The elucidation of a novel pathogenic progression mechanism of inflammatory muscle disease based on the senescence of mesenchymal progenitor cells.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03161
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yamanouchi Keitaro 東京大学, 大学院農学生命科学研究科(農学部), 教授 (70272440)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 筋再生 / 細胞老化 / 筋ジストロフィー / 筋前駆細胞 / 間葉系前駆細胞 / ラット

Outline of Final Research Achievements

Muscular dystrophy is a progressive muscle weakness disorder, with Duchenne muscular dystrophy (DMD) being particularly severe and fatal. Consequently, the development of effective treatments is of paramount importance. While the widely used DMD model, the mdx mouse, exhibits mild symptoms, we have developed a DMD rat model that faithfully reproduces the severe symptoms of human DMD. In the skeletal muscles of these DMD rats, we observed the expression of the cellular senescence marker p16, suggesting that senescent cells may play a role in disease progression. Inhibiting the emergence of senescent cells through p16 knockout or administering the senolytic drug ABT263 improved muscle strength and mitigated weight loss, fibrosis, and adipogenesis in DMD rats. Furthermore, we observed that the tongue muscles of DMD rats exhibited resistance to dystrophin deficiency, with minimal muscle fiber necrosis or regeneration.

Free Research Field

筋再生学

Academic Significance and Societal Importance of the Research Achievements

難治性の遺伝性疾患であるデュシェンヌ型筋ジストロフィー（DMD）の治療法としてはこれまで遺伝子治療、細胞移植治療の開発に主眼が置かれてきた。本研究成果により、これらに加えて老化細胞を標的とした新たな治療法開発の蓋然性が提示された。また、老化細胞を標的とした治療法開発はDMDにとどまらず、他の炎症性疾患へも敷衍できる可能性を秘めている。