Role of CD38 and NAD+ metabolism in macrophages during recovery of muscle after injury in aged mice

In this study, I try to elucidate the role of CD38 NAD consuming enzyme and NAD+ metabolism during aging using CD38 knockout mice and metabolomics analysis. I facilitate the metabolomics approach to reveal the metabolic reprogramming in immune cells during muscle regeneration in aged CD38 KO mice.

CD38 is NAD+ consuming enzyme that degrade NAD+ and its expression decreases with aging. CD38 is reported to contribute to the aging-related sterile inflammation and impairs systemic insulin sensitivity in aged mice. In addition, aging-induced decline in NAD+ impair skeletal muscle regeneration by inhibiting muscle stem/satellite cells differentiation into myoblast and myofibers. Therefore, we hypothesized that that inhibition of CD38 would improve the skeletal muscle repair process through maintenance of NAD + levels. In this study, we found that administration of 78c (CD38 inhibitor) enhances NAD+ levels in C2C12 myoblast and also improve differentiation of myoblasts. Further, deletion of CD38 in aged mice enhances muscle stem/satellite cells differentiation and promotes myogenesis. Taken together, we show that inhibition of CD38 improves muscle stem cell functions and ameliorates aging-related decline in muscle recovery/regeneration.

Clinical importance of inhibition of CD38 may serve as best therapeutic tool for patients suffering from muscle wasting disorder and age-related muscle disorders. Metabolic reprogramming in immune cells or muscle stem cells could open a new field to boost the regenerative process.