Whole-genome methylation analysis of aging human tissues identifies age-related changes in developmental and neurological pathways

对衰老人体组织的全基因组甲基化分析可识别与年龄相关的发育和神经通路变化

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作者:Ravi Tharakan, Ceereena Ubaida-Mohien, Christopher Dunn, Mary Kaileh, Rakel Tryggvadottir, Linda Zukley, Chee W Chia, Ranjan Sen, Luigi Ferrucci

Abstract

Age-associated changes in the DNA methylation state can be used to assess the pace of aging. However, it is not understood what mechanisms drive these changes and whether these changes affect the development of aging phenotypes and the aging process in general. This study was aimed at gaining a more comprehensive understanding of aging-related methylation changes across the whole genome, and relating these changes to biological functions. It has been shown that skeletal muscle and blood monocytes undergo typical changes with aging. Using whole-genome bisulfite sequencing, we sought to characterize the genome-wide changes in methylation of DNA derived from both skeletal muscle and blood monocytes, and link these changes to specific genes and pathways through enrichment analysis. We found that methylation changes occur with aging at the locations enriched for developmental and neuronal pathways regulated in these two peripheral tissues. These results contribute to our understanding of changes in epigenome in human aging.

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