NAD+ METABOLOME OF AGED B CELLS

Abstract

The kynurenine pathway (KP) and the adenosinergic pathway (AP) contribute to the synthesis and consumption of NAD, respectively. Dysregulation of NAD levels with age is associated with impaired immune response, making the understanding of NAD metabolism vital for boosting immunity in aged populations. In this thesis, we utilized transcriptomic, proteomic, and metabolomic techniques to evaluate the NAD metabolome in aged B cells. Young B cells possess a functional KP whereas genetic signatures suggest aged B cells lose this ability. Conversely, the AP is upregulated in an age specific B cell population that is known to hinder immune response. The combined influence of reduced KP and increased AP metabolisms will likely exacerbate age related depletion of NAD and contribute to impaired immune response by B cells. Further understanding of NAD metabolism in aged B cells could suggest targeted approaches that improve NAD availability and therefore improve immune response in vulnerable populations.