Unraveling novel pathological mechanism of frailty targeting vascular inflammation
| Project/Area Number |
18H02726
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小川 純人 東京大学, 医学部附属病院, 准教授 (20323579)
孫 輔卿 東京大学, 医学部附属病院, 届出研究員 (20625256)
小島 太郎 東京大学, 医学部附属病院, 講師 (40401111)
亀山 祐美 東京大学, 医学部附属病院, 助教 (60505882)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Keywords | 血管炎症 / フレイル / 階層構造 / 老化 / 大動脈瘤 / サルコペニア / 慢性炎症 / 認知症 |
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| Outline of Final Research Achievements |
Hierarchical relationship between aging and dysfunction of frailty-related tissues might exist via chronic inflammation. In this study, we aimed unravelling the mechanism of this hierarchical relationship focusing on vascular inflammation, as an upstream trigger of chronic inflammation. Furthermore, apoptosis of vascular cells is one of important phenomenon increasing inflammation.
Our results show that in vitro apoptosis of vascular cell was associated with IL-1 upregulation and in vivo inflammation-derived aneurysm formation was enhanced by aging factors such high phosphate or deficiency of sex hormone through apoptosis and inflammation. Furthermore, aneurysm caused increase in activated microglia in hippocampus and decrease in muscle mass and bone mineral density in skeletal muscle, which suggests hierarchical structure started from vascular disease to frailty-related tissues including hippocampus and skeletal muscle.
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| Academic Significance and Societal Importance of the Research Achievements |
老化基盤である慢性炎症からフレイル病態機序を明らかにすることは、フレイル予防・診断及び治療の戦略策に一助となる。
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Report
(4 results)
Research Products
(61 results)
