Identification of age-related mitochondrial protein in specific organs

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K11525
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: FUJITA Yasunori 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (30515888)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 老化 / ミトコンドリア

Outline of Final Research Achievements

Mitochondrial dysfunction has been considered to be one of the hallmarks of aging. However, organ-specific alteration of mitochondria during the aging process remains to be elucidated. In this study, we tried to identify mitochondrial proteins whose expressions were organ-specifically altered during the aging process. First, based on omics data in human fetal lung-derived fibroblasts, we selected several mitochondrial proteins whose expressions were increased or decreased in senescent cells compared with proliferating cells. Second, we investigated gene expression levels of those proteins in young and aged mice, founding that mitochondrial protein X was decreased only in the kidney from aged mice compared with that from young mice. In addition, the expression levels of mitochondrial protein X were negatively correlated to those of p21, implying that mitochondrial protein X may be involved in cellular senescence observed in aged kidney.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、ミトコンドリアタンパク質Xが加齢に伴い腎臓特異的に発現低下を示すことが明らかとなった。また、呼吸鎖障害による活性酸素種の増加が細胞老化の早期プロセスに関与しない可能性を見出した。これは、細胞老化とミトコンドリア機能異常の関係の再考を促す重要な知見であり、今後のさらなる検証が望まれる。また、ミトコンドリアタンパク質Xについては、加齢に伴うミトコンドリアの変質が臓器により異なることを示唆するものである。今後、ミトコンドリアタンパク質Xの機能・役割、老化との因果関係を明らかにすることで、臓器老化のメカニズムの一端を解明できるものと考えられる。