| Project/Area Number |
20K22733
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0802:Biomedical structure and function and related fields
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| Research Institution | University of Toyama |
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Principal Investigator |
Nawaz Allah 富山大学, 学術研究部医学系, 助教 (80881482)
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Stem cell / Immune cells / Myogenesis / Pharmacology / Muscle Regenration / NAD metabolism / Muscle Stem Cell / Aging / Muscle regeneration / Myoblast / Metabolimics / Muscle Regeneration |
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| Outline of Research at the Start |
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.
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| 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.
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| 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.
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