Mechanisms of mitochondrial disease suppression and lifespan extension by lactic acid bacteria

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K11553
• 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: Institute of Physical and Chemical Research
• Principal Investigator: Ito Takashi 国立研究開発法人理化学研究所, 環境資源科学研究センター, 上級研究員 (20597124)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ミトコンドリア / 寿命 / 乳酸菌 / 乳酸 / 解糖系

Outline of Final Research Achievements

In mice with mitochondrial abnormalities (Ndufs4 KO), oral administration of lactic acid as well as lactic acid bacterial strains extended healthy lifespan. Furthermore, microglial activation and neuronal cell death were reduced by both administrations. We also found that lactate inhibits the glycolysis and enhances mitochondrial respiration, a phenomenon commonly seen in many cell lines. Lactate commonly enhanced respiration in cell types differentiated from iPS cell lines posessing mitochondrial disease-causing mutations, including Ndufs4 KO. Our results show that oral administration of lactic acid or intervention onto the gut microbiota can improve mitochondrial function and suppress neuroinflammation, warranting further investigations. In this study, we present a novel possibility that oral administration of microorganisms and their metabolites may be an effective way to complement mitochondrial abnormalities.

Free Research Field

長寿の生物学

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアは、我々が活動するためのエネルギーの産生など、生命活動の根幹を担う。ミトコンドリア異常が多くの疾患や個体の老化に関わる一方で、一度機能が低下したミトコンドリアの機能を回復することは基礎研究のレベルでもとても難しく、ミトコンドリア異常をよくする効果的な治療法開発・社会実装には至っていない。我々は乳酸や乳酸菌により、ミトコンドリア異常を改善できること、モデル生物の寿命を延長できることを見つけた。さらにそのメカニズムの一端を明らかにした。今回の結果は、小児ミトコンドリア病や老化などの現状で治療がとても難しい症状を理解し、将来的な治療法の開発に役立つことが期待される。