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

IF 7.5 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-07 DOI:10.1016/j.celrep.2024.115158

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

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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.

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对长寿男性的甲基化分析揭示了与人类男性寿命相关的DNA甲基化修饰。

尽管男性长寿的可能性低于女性，但当他们长寿时，通常表现出更好的健康状况。DNA甲基化在这一悖论中的作用尚不清楚。我们对长寿男性（LLMs）、长寿女性（LLWs）、年轻男性（YMs）和年轻女性（YWs）进行了全基因组亚硫酸盐测序，以探索长寿男性（LLMs）中特定的甲基化特征。尽管与llw相比，llm的甲基化老化速度加快，但我们在llm中发现了数千个独立于年龄和性别的差异甲基化基因组单位（dmu）。这些dmu通过弹性网络分类器验证，可以作为区分男性长寿潜力的甲基化标记。其中许多位于与健康相关的基因附近。PIWIL1和EXT1等启动子具有dmu特征的基因，证明了llm特异性甲基化模式通过调节基因转录在抑制年龄相关疾病中的潜在作用。我们的研究结果提供了明显的甲基化特征有助于llm的健康衰老和长寿的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.