Age-associated alterations in pro-inflammatory gene expression in humans

National Institute On Aging

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Abstract

The goal of the first phase of GESTALT was to obtain transcriptomic, proteomic and epigenomic data from 11 purified immune cell subsets obtained from peripheral blood. Sample collection for this phase was completed in February 2020. While the last sets of samples were being collected we began to analyze RNA, protein, DNA methylation and ATAC-Seq data from the first 54 samples. During FY22 we accomplished the following: We completed and published an analysis of human immune cell-specific DNA methylation signatures and their relationships to other epigenetic marks and transcription factors. We competed an analysis of DNA methylation changes that accrue with age in human immune cell subsets. Our observations point to a role for hypoxia in inducing differential age-associated patterns of methylation. This work has been submitted for publication. We completed an analysis of DNA methylation changes that take place during differentiation of nave B and T lymphocytes to the respective memory states. We found that a proportion of memory-specific DNA methylation changes in human CD4+ T cells resulted directly from cell proliferation. This was not the case for B ells. We hypothesize that CD4+ T cell memory may simply represent an expanded pool of antigen-specific cells, whereas B cell memory formation requires additional steps of differentiation. We continued studies of chromatin accessibility changes as a function of age in human immune cell subsets. Data analysis is complete for B cells and monocytes, and ongoing for CD4+ T cells.