» Articles » PMID: 25404168

Age-related Variations in the Methylome Associated with Gene Expression in Human Monocytes and T Cells

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.

Citing Articles

Interpretable deep learning of single-cell and epigenetic data reveals novel molecular insights in aging.

Li Z, Du Z, Huang D, Teschendorff A Sci Rep. 2025; 15(1):5048.

PMID: 39934290 PMC: 11814351. DOI: 10.1038/s41598-025-89646-1.


Structural and functional brain correlates of the neutrophil- and monocyte-to-lymphocyte ratio in neuropsychiatric disorders.

McIntosh R Brain Behav Immun Health. 2025; 43:100940.

PMID: 39877850 PMC: 11773257. DOI: 10.1016/j.bbih.2024.100940.


Epigenetic ageing clocks: statistical methods and emerging computational challenges.

Teschendorff A, Horvath S Nat Rev Genet. 2025; .

PMID: 39806006 DOI: 10.1038/s41576-024-00807-w.


Trends of genetic contributions on epigenetic clocks and related methylation sites with aging: A population-based adult twin study.

Hong X, Cao H, Cao W, Lv J, Yu C, Huang T Aging Cell. 2024; 24(3):e14403.

PMID: 39543924 PMC: 11896513. DOI: 10.1111/acel.14403.


Expression of most retrotransposons in human blood correlates with biological aging.

Tsai Y, Seymen N, Thompson I, Zou X, Mumtaz W, Gerlevik S Elife. 2024; 13.

PMID: 39417397 PMC: 11486490. DOI: 10.7554/eLife.96575.


References
1.
Zardo G, Ciolfi A, Vian L, Starnes L, Billi M, Racanicchi S . Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression. Blood. 2012; 119(17):4034-46. DOI: 10.1182/blood-2011-08-371344. View

2.
Ong M, Holbrook J . Novel region discovery method for Infinium 450K DNA methylation data reveals changes associated with aging in muscle and neuronal pathways. Aging Cell. 2013; 13(1):142-55. PMC: 4326857. DOI: 10.1111/acel.12159. View

3.
Bell J, Tsai P, Yang T, Pidsley R, Nisbet J, Glass D . Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 2012; 8(4):e1002629. PMC: 3330116. DOI: 10.1371/journal.pgen.1002629. View

4.
Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

5.
Karolchik D, Barber G, Casper J, Clawson H, Cline M, Diekhans M . The UCSC Genome Browser database: 2014 update. Nucleic Acids Res. 2013; 42(Database issue):D764-70. PMC: 3964947. DOI: 10.1093/nar/gkt1168. View