グルタミノリシスによるセノリシス阻害は,様々な年齢に関連する疾患を改善する

Yoshikazu Johmura¹, Takehiro Yamanaka², Satotaka Omori²

¹Division of Cancer Cell Biology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. mkt-naka@ims.u-tokyo.ac.jp johmuray@ims.u-tokyo.ac.jp.

Science (New York, N.Y.)

|January 15, 2021

まとめ

衰老する細胞は生存のためにグルタミンゼ1 (GLS1) に依存する. GLS1依存のグルタミン溶解を阻害することで,老化細胞を排除し,老化に関連した臓器機能障害を改善し,新しい溶解戦略を提供します.

科学分野:

細胞の老化
メタボリズム
老化に関する研究

背景:

衰老する細胞の除去であるセノリシスは老化に関連した病気の治療に有望な効果を示しています
衰老する細胞の生存を促す分子機構はほとんど不明です
老化細胞を標的とするには独特の代謝依存性を理解する必要があります

研究の目的:

人間の老化細胞の生存に不可欠な分子経路を特定する
高齢化細胞の生命力におけるグルタミン溶解の役割を調査する.
グルタミノリシスを阻害する治療の可能性を in vivoで評価する.

主な方法:

グルタミンゼ1 (GLS1) が老化細胞生存の鍵となる遺伝子を特定した.
リンソーム膜損傷,細胞内pH,腎臓型グルタミンゼ (KGA) 発現との関連を調査した.
高齢マウスの老化細胞と臓器機能に対するKGA抑制の影響を評価した.

主要な成果:

衰老細胞の細胞内pHが低下すると,KGAの発現が上昇する.
強化されたグルタミン溶解はアンモニアを産生し,低pHを中和し,老化の細胞の生存を促進します.
高齢マウスのKGA依存性グルタミノリシスの抑制
ターゲッテッド・セノリシスにより,年齢に関連する臓器機能障害が改善されました.

結論:

衰老する細胞はグルタミノリシスに依存しています
GLS1とKGA依存のグルタミノリシスは老化細胞の生存維持に不可欠である.
グルタミン溶解を阻害することは,老化と年齢関連の病変と戦うための有望な治療戦略です.

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