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

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22733
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: University of Toyama
• Principal Investigator: Nawaz Allah 富山大学, 学術研究部医学系, 助教 (80881482)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: Stem cell / Immune cells / Myogenesis / Pharmacology

Outline of Final Research Achievements

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.

Free Research Field

Pharmacology

Academic Significance and Societal Importance of the Research Achievements

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.