CD38 Causes Age-Related NAD+ Loss and Mitochondrial Dysfunction: Preclinical Findings
Synopsis
NAD+ levels decrease with aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD+ has not been elucidated. This study shows that the enzyme CD38, which breaks down NAD+, increases with age and causes this NAD+ loss. CD38 also leads to mitochondrial dysfunction partly by affecting SIRT3, a key mitochondrial protein. Additionally, CD38 degrades nicotinamide mononucleotide (NMN), a molecule used in NAD-boosting therapies. This identifies CD38 as a major regulator of NAD+ levels and a factor influencing NAD+ replacement treatments for aging and metabolic diseases.
Journal
Cell Metabolism