Identification of gingerenone A as a novel senolytic compound
Senescent cells accumulate with aging and have been shown to contribute to age-associated diseases and organ dysfunction. Eliminating senescent cells with senolytic drugs has been shown to improve age phenotypes in mouse models and there is some initial evidence that it may improve the health of persons with chronic diseases. In this study, we employed WI-38 human fibroblasts rendered senescent by exposure to ionizing radiation (IR) to screen several plant extracts for their potential senolytic and/or senomorphic activity. Of these, ginger extract (Zingiber officinale Rosc.) selectively caused the death of senescent cells without affecting proliferating cells. Among the major individual components of ginger extract, gingerenone A and 6-shogaol showed promising senolytic properties, with gingerenone A selectively eliminating senescent cells. Similar to the senolytic cocktail dasatinib and quercetin (D+Q), gingerenone A and 6-shogaol elicited an apoptotic program. Additionally, both D+Q and gingerenone A had a pronounced effect on suppressing the senescence-associated secretory phenotype (SASP). Gingerenone A selectively promotes the death of senescent cells with no effect on non-senescent cells and these characteristics strongly support the idea that this natural compound may have therapeutic benefit in diseases characterized by senescent cell accumulation.
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基因水平:PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平:MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平:细胞染色、细胞分选、细胞培养、细胞功能
组织水平:空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析:流式数据分析、组化数据分析、多因子数据分析
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