Longevity & AgingCD38 Inhibitors Restore NAD+ Levels to Fight Aging and Disease
CD38 is a multifunctional enzyme that rapidly degrades NAD+, the cellular fuel critical for energy metabolism, DNA repair, and immune function. Its activity rises with age and in inflammatory or tumor environments, driving NAD+ depletion and downstream metabolic dysfunction. This comprehensive 2026 review from USC catalogs the growing arsenal of small-molecule CD38 inhibitors—spanning covalent nucleotide-based agents, NAD+ analogues, synthetic molecules, and natural products. Together these chemical strategies offer diverse routes to restore NAD+ homeostasis, improve mitochondrial and immune function, and potentially slow age-related decline or suppress tumor progression. The review lays a chemical foundation for future therapeutic development targeting this critical immunometabolic checkpoint.
