| Project/Area Number |
18K11067
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | National Center of Neurology and Psychiatry (2019-2020)
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2018) |
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Principal Investigator |
Motohashi Norio 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 室長 (50532727)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 骨格筋 / 筋線維タイプ / 筋代謝 / 老化 / 筋萎縮 / 筋幹細胞 / 筋疾患 / 加齢 / 萎縮 / 代謝 |
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| Outline of Final Research Achievements |
Skeletal muscles are composed of two types of muscle fibers, and these fibers can be switched between fast and slow under several circumstances. However, it is unclear how muscle fiber type transitions are regulated. In this study, we have developed transgenic mice, which allow distinguishing each muscle fiber type by fluorescent proteins. Using cultured myotubes derived from these mice, we have identified several factors that could influence slow-to-fast or fast-to-slow fiber type transition. One of them, CCL19, C-C motif chemokine ligand 19, could induce fast-to-slow type fiber transition and reduced the basal respiration in vitro, and the phenotypes were validated in vivo. Additionally, several experiments using knockout mice have revealed that muscle fiber transition induced by CCL19 was mediated through Rgs4-Sirt1 signaling pathway. Our results were proposed the novel pathway that induced muscle fiber type transitions.
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| Academic Significance and Societal Importance of the Research Achievements |
日本は長寿大国である一方, 平均寿命と健康寿命の間に10年の隔たりがあるため, 世界屈指の「寝たきり」大国と呼ばれる. 骨格筋は運動や身体活動に必須であり, 代謝性臓器としても機能している事から, 健康的な骨格筋維持が健康寿命延伸の鍵となる. 本研究で同定した筋線維タイプ変換誘導因子は筋代謝制御に関与し, 加齢や寝たきりによる筋萎縮の原因解明に直結すると考えられる為, 予防・治療法開発に繋がる科学的根拠を提供すると考えられる. 本研究で得られた成果は, 分子生物学のみならず, 老年医学・リハビリテーション医学及び健康科学など多方面の研究分野において発展可能性があり, 大きな意義があると考える.
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