Examination of sarcopenic animal models focusing on the proteolytic system

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19720
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Hiroshima University
• Principal Investigator: Kitajima Yasuo 広島大学, 医系科学研究科(医), 助教 (70734416)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 骨格筋 / 筋再生 / タンパク分解系 / 老化 / 筋線維

Outline of Final Research Achievements

The aim of this study is to generate mice that can undergo muscle-specific proteasome dysfunction at any given time and to elucidate its effects on skeletal muscle homeostasis mechanisms. After individual maturation, skeletal muscle proteasome dysfunction in mice inhibited proteasome-mediated proteolysis, leading to muscle atrophy and reduced myofiber size. Furthermore, proteasome dysfunction was associated with necrotic cells and inflammatory cell infiltration, suggesting a link to disease. In the future, the relationship between muscle proteasome dysfunction and aging and disease should be further investigated. We expect that further elucidation of this relationship will help to elucidate one aspect of the normal homeostatic mechanism of skeletal muscle.

Free Research Field

骨格筋生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、成体骨格筋におけるプロテアソーム機能不全が筋萎縮を引き起こすことを、マウスモデルで実証した。個体成熟後の骨格筋プロテアソーム機能不全マウスでは、プロテアソームを介したタンパク質分解が阻害され、筋萎縮と筋線維のサイズの減少を引き起こした。本研究成果は、筋量を維持するためには正常なプロテアソーム機能が重要であることを示し、タンパク分解系による骨格筋研究の更なる発展につながる可能性がある。