Analysis of metabolic pathways that control organismal aging using the short-lived vertebrate model.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K15701
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Osaka University
• Principal Investigator: Abe Kota 大阪大学, 微生物病研究所, 特任助教(常勤) (10867279)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 老化 / 寿命 / 代謝 / ターコイズキリフィッシュ

Outline of Final Research Achievements

By using an ultra-short-lived model vertebrate, turquoise killifish, I explored metabolic pathways that control organismal aging in vertebrates. I performed comparative metabolomics and genomics between two strains of turquoise killifish; the lifespan of longer-lived strain has twice longer than that of shorter-lived strain. Then, by genomic and pharmacological analysis, I found that an intermediate metabolite of kynurenine pathway, a metabolic pathway of tryptophan, has anti-aging properties in various tissues. Also, I found that a loss-of-function of a ceramidase functioning in the intestine leads to the anti-aging effects to the whole body.

Free Research Field

老化

Academic Significance and Societal Importance of the Research Achievements

脊椎動物の個体レベルの老化制御機構の理解は未だ黎明期であり、代謝という切り口から新規個体老化制御機構を解き明かした点に意義がある。これら機構は系統間比較から見出したものであり、寿命の個体差の理解などにもつながる可能性がある。また、代謝経路や代謝物は生物種間で非常に保存性が高いため、本研究が見出した代謝物や代謝酵素の抗老化に関する機能は、脊椎動物で普遍的な老化制御メカニズムである可能性が高く、ヒトの健康寿命延伸技術の開発につながることも期待される。