| Project/Area Number |
22K16408
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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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) |
2022-04-01 – 2023-03-31
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| Project Status |
Discontinued (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Muscle Regenration / NAD metabolism / Muscle Stem Cell / Immune cells / Aging |
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| Outline of Research at the Start |
Aging-related decline in NAD+ is reported to impair regenerative process. CD38 is an ectoenzyme to degrade NAD+ and is reportedly increased in inflammatory macrophages during aging. In this study, I will clarify the role of CD38 in the regulation of muscle stem cell functions in aged mice. Thus, my study may provide a clue that inhibition of CD38 restore functions of aged muscle stem cell functions. Reduction in CD38 boosts NAD+ and may rescue aging- and obesity-induced delay in muscle regeneration. Metabolic reprogramming in macrophages could open new field to boost the regenerative process.
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| Outline of Annual Research Achievements |
Previous reports show macrophages-derived signals are crucial for regeneration process. Both macrophages and satellite cells require nicotinamide adenine dinucleotide (NAD+) for their biological functions. Aging-related decline in NAD+ is reported to impair regenerative process and significantly inhibits satellite cells differentiation. Administration of NAD+ precursors restore NAD+ deficiency in aged muscle and also enhances recovery process. CD38 is an ectoenzyme to degrade NAD+ and is reportedly increased in inflammatory macrophages during aging. However, how inhibition of CD38 affects satellite cells functions in aging-induced delay in recovery process, remain elusive. We are currently investigating how deletion of CD38 in aged mice affect regenerative capacity of muscle stem cells. Our initial results reveal that blocking/inhibition of CD38 results in restoration of NAD+ and muscle stem cell functions.
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