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Nat Commun. 2014 Nov 18;5:5366. doi: 10.1038/ncomms6366.

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

Author information

1
Departments of Epidemiology & Prevention, and Biostatistics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
2
Department of Gerontology and Geriatric Medicine, J. Paul Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
3
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
4
Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington 98115, USA.
5
Departments of Pathology and Cardiology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
6
Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, New York 10032, USA.
7
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55454, USA.
8
Molecular Biology, Nijmegen Centre for Molecular Life Sciences (NCMLS), Nijmegen 6525 GA Netherlands.
9
Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia 24061, USA.
10
Department of Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
11
Department of Pathology, University of Vermont, Colchester, Vermont 05446, USA.
#
Contributed equally

Abstract

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.

PMID:
25404168
PMCID:
PMC4280798
DOI:
10.1038/ncomms6366
[Indexed for MEDLINE]
Free PMC Article

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