| Project/Area Number |
17K09767
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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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| Research Field |
Neurology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
Ohsawa Yutaka 川崎医科大学, 医学部, 講師 (80246511)
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| Co-Investigator(Kenkyū-buntansha) |
西松 伸一郎 川崎医科大学, 医学部, 准教授 (20222185)
村上 龍文 川崎医科大学, 医学部, 准教授 (30330591)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | サルコペニア / マイオスタチン / TGF-beta / 老化 / TGF-β |
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| Outline of Final Research Achievements |
To date, the molecular mechanisms have almost been unknown leading to age-related muscular atrophy (sarcopenia), which increases the caregiver burden and shortens the healthy life expectancy. We found that the myostatin/TGF-beta signal was upregulated in skeletal muscle in aged mice. In the current study, we generated and characterized the aging mice accompanied with inhibition of myostatin activity. The mice showed amelioration of weight loss, muscle loss, reduced grip strength, and decreased muscle tension observed in the aged mice. The mice exhibited alleviation of myofiber atrophy and loss of muscle precursor satellite cell, when compared to the aged mice. In addition, inhibition of myostatin activity extended life span in the mice. We identified a myostatin/TGF-beta inhibitory molecule in skeletal muscle tissue by gene expression analysis. We are currently administring its recombinant protein to aged mice, and aim to open a breakthrough for the future treatment of sarcopenia.
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| Academic Significance and Societal Importance of the Research Achievements |
サルコペニアは介護負担を押し上げるため、その克服は先進国の先頭を切って超高齢化社会を迎えた本邦の社会的課題となっているが、保険適用を獲得している医薬品は世界的に皆無である。これまでサルコペニア研究は、骨格筋幹細胞数の減少による骨格筋再生能低下、およびtype II 線維の減少といった細胞生物学的観点が注目されてきた。本研究は、我々が独自に発見した老化マウス骨格筋のマイオスタチン/TGF-betaシグナルの亢進を端緒として、サルコペニア病態における筋線維萎縮機構を解明する分子生物学に立脚した独創性をその学術的意義とする。その阻害医薬開発は、臨床的かつ医療経済的に極めて有用と考えられる。
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