The Role of Estrogen in Frailty Suppression Mechanisms: Focusing on Inflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15660
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nanao -Hamai Michiko 東京大学, 医学部附属病院, 助教 (40876091)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: エストロゲン / フレイル / 炎症 / 血管老化

Outline of Final Research Achievements

In female mice (C57BL/6JJmsSlc, 20 weeks old), the formation of aortic aneurysms was enhanced by ovariectomy combined with vascular inflammation, and this was suppressed by E2 supplementation. It was suggested that E2 suppresses vascular inflammation and aortic aneurysm formation through the inhibition of inflammatory cytokines such as IL-6 and IL-1β. Studies using peritoneal macrophages and mouse macrophage-like RAW264.7 cells showed that E2 acts suppressively in response to LPS stimulation.

In muscles, ovariectomy combined with vascular inflammation resulted in a decrease in the weight of the soleus muscle (with no change in gastrocnemius muscle weight) and a reduction in grip strength (with no change in endurance). Both were recovered by E2 supplementation, suggesting that E2 acts to suppress inflammation in certain muscles and muscle functions.

Free Research Field

老年医学

Academic Significance and Societal Importance of the Research Achievements

女性では、更年期以降エストロゲンの分泌が低下し、加齢と共に動脈硬化や骨粗鬆症、サルコペニア、認知症の発症リスクが高まることが知られている。本研究によってE2減少が引き起こす炎症制御の破綻による慢性炎症が、フレイル関連臓器、特に血管と筋肉の機能低下・老化を引き起こすことが示唆された。今後、フレイル予防薬としての新たな選択的エストロゲン受容体調節薬の開発が期待される。