2023 Fiscal Year Final Research Report
Development of a new treatment for sarcopenia based on the regulation of O-linked glycosylation
| Project/Area Number |
22K19754
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松島 将士 九州大学, 医学研究院, 助教 (80552869)
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| Project Period (FY) |
2022-06-30 – 2024-03-31
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| Keywords | サルコペニア / 翻訳後修飾 / O結合グリコシル化 / 健康寿命 |
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| Outline of Final Research Achievements |
Skeletal muscle atrophy (decreased skeletal muscle weight, decreased skeletal muscle cell diameter) was observed in C57BL/6J mice as they aged, and the balance between protein synthesis and protein degradation was disrupted. O-GlcNAcylation of skeletal muscle proteins tended to increase overall, but there were differences in increases and decreases depending on the molecular weight. GFAT1, a rate-limiting enzyme in the hexosamine biosynthesis pathway, was increased in skeletal muscle, and OGA, which removes O-GlcNac, was decreased. When 6-Diazo-5-oxo-L-norleucin (DON), a GFAT inhibitor, was administered to aging mice for 3 months, a decrease in skeletal muscle weight and a decrease in cell diameter were attenuated compared to the vehicle-administered group.
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| Free Research Field |
栄養学および健康科学関連
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| Academic Significance and Societal Importance of the Research Achievements |
サルコペニア患者に対する有効な予防・治療法はなく、筋力トレーニングを併用した運動療法を継続するしかないが、その効果は不十分であり、継続が困難な場合も多い。本研究では、これまで注目されていなかったO-GlcNAc化修飾に注目して、加齢における骨格筋萎縮にO-GlcNAc化修飾が重要な役割を果たしていることを明らかにした点で学術的意義が高い。骨格筋萎縮に対するO-GlcNAc化修飾制御という我々独自のパラダイムに基づく予防・治療法の基礎的基盤を築くことができれば、サルコペニアの新規予防・治療法の臨床応用の実現性は高く、健康寿命の実現に大きく寄与すると考えられ、社会的意義が大きい。
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