Elucidation of the mechanism of age-related functional decline of BBB in terms of cellular senescence

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16612
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Osaka University
• Principal Investigator: Matsudaira Tatsuyuki 大阪大学, 微生物病研究所, 特別研究員(CPD) (20812267)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 細胞老化 / 血管内皮細胞

Outline of Final Research Achievements

Age-related blood-brain barrier (BBB) dysfunction can contribute to neurodegenerative diseases as well as cerebrovascular diseases, but the detailed mechanism of BBB dysfunction has not been fully elucidated. In this study, we focused on the cellular senescence of vascular endothelial cells as a cause of BBB functional decline. We compared the gene expression of cerebrovascular endothelial cells of young and old mice, but no significant difference was observed between them from the viewpoint of cellular senescence. However, we found that inflammatory properties are enhanced in cerebral vascular endothelial cells of aged mice and identified vascular endothelial cell-specific gene candidates that can suppress inflammation. We will investigate in more detail whether they can suppress inflammation of vascular endothelial cells at the mouse level.

Free Research Field

細胞老化

Academic Significance and Societal Importance of the Research Achievements

血液脳関門（BBB）は神経細胞への栄養素の選別、毒素の遮断、変性タンパク質蓄積の防止などを担うが、これらの機能が加齢に伴い低下することが報告されている。BBBの機能低下の要因の一つがBBB構成細胞の細胞老化であることが明らかになれば、他の組織で理解が進んでいる細胞老化の研究をこの研究領域に生かせるだけでなく、老化細胞選択的な除去薬の適応も選択肢となり、加齢に伴う脳機能低下や神経変性疾患防止の新たなアプローチを見出すことが期待される。