Abstract
CD38 is a transmembrane protein expressed in immune and non-immune cells involved in nicotinamide adenine dinucleotide (NAD+) consumption, cyclic Adenosine Diphosphate Ribose (cADPR) generation, and calcium mobilization by its enzymatic activity. It also promotes an activated and pro-inflammatory phenotype in immune cells. Senescence is a cellular state of cell growth arrest accompanied by senescent-associated secretory phenotype (SASP) products. In aging, there is an accumulation of senescent cells and higher concentrations of proinflammatory molecules, showing the relationship between aging, senescence, and inflammaging, which potentially contributes to immunosenescence and exhaustion in aging. Given that aging involves the overexpression of CD38, which leads to metabolic alterations due to NAD+ depletion and promotes the over-representation and activation of proinflammatory immune phenotypes, studies are focusing on elucidating the potential contributions of CD38 activity. Some studies suggest that CD38's increased expression in aging is supported by SASP, which creates a vicious circle between senescence and low-grade inflammation in aging. Here, we recapitulate the evidence showing the role of CD38 in innate and non-immune cells in aging and inflammaging. We also highlight the importance of CD38 in T cell function, emphasizing the potential contribution of this protein to the effects of inflammaging on T cell composition and exhaustion. Additionally, we propose new approaches to evaluate effector, memory, and regulatory T cells (Tregs) in aging in a CD38-dependent manner.
Keywords
CD38, T lymphocytes, Inflammation, Inflammaging, Immunosenescence, Aging, Immune exhaustion