Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Genome Res. 2010 Apr;20(4):434-9. doi: 10.1101/gr.103101.109. Epub 2010 Mar 10.
There is a growing realization that some aging-associated phenotypes/diseases have an epigenetic basis. Here, we report the first genome-scale study of epigenomic dynamics during normal human aging. We identify aging-associated differentially methylated regions (aDMRs) in whole blood in a discovery cohort, and then replicate these aDMRs in sorted CD4(+) T-cells and CD14(+) monocytes in an independent cohort, suggesting that aDMRs occur in precursor haematopoietic cells. Further replication of the aDMRs in buccal cells, representing a tissue that originates from a different germ layer compared with blood, demonstrates that the aDMR signature is a multitissue phenomenon. Moreover, we demonstrate that aging-associated DNA hypermethylation occurs predominantly at bivalent chromatin domain promoters. This same category of promoters, associated with key developmental genes, is frequently hypermethylated in cancers and in vitro cell culture, pointing to a novel mechanistic link between aberrant hypermethylation in cancer, aging, and cell culture.
人们越来越认识到，一些与衰老相关的表型/疾病具有表观遗传基础。在这里，我们报告了人类正常衰老过程中全基因组范围的表观基因组动态的首次研究。我们在一个发现队列中鉴定了全血中与衰老相关的差异甲基化区域（aDMR），然后在一个独立的队列中在分选的 CD4(+) T 细胞和 CD14(+)单核细胞中复制这些 aDMR，表明 aDMR 发生在造血前体细胞中。在颊细胞中进一步复制 aDMR，颊细胞代表一种与血液相比起源于不同胚层的组织，证明了 aDMR 特征是多组织现象。此外，我们证明与衰老相关的 DNA 高甲基化主要发生在二价染色质结构域启动子上。同一类与关键发育基因相关的启动子，在癌症和体外细胞培养中经常发生高甲基化，这表明癌症、衰老和细胞培养中异常高甲基化之间存在新的机制联系。
