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- W2980492799 abstract "Accumulation of senescent cells is promoted in various organs as aging, and it also contributes to the progression of age-related disorders. Recent reports have demonstrated the elimination of senescent cells, so-called senolysis ameliorated various age-related disorders including cardiovascular diseases. However, there is currently no senolytic drug available in clinical settings. Here, we found a novel senolytic drug (termed “seno-7284”) from those already used in clinical setting and it exhibited senolytic effect in murine models of type 2 diabetes, atherosclerosis and progeroid aging. Conducting senescence-associated beta-galactosidase staining(SA-beta gal), we found that administrating seno-7284 for one week significantly reduced the accumulation of senescent cells in viscerala dipose tissue of diabetic mice induced by fed high-fat diet(Figure). This drug also ameliorated systemic glucose metabolism and adipose tissue inflammation without a reduction of body weight. Further analysis including RNA-seq analysis suggested seno-7284 stimulates the endogenous senolytic function of NK cells and CD8+ T cells via the Cxcl9-Cxcr3 axis. We also found administrating seno-7284 for two weeks also reduced the accumulation of senescent cells and atherosclerotic lesions in the aorta of western-diet-fed ApoE knock out mice. Surprisingly, this drug significantly improved the lifespan of Zmpste24 KO progeroid aging mice. Correctively, our results indicate that seno-7284 mediates its senolytic effect through the recruitment of lymphocytes. Senolytics would become a promising therapy for aging and age-related cardiometabolic disorders." @default.
- W2980492799 created "2019-10-25" @default.
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- W2980492799 date "2019-08-02" @default.
- W2980492799 modified "2023-09-25" @default.
- W2980492799 title "Abstract 752: A Novel Senolytic Drug, Seno-7284 Ameliorates Aging and Age-related Cardiometabolic Disorders" @default.
- W2980492799 doi "https://doi.org/10.1161/res.125.suppl_1.752" @default.
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