Age-related variations in the methylome associated with gene expression in human monocytes and T cells

Lindsay M. Reynolds, Jackson R. Taylor, Jingzhong Ding, Kurt Lohman, Craig Johnson, David Siscovick, Gregory Burke, Wendy Post, Steven Shea, David R. Jacobs, Hendrik Stunnenberg, Stephen B. Kritchevsky, Ina Hoeschele, Charles E. McCall, David M. Herrington, Russell P. Tracy, Yongmei Liu

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112 Scopus citations


Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age- and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process.

Original languageEnglish (US)
Article number5366
JournalNature communications
StatePublished - 2014

Bibliographical note

Funding Information:
This research was supported by contracts N01-HC-from the National Heart, Lung and Blood Institute, by grants UL1-RR-024156 and UL1-RR-025005 from the National Center for Research Resources, and T32AG033534 from the National Institute of Aging. The MESA Epigenomics & Transcriptomics Study was funded by NHLBI grant R01HL101250 to Wake Forest University Health Sciences. We thank the other investigators, the staff and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at

Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.


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