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衰老过程中的无细胞游离 DNA 甲基化模式及其与炎症相关衰老的关联。

Cell-free DNA methylation patterns in aging and their association with inflamm-aging.

机构信息

The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, 100730, PR China.

Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730, PR China.

出版信息

Epigenomics. 2024;16(10):715-731. doi: 10.1080/17501911.2024.2340958. Epub 2024 May 15.

Abstract

Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.

摘要

液体活检分析血浆中的游离 DNA(cfDNA)甲基化可提供非侵入性疾病诊断,而衰老生物标志物的研究则相对较少。本研究利用酶甲基化测序(EM-seq)技术,对来自 35 名健康个体的血液进行了 cfDNA 甲基化模式与衰老的相关性分析。结果发现了衰老特征,包括 cfDNA 水平升高和片段大小变化,以及约 2000 个与年龄相关的差异甲基化 CpG 位点。基于 48 个 CpG 位点的生物年龄预测模型与两个数据集的实际年龄具有很强的相关性。通过差异甲基化区域分析和 Olink 蛋白质组学分析揭示了与炎症相关的特定年龄的表观遗传变化。这些发现表明 cfDNA 甲基化可能是一种潜在的衰老生物标志物,并且可能会加剧老年个体的免疫炎症反应。

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本文引用的文献

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