| Project/Area Number |
16K16450
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Rehabilitation science/Welfare engineering
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| Research Institution | Toyohashi Sozo University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | MBNL1 / PGC-1α / apoptosis / Bax / ミトコンドリア膜電位 / アポトーシス / サルコペニア / muscleblind-like 1 / 加齢 / 骨格筋 / RNAシーケンス / 選択的スプライシング因子 / C2C12 / RNA干渉法 / Mtosin heavy chain / 老化 / 廃用性筋萎縮 / 筋線維タイプ |
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| Outline of Final Research Achievements |
The purpose of this study was to investigate a physiological role of muscleblind-like 1 (MBNL1) in aging-associated changes in mass and function of skeletal muscle. Expression level of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial membrane potential evaluated by the fluorescence ratio of JC-1 aggregate to monomer in C2C12 myotubes were suppressed by knockdown of MBNL1. On the other hand, MBNL1 knockdown-associated increase in the ratio of Bax to Bcl-2 as well as the apoptotic index in C2C12 myotubes was observed. In plantaris muscle, the expression level of MBNL1 and PGC-1α in old mice was significantly lower than that in young mice. Furthermore, the ratio of Bax to Bcl-2 in mouse plantaris muscle was increased by aging. These observations suggest that MBNL1 may be a key player of aging-associated muscle atrophy accompanied with mitochondrial dysfunction and apoptosis via mediating PGC-1α expression.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢社会にある我が国においてフレイル対策は国家的課題であるが、その病変の多様性から未だ有効策は確立されていない。ミトコンドリア機能不全やアポトーシスの増加といった骨格筋の加齢性変化がスプライシング因子によって制御されている可能性を示した本研究の成果はフレイル対抗策策定のための重要な基礎資料になるものと考えられる。
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