Elucidation of a novel cellular senescence mechanism modulated by branched-chain amino acid metabolism.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06852
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Gunma University
• Principal Investigator: Konishi Akimitsu 群馬大学, 大学院医学系研究科, 講師 (50381877)
• Co-Investigator(Kenkyū-buntansha): 大日方 英 群馬大学, 大学院医学系研究科, 准教授 (50332557)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞老化 / 分岐鎖アミノ酸 / テロメア / 活性酸素 / アミノ酸代謝 / エネルギー代謝 / DNA損傷応答

Outline of Final Research Achievements

Aging is thought to be caused, in part, by the accumulation of senescent cells in the body. In this study, we investigated the mechanisms by which metabolic abnormalities of branched-chain amino acids (BCAAs), which are essential amino acids, lead to cellular senescence. When the metabolism of BCAAs is impaired, the production of cellular energy and biomolecules is insufficient, causing cells to become senescent. We also found that when the metabolic function of BCAAs declines, oxidative stress within cells increases, accelerating cellular senescence. Furthermore, it has been shown that inhibition of BCAA metabolism in mice leads to accumulation of senescent cells and accelerated aging, and that BCAA metabolism is reduced in elderly humans. These findings suggest that the metabolic function of BCAAs is critical in suppressing aging.

Free Research Field

生化学、細胞生物学

Academic Significance and Societal Importance of the Research Achievements

日本を含め世界は超高齢化社会に入り、高齢者の健康をどのように維持していくかは重要な社会的課題となっている。分岐鎖アミノ酸は必須アミノ酸であり、高齢者での摂取量調節に関する研究が栄養学的な観点から多く行われている。しかし、分岐鎖アミノ酸代謝が細胞の老化を制御しているという報告はこれまでになく、本研究が初めてのものになる。さらに、ヒトの老化抑制にも分岐鎖アミノ酸代謝が重要であることを示した本研究から得られる知見は、高齢者の健康維持対策に貢献することが期待される。