Epigenetic mechanism of aged muscle atrophy and decreased regeneration

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K18461
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Studies on the Super-Aging Society
• Research Institution: Kyoto Prefectural University
• Principal Investigator: Kamei Yasutomi 京都府立大学, 生命環境科学研究科, 教授 (70300829)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 骨格筋 / 筋萎縮 / エピジェネティクス / サルコペニア / 加齢

Outline of Final Research Achievements

During atrophy such as aging (sarcopenia), the muscle regeneration capacity after injury is known to be decreased, which leads to impaired muscle function as well as more severe sarcopenia with lower quality of life. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Dnmt3a-KO satellite cell, important for muscle regeneration, showed suppressed myotube differentiation. Expression of Gdf5 was markedly increased in Dnmt3a-KO mice. The DNA methylation level of the Gdf5 promoter was markedly decreased in Dnmt3a-KO satellite cells, suggesting Gdf5 expression is regulated by DNA methylation. Thus, Dnmt3a appears to regulate satellite cell differentiation via DNA methylation. This mechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.

Free Research Field

分子栄養学

Academic Significance and Societal Importance of the Research Achievements

加齢により骨格筋内の遺伝子のDNAメチル化が大きく変わることが知られている。しかしながらそのメカニズムと生理的意義の詳細は不明な点が多い。本研究では、老化による骨格筋の性質変化（筋再生能低下）にDNAメチル化が関与する可能性を検証した。そして、老化に伴うDnmt3aの発現低下によって筋再生能が低下する分子機序を提示した。本研究はサルコペニアの予防改善のための分子標的同定の手がかりとなるものである。