Identification of novel senolytic drugs to treat age-related diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07316
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Juntendo University (2021); Niigata University (2019-2020)
• Principal Investigator: Katsuumi Goro 順天堂大学, 医学部, 特任助教 (60815356)
• Co-Investigator(Kenkyū-buntansha): 清水 逸平 順天堂大学, 医学部, 准教授 (60444056) ; 南野 徹 順天堂大学, 医学部, 教授 (90328063)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 細胞老化 / 老化細胞除去

Outline of Final Research Achievements

This study was aimed to identify a novel senolytic reagent effective for cardiometabolic disease in compounds already available in clinical settings. We found a compound called "Seno-7284" exhibits senolytic effect in murine models of type 2 diabetes, atherosclerosis and progeroid. Seno-7284 reduced the accumulation of senescent cells in visceral adipose tissue of Diabetic mice. This associated with the suppression in systemic glucose intolerance, and adipose tissue inflammation. Administrating Seno-7284 also reduced accumulation of senescent cells in atherosclerotic lesion in aorta of ApoE-KO mice, and inhibited the progression of atherosclerosis. This drug significantly improved the lifespan of Zmpste24 KO progeroid mice. Further analysis indicated that Seno-7284 increase AICAR level in blood and stimulates endogenous senolytic function of NK cells and CD8+ T cells via Cxcl9-Cxcr3 axis. Collectively, Seno-7284 would become promising therapies for age-related disorders

Free Research Field

細胞老化

Academic Significance and Societal Importance of the Research Achievements

老化細胞除去治療は加齢関連性疾患の治療のみならず「老化」自体を治療可能な次世代の治療法として注目を集めており、その臨床応用のインパクトは大きい。Seno-7284は既に臨床応用に至っている薬剤であり、その応用は新規に薬剤を導出するよりもはるかに容易である。
また、老化細胞除去に内因性の免疫機能の関与を示したことは新たな知見であり、本領域における研究に一定の学術的意義をもたらしたと考えている。