Analysis for a role of vascular senescence in age-related disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kyoto Prefectural University of Medicine (2020-2021); Kobe Pharmaceutical University (2019)
• Principal Investigator: Ikeda Koji 京都府立医科大学, 医学(系)研究科(研究院), 教授 (90423871)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 血管内皮細胞 / 老化 / 代謝疾患 / 動脈硬化 / 細胞老化

Outline of Final Research Achievements

We have analyzed a role of senescent endothelial cells (EC) in age-related metabolic and atherosclerotic diseases by using EC-specific progeroid mice. We identified that senescent ECs cause premature senescence and dysfunction of adipocytes, leading to systemic metabolic disorders. By using parabiosis model, we revealed that senescent ECs induce adipocyte dysfunction through soluble secreted factors.
Also, we mated these EC-specific progeroid mice with ApoE-KO mice, and analyzed a role of EC senescence in atherosclerosis. We identified that NF-kB signaling is enhanced in senescent ECs because of epigenetic modification, which enhance adhesion molecules expression in ECs and exacerbate atherosclerosis in EC-specific progeroid mice. These data clearly revealed a direct and causative role of senescent ECs in age-related metabolic and atherosclerotic diseases, and thus senescent ECs are potential therapeutic target for prevention of age-related diseases.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

世界中の先進国では人口の高齢化が進んでおり、特に本邦は世界的にも群を抜いた超高齢化社会となっている。今後、超高齢化社会を健全に継続・維持していくためには健康寿命を延伸し、高齢者の社会活動を増やしながら医療費を削減していくことが必須である。そのためには老化および老化関連疾患の未知の分子機構を解明し、新たな治療・予防標的を見出す必要がある。本研究成果から血管内皮細胞の老化が代謝異常や動脈硬化を進展・増悪させる重要な因子であることが明らかとなった。老化血管内皮細胞は老化関連疾患を予防・治療するための新しい標的として大変有望である。