Elucidation of the regulatory mechanisms of cellular senescence using a novel mouse model to establish the molecular basis of aging

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03431
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Kanazawa University (2022); The University of Tokyo (2019-2021)
• Principal Investigator: Johmura Yoshikazu 金沢大学, がん進展制御研究所, 教授 (40616322)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 細胞老化 / 細胞周期 / 一細胞解析 / 慢性炎症 / 非アルコール性脂肪肝炎 / 個体老化

Outline of Final Research Achievements

Recently, molecular genetic analysis has shown that artificially removing senescent cells from old individuals significantly delays the onset of age-related diseases and even extends life span itself, indicating that the accumulation of senescent cells is one of the main causes of individual aging. However, the mechanisms of induction, removal, and accumulation of senescent cells in vivo and the molecular basis for senescent cell-induced individual aging remain unclear. In this study, we establishedand analhyzed mice in which senescent cells can be identified, isolated, and traced at the single-cell level, and genetically engineered mice specific for senescent cells, to clarify the mechanisms of induction, removal, and accumulation of senescent cells in vivo and their roles.

Free Research Field

老化生物学

Academic Significance and Societal Importance of the Research Achievements

老化細胞を一細胞レベルで同定・検出できるマウスを用いた老化細胞の動態・性状解析により、生体内における老化細胞は多様性に富んでいることを見出すとともに、がん治療でも使用されている免疫チェックポイント阻害剤の老化病態治療への応用につながる知見を得ることができた。また、老化細胞の蓄積やそれを起点とした慢性炎症が個体老化や加齢関連疾患の病態の基盤であることも明らかにすることができた。本研究成果は、21世紀の先進医療において重要課題の一つである老化・老年病の予防法の開発につながるとことが期待される。