Age-associated DNA methylation changes in naive CD4+ T cells suggest an evolving autoimmune epigenotype in aging T cells
Dozmorov MG, Coit P, Maksimowicz-McKinnon K, and Sawalha AH. Age-associated DNA methylation changes in naive CD4+ T cells suggest an evolving autoimmune epigenotype in aging T cells. Epigenomics 2017; 9(4):429-445.
AIM: We sought to define age-associated DNA methylation changes in naive CD4+ T cells.
MATERIALS & METHODS: Naive CD4+ T cells were collected from 74 healthy individuals (age 19-66 years), and age-related DNA methylation changes were characterized.
RESULTS: We identified 11,431 age-associated CpG sites, 57% of which were hypermethylated with age. Hypermethylated sites were enriched in CpG islands and repressive transcription factor binding sites, while hypomethylated sites showed T cell specific enrichment in active enhancers marked by H3K27ac and H3K4me1. Our data emphasize cancer-related DNA methylation changes with age, and also reveal age-associated hypomethylation in immune-related pathways, such as T cell receptor signaling, FCγR-mediated phagocytosis, apoptosis and the mammalian target of rapamycin signaling pathway. The MAPK signaling pathway was hypermethylated with age, consistent with a defective MAPK signaling in aging T cells.
CONCLUSION: Age-associated DNA methylation changes may alter regulatory mechanisms and signaling pathways that predispose to autoimmunity.
Medical Subject Headings
Adult; Aged; Aging; Autoimmunity; Binding Sites; CD4-Positive T-Lymphocytes; CpG Islands; DNA Methylation; Enhancer Elements, Genetic; Epigenesis, Genetic; Epigenomics; Epitopes, T-Lymphocyte; Female; Humans; Middle Aged; Promoter Regions, Genetic; Transcription Factors