Longevity & AgingCD38 Inhibitor 78c Restores NAD+ and Cuts Inflammation in Aged Immune Cells
Aging macrophages show dramatically elevated CD38 — an enzyme that degrades NAD+ — after infection with periodontal pathogens, driving NAD+ depletion and oxidative stress. Researchers at MUSC found that treating old murine bone marrow-derived macrophages with the selective CD38 inhibitor 78c restored NAD+ levels, reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), lowered reactive oxygen species and NADPH oxidase 1, and boosted five antioxidant enzymes. Notably, the elevated CD38 in aged macrophages was not simply a product of stronger immune signaling — old cells actually showed delayed and weaker NF-κB, PI3K, and MAPK activation, yet still upregulated CD38 more than young controls, pointing to an age-specific dysregulation of NAD+ metabolism as a tractable therapeutic target in aging-related periodontitis.
