Analysis of mechanisms controlling organismal aging of vertebrates focusing on an interaction between gut microbiota and post-lysosome signaling.

2023 Fiscal Year Final Research Report

• Project Area: Post-lysosome: Understanding of Higher-order Biological Processes initiated by the site of degradation
• Project/Area Number: 21H05148
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (III)
• 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): 2021-08-23 – 2024-03-31
• Keywords: 老化 / 寿命 / リソソーム / ターコイズキリフィッシュ

Outline of Final Research Achievements

By using an ultra-short-lived fish, turquoise killifish, I examined novel mechanisms regulating organismal aging of vertebrates focusing on a “post-lysosome signaling”. As a result, I got three findings as follows: (1) maintenance of gut health state by a ceramidase is suggested to regulate organismal-level aging through modulation of endocrine hormones produced in the brain, (2) an activation of lipid metabolism in lysosome extends the lifespan of a vertebrate model, (3) germ-cell removal, a possible manipulation activating “lysosome signaling”, regulates lifespan of vertebrates.

Free Research Field

老化

Academic Significance and Societal Importance of the Research Achievements

リソソームを単なる分解の終着点ではなく、シグナルの起点とするまったく新たな恒常性維持機構「ポストリソソームシグナル」の実態を、初めて脊椎動物において解析し、特に成果２では新規シグナル分子実体にも近づくことができた。成果１、３ではリソソームシグナルとの関連が期待される分子、生命現象を手掛かりとして、それぞれ腸や生殖細胞を起点とする新たな全身老化制御メカニズムを解き明かすことができた。これらの成果は「ポストリソソーム生物学」という革新的な研究領域の基盤となるものであり、また、健康寿命延伸のシーズを提供しうると期待される。