Elucidation of the aging mechanism in skeletal muscle stem cells

• Project/Area Number: 18K17857
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: Kumamoto University
• Principal Investigator: Kitajima Yasuo 熊本大学, 発生医学研究所, 助教 (70734416)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Discontinued (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨格筋 / 筋再生 / 筋幹細胞 / タンパク分解系 / 老化 / タンパク分解 / サテライト細胞 / たんぱく分解系 / 骨格筋幹細胞

Outline of Final Research Achievements

In this study, we focused on the proteasome, the main proteolytic system, to elucidate its relationship to aging in muscle stem cells. Proteasome dysfunction in muscle stem cells resulted in a decrease in muscle stem cells due to an increase in the aging-related p53 protein. The p53 gene deletion in muscle stem cell-specific proteasome dysfunction mice did not rescue the number of muscle stem cells. These results suggest that there are different mechanisms for aging-related p53 in vivo and vitro.

Academic Significance and Societal Importance of the Research Achievements

筋幹細胞におけるタンパク分解系の機能不全は、老化マーカーであるp53の増加をもたらした。これにより、筋幹細胞において、タンパク分解系と老化が関係していることが示された。これらの成果は、筋幹細胞と老化をつなぐ重要な知見を提供し、今後の老化研究の発展につながる可能性がある。

Research Products

• [Journal Article] 骨格筋および骨格筋幹細胞におけるプロテアソーム機構の役割 (2020)
  • Author(s): 北嶋康雄
  • Journal Title: 基礎老化研究 Volume: 44 Pages: 39-41
  • Peer Reviewed
• [Journal Article] Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons. (2019)
  • Author(s): Akiyama T, Suzuki N, Ishikawa M, Fujimori K, Sone T, Kawada J, Funayama R, Fujishima F, Mitsuzawa S, Ikeda K, Ono H, Shijo T, Osana S, Shirota M, Nakagawa T, et al.
  • Journal Title: EBioMedicine Volume: 45 Pages: 362-378
  • DOI: 10.1016/j.ebiom.2019.06.013
  • Peer Reviewed / Open Access
• [Journal Article] Antagonizing bone morphogenetic protein 4 attenuates disease progression in a rat model of amyotrophic lateral sclerosis (2018)
  • Author(s): Shijo Tomomi、Warita Hitoshi、Suzuki Naoki、Ikeda Kensuke、Mitsuzawa Shio、Akiyama Tetsuya、Ono Hiroya、Nishiyama Ayumi、Izumi Rumiko、Kitajima Yasuo、Aoki Masashi
  • Journal Title: Experimental Neurology Volume: 307 Pages: 164-179
  • DOI: 10.1016/j.expneurol.2018.06.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Visualization of PAX7 protein dynamics in muscle satellite cells in a YFP knock-in-mouse line (2018)
  • Author(s): Kitajima Yasuo、Ono Yusuke
  • Journal Title: Skeletal Muscle Volume: 8 Issue: 1
  • DOI: 10.1186/s13395-018-0174-x
  • NAID: 120006987964
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Ubiquitin-Proteasome System Is Indispensable for the Maintenance of Muscle Stem Cells (2018)
  • Author(s): Kitajima Yasuo、Suzuki Naoki、Nunomiya Aki、Osana Shion、Yoshioka Kiyoshi、Tashiro Yoshitaka、Takahashi Ryosuke、Ono Yusuke、Aoki Masashi、Nagatomi Ryoichi
  • Journal Title: Stem Cell Reports Volume: 11 Issue: 6 Pages: 1523-1538
  • DOI: 10.1016/j.stemcr.2018.10.009
  • NAID: 120007006241
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 骨格筋幹細胞におけるプロテアソーム系の役割およびサテライト細胞研究の新たなツールと応用 (2019)
  • Author(s): 北嶋康雄
  • Organizer: 第42回日本分子生物学会
• [Presentation] ユビキチン-プロテアソーム系は筋幹細胞の恒常性維持に必須である (2019)
  • Author(s): 北嶋康雄、鈴木直輝、布宮亜樹、長名シオン、吉岡潔志、田代善崇、高橋良輔、小野悠介、青木正志、永富良一
  • Organizer: 第42回日本基礎老化学会