contribute to healthy aging in long-lived men, providing insights into potential biomarkers for longevity. However, while the findings are solid and contribute to the field, they do not represent a major breakthrough or transformative work, thus warranting a moderate impact score.

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