2021 Fiscal Year Final Research Report
Establishment of a novel sarcopenia mouse model by reducing serum IGF1 and development of a way for sarcopenia treatment by using the model
Project/Area Number |
19K09580
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56020:Orthopedics-related
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Research Institution | Keio University |
Principal Investigator |
SATO Yuiko 慶應義塾大学, 医学部(信濃町), 研究員 (70445443)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | サルコペニア |
Outline of Final Research Achievements |
In this study, we established a novel mouse model (IGF1 conditional knockout, IGF1 cKO), in which its serum IGF1 levels were down-regulated to about half to those of control mice in adults. In IGF1 cKO mice, both muscle volume and power were significantly decreased compared with control mice, phenotypes mimic to sarcopenia patients. We found that decreased muscle volume was due to muscle atrophy in IGF1 cKO mice. In those atrophied muscles, expression levels of both anabolic and catabolic factors were decreased, suggesting that muscles underwent to metabolically a low turnover state under an IGF1 reduced condition in IGF1 cKO mice. Taken together, our results suggest that maintaining serum IGF1 levels is required to prevent sarcopenia development.
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Free Research Field |
整形外科
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Academic Significance and Societal Importance of the Research Achievements |
サルコペニアは加齢性に筋量と筋力が共に低下する退行性疾患であり、加齢を背景にした多因子疾患であると考えられていた。今回申請者はIGF1という単一の因子の血中濃度の低下のみによってサルコペニア様の表現型を若年齢のマウスにおいても発症し得る知見を得た。このことはサルコペニアの病態や発症要因を理解する上で重要な知見であり、学術的に意義がある。また、今回のモデルマウスではコントロールマウスの約半分の濃度にIGF1レベルを低下させているが、これはまさに人でも高齢者では若年者に比べて血中IGF1レベルが約1/2に低下することが知られており、本知見の人への応用という意味でも社会的意義も大きいと考えている。
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