2021 Fiscal Year Annual Research Report
Role of CD38 and NAD+ metabolism in macrophages during recovery of muscle after injury in aged mice
| Project/Area Number |
20K22733
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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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| Keywords | Muscle Regenration / NAD metabolism / Muscle Stem Cell / Immune cells / Aging |
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| Outline of Annual Research Achievements |
Aging is reported to delay the recovery process from muscle injury. NAD+ is a key molecule regulating energy metabolism in mitochondria, and age-related loss of NAD+ also delayed the recovery of muscle after injury. 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 inhibit satellite cells differentiation into myoblast (Zhang et al., Science 2016). CD38 is an enzyme to degrade NAD+ and its increased expression during aging results in reduction of NAD+ levels. Thus, I hypothesize that inhibition of CD38 in M1 macrophages are important to maintain NAD+ levels and improve muscle recovery process. I utilized CD38 KO mice and performed recovery analysis. I found that blockage of CD38 boosts skeletal muscle regeneration in aged mice. I also found that inhibition of CD38 enhances muscle stem/satellite cells differentiation. Both in vivo and in vitro study revealed that genetic blockage of CD38 confers positive impact on muscle recovery process.
Our in vitro study confirmed that induction of inflammatory macrophage by lipopolysaccharide (LPS) in bone marrow-derived macrophages (BMDM) induces expression of CD38, indicating that CD38 is exclusively expressed in inflammatory macrophages. Higher expression of CD38 reduces levels of NAD+ in cultured BMDM. Metabolic reprogramming in immune cells or muscle stem cells could open new field to boost the regenerative process.
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[Journal Article] Astaxanthin, a Marine Carotenoid, Maintains the Tolerance and Integrity of Adipose Tissue and Contributes to Its Healthy Functions2021
Author(s)
1.Nawaz A, Nishida Y, Takikawa A, Fujisaka S, Kado T, Aminuddin A, Bilal M, Jeelani I, Aslam MR, Nishimura A, Kuwano T, Watanabe Y, Igarashi Y, Okabe K, Ahmed S, Manzoor A, Usui I, Yagi K, Nakagawa T, Tobe K.
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Journal Title
Nutrients
Volume: 13
Pages: 4374～4374
DOI
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