Mikhail G Dozmorov1, Patrick Coit2, Kathleen Maksimowicz-McKinnon3, Amr H Sawalha2,4. 1. Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA. 2. Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. 3. Division of Rheumatology, Henry Ford Health System, Detroit, MI 48202, USA. 4. Center for Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
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.
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.
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