Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes

• Published in: Scientific reports Vol. 5; no. 1; p. 13107
• Main Authors: Tserel, Liina, Kolde, Raivo, Limbach, Maia, Tretyakov, Konstantin, Kasela, Silva, Kisand, Kai, Saare, Mario, Vilo, Jaak, Metspalu, Andres, Milani, Lili, Peterson, Pärt
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 19.08.2015
• Subjects: Adult; Age; Aged; Aged, 80 and over; Aging - genetics; CCR7 protein; CD27 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation - genetics; Cell Lineage - genetics; CpG islands; CpG Islands - genetics; DNA fingerprinting; DNA methylation; DNA Methylation - genetics; Gene expression; Gene Expression Regulation; Histone Code - genetics; Humans; Immunity - genetics; Immunocompetence; Lymphocytes; Lymphocytes T; Middle Aged; Runx3 protein; Transcription; Transcription, Genetic; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep13107

Human ageing affects the immune system resulting in an overall decline in immunocompetence. Although all immune cells are affected during aging, the functional capacity of T cells is most influenced and is linked to decreased responsiveness to infections and impaired differentiation. We studied age-related changes in DNA methylation and gene expression in CD4+ and CD8+ T cells from younger and older individuals. We observed marked difference between T cell subsets, with increased number of methylation changes and higher methylome variation in CD8+ T cells with age. The majority of age-related hypermethylated sites were located at CpG islands of silent genes and enriched for repressive histone marks. Specifically, in CD8+ T cell subset we identified strong inverse correlation between methylation and expression levels in genes associated with T cell mediated immune response (LGALS1, IFNG, CCL5, GZMH, CCR7, CD27 and CD248) and differentiation (SATB1, TCF7, BCL11B and RUNX3). Our results thus suggest the link between age-related epigenetic changes and impaired T cell function.