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

Summary: 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 (...

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Main Authors: Fu-Hui Xiao, Hao-Tian Wang, Long Zhao, Tian-Rui Xia, Li-Qin Yang, Si-Yu Ma, Qing-Peng Kong
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724015092
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author Fu-Hui Xiao
Hao-Tian Wang
Long Zhao
Tian-Rui Xia
Li-Qin Yang
Si-Yu Ma
Qing-Peng Kong
author_facet Fu-Hui Xiao
Hao-Tian Wang
Long Zhao
Tian-Rui Xia
Li-Qin Yang
Si-Yu Ma
Qing-Peng Kong
author_sort Fu-Hui Xiao
collection DOAJ
description Summary: 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.
format Article
id doaj-art-4df3aa081b2e4f6c80fc6ecee1da0d50
institution Kabale University
issn 2211-1247
language English
publishDate 2025-01-01
publisher Elsevier
record_format Article
series Cell Reports
spelling doaj-art-4df3aa081b2e4f6c80fc6ecee1da0d502025-01-09T06:13:48ZengElsevierCell Reports2211-12472025-01-01441115158Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humansFu-Hui Xiao0Hao-Tian Wang1Long Zhao2Tian-Rui Xia3Li-Qin Yang4Si-Yu Ma5Qing-Peng Kong6Key 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; Corresponding authorKey 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, ChinaKey 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, ChinaKey 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, ChinaKey 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, ChinaKey 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, ChinaKey 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; CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724015092CP: Molecular biology
spellingShingle Fu-Hui Xiao
Hao-Tian Wang
Long Zhao
Tian-Rui Xia
Li-Qin Yang
Si-Yu Ma
Qing-Peng Kong
Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humans
Cell Reports
CP: Molecular biology
title Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humans
title_full Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humans
title_fullStr Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humans
title_full_unstemmed Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humans
title_short Methylome analysis in long-lived men deciphers DNA methylation modifications associated with male longevity in humans
title_sort methylome analysis in long lived men deciphers dna methylation modifications associated with male longevity in humans
topic CP: Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2211124724015092
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