Age-related Differences in Monocyte DNA Methylation and Immune Function in Healthy Kenyan Adults and Children

Abstract

Background: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profi 24 les in monocytes from young adults and children from western Kenya.Results: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles.Conclusions: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

Nutritional senolytics and senomorphics: Implications to immune cells metabolism and aging – from theory to practice

“…Several immune system cells have been found to have changes in DNA methylation with aging, which affect the proliferative capacity and functionality of these cells (8). For instance, decreased DNA methylation affects the phenotypic plasticity of monocytes, the generation of TNF-α by monocytes and peripheral blood mononuclear cells (PBMCs), the cytotoxicity of NK cells, Treg formation and function, and B cell activity (81). Additionally, affecting innate and adaptive immune responses is histone modification.…”