Effect of GWI on DNA methylation patterns and epigenetic aging in immune cells subtypes

Gulf War Illness (GWI) is a multi-symptom disorder affecting 1990–1991 Persian Gulf War veterans. Causation is not understood, and effective diagnostics and therapies have not yet been developed. Proposed risk factors for GWI include environmental exposures, genetics, as well as physiological and psychological stress acting through alterations in immune responses. In our previous PRG26 we isolated genomic DNA from peripheral blood mononuclear cells (PBMC) from GWI patients and matched sedentary healthy controls (HC) to isolate CD4+, CD8+, B and natural killer (NK) cells. We then compared telomeres’ length in these cells. Data analysis revealed that B cells of GWI patients (but not CD4+, CD8+ or NK) have shorter telomeres than the same of healthy controls. As telomere length is a widely used marker of accelerated aging, our results suggest that B cells in GWI patients are aging faster than in HC. Telomere length reflects only one dimension of biological aging. Genome-wide DNA methylation provides an independent and highly informative measure of biological age and epigenetic regulation. Importantly, epigenetic aging may parallel, diverge from, or extend beyond telomeric aging, and may reveal disease-specific regulatory changes not captured by telomere analysis alone. To date, no studies have integrated telomere biology with genome-wide DNA methylation. In the current project (PRG27), we intend to obtain preliminary results for the federal grant submission. We will analyze genomic DNA methylation in the same archived DNA samples from CD4⁺, CD8⁺, B, and NK cells that were previously studied in PRG26. This unique design enables direct comparison of telomere-based and epigenetic measures of biological aging within the same individuals and cell types. The results will provide novel, cell-specific insights into immune aging and epigenetic dysregulation in GWI and generate essential preliminary data for future federal funding. Specific Aims Aim 1: Determine whether DNA methylation based biological age corresponds to telomere length–based aging across immune cell subsets in GWI, with emphasis on B cells. Aim 2: Identify GWI-associated, cell type-specific DNA methylation patterns in CD4⁺, CD8⁺, B, and NK cells. Funded: Yes Funding source type: Nova Southeastern University