PDF(Pubmed)
Abstract：
DNA methylation (DNAm) is one of the most reliable biomarkers of aging across mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, DNAm gain is less characterized. Studies have demonstrated that CpGs which gain methylation with age are enriched in Polycomb Repressive Complex 2 (PRC2) targets. However, whole-genome examination of all PRC2 targets as well as determination of the pan-tissue or tissue-specific nature of these associations is lacking. Here, we show that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells (PRC2 LMRs) gain methylation with age in all examined somatic mitotic cells. We estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the \"PRC2-AgeIndex,\" defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells which can distinguish the effect of different anti-aging interventions.
摘要：
DNA甲基化（DNAm）是哺乳动物组织衰老的最可靠的生物标志物之一。虽然DNAm的年龄依赖性全球损失已经得到了很好的表征，DNAm增益的特征较少。研究表明，随着年龄的增长而获得甲基化的CpG富含多梳抑制复合物2（PRC2）靶标。然而,缺乏对所有PRC2靶标的全基因组检查以及对这些关联的泛组织或组织特异性性质的确定.这里,我们表明，在所有检查的体细胞有丝分裂细胞中，胚胎干细胞（PRC2LMR）中与PRC2高度结合的低甲基化区域（LMR）随着年龄的增长而获得甲基化。我们估计，这种表观遗传变化代表了整个基因组中年龄依赖性DNAm增益的约90％。因此,我们提出了“PRC2-AgeIndex”，“定义为PRC2LMR中的平均DNAm，作为体细胞中细胞衰老的通用生物标志物，可以区分不同抗衰老干预措施的效果。
