Transcriptomic analysis of peripheral blood mononuclear cells reveals age specific differences at baseline and response to acute exercise

Aging is associated with alterations in immune cell function, contributing to age-related diseases and frailty. As key drivers of the immune response, we investigated the transcriptome of peripheral blood mononuclear cells (PBMCs) using RNA-sequencing before and after high-intensity single-leg knee-extension exercise in young (Young; n=7, 23±4 years) and older individuals (Old; n=8, 65±7 years). Bioinformatic analyses revealed biological processes and pathways that were altered with aging and response to exercise. At baseline, 665 out of 19,762 genes differed in PBMCs with notable differences relating to pathways involved in DNA Damage/Telomere Stress Induced Senescence, NAD Signaling Pathway, and Oxidative Stress Induced Senescence. After exercise, 53 out of 13,695 genes were differentially expressed in the Young, while 1,026 out of 19,101 genes changed in the Old. In Young, the enriched processes and predicted pathways were linked to natural killer cells, while in Old, they focused on cell signaling immune responses. Lastly, 26 genes exhibited similar responses to exercise between groups, enriching the biological process of natural killer cell-mediated immunity regulation. Our findings indicate that PBMC gene expression is altered with aging and in response to acute exercise in older adults, with exercise having a more substantial modulating effect on the immune system response with aging. The underlying causes and functional consequences of the observed transcriptional differences require additional investigation.