Elucidation of Muscle Aging using Random Mutagenesis

Research Project

Project/Area Number	18K09089
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56020:Orthopedics-related
Research Institution	National Center for Geriatrics and Gerontology
Principal Investigator	Hosoyama Tohru 国立研究開発法人国立長寿医療研究センター, 再生再建医学研究部, 室長 (20638803)
Co-Investigator(Kenkyū-buntansha)	松井康素国立研究開発法人国立長寿医療研究センター, ロコモフレイルセンター, センター長 (50501623)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	骨格筋幹細胞 / 幹細胞老化 / スリーピングビューティーシステム / マウスiPS細胞 / 骨格筋老化 / トランスポゾン / Creドライバーマウス / 変異挿入
Outline of Final Research Achievements	In recent years, it has been shown the possibility that skeletal muscle stem cells, which play an important role in maintaining skeletal muscle homeostasis, are aged with aging, and their association with sarcopenia has been pointed out. The purpose of this study was to clarify the molecular mechanism of muscle stem cell aging using the Sleeping Beauty System (SB), which can insert random mutations into the genome. We developed induced pluripotent stem (iPS) cells in which SB was introduced specifically for muscle stem cells, and searched for aging-related genes after inducing differentiation of muscle stem cells. As a result, we have not been able to identify the genes involved in stem cell aging, but the technique of mutating stem cells using SB is applicable to various cell types and is expected to be widely used in the future.
Academic Significance and Societal Importance of the Research Achievements	サルコペニアへの対応は、超高齢社会に突入した我が国において早急に解決すべき喫緊の課題である。本研究では、サルコペニアとの関連性が指摘されている骨格筋幹細胞老化の分子機構を明らかにすることに、幹細胞ゲノム特異的に変異を挿入するというこれまでにない方法を用いて挑戦した。残念ながら本研究では、骨格筋幹細胞の老化に関わる因子の同定には至らなかったが、本システムの汎用性は高く、骨格筋老化のみならず様々な細胞種の老化現象を明らかにする上で今後有効な手段となり得る。