Moaddel Ruin, Sanehira Chad, Keyes Gregory, Cui Chang-Yi, Ahmadkhania Reza, Candia Julián, Price Nathan L, Eckroth Sarah, Middleton Bryce, Khadeer Mohammed, Mazucanti Caio H, McDevitt Ross A, Gorospe Myriam, de Cabo Rafael, Egan Josephine M, Ramsden Christopher E, Ferrucci Luigi
Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, USA.
Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, USA.
NPJ Aging. 2025 May 30;11(1):45. doi: 10.1038/s41514-025-00230-3.
Senescent cells accumulate with aging and are associated with several age-associated diseases and functional declines. Eliminating senescent cells with senolytics improves aging phenotypes in mouse models and may improve the health of people with chronic diseases. To date, very few senotherapeutic (senolytics and senomorphics) compounds have been identified. In a recent study, we reported that gingerenone A (GinA) has a senolytic effect via mechanisms including the activation of caspase-3 activity and apoptotic cell death. In this study, we investigated whether GinA has senotherapeutic properties in a mouse model of senescence. Moreover, we modified GinA with eicosapentaenoic acid (EPA) esters (GinA-EPA) or docosahexaenoic acid (DHA) esters (GinA-DHA) to generate modified gingerenone A (modGinA) that could enhance GinA effects. We found that both GinA and modGinA induced biochemical and histological changes consistent with anti-inflammatory, senolytic, and senomorphic effects, leading to improved metabolic and mitochondrial functions.
衰老细胞会随着年龄增长而积累，并与多种与年龄相关的疾病和功能衰退有关。使用衰老细胞裂解剂清除衰老细胞可改善小鼠模型中的衰老表型，并可能改善慢性病患者的健康状况。迄今为止，已鉴定出的衰老治疗（衰老细胞裂解剂和衰老细胞形态调节剂）化合物非常少。在最近的一项研究中，我们报告称姜烯酮A（GinA）通过包括激活半胱天冬酶-3活性和凋亡性细胞死亡在内的机制具有衰老细胞裂解作用。在本研究中，我们调查了GinA在衰老小鼠模型中是否具有衰老治疗特性。此外，我们用二十碳五烯酸（EPA）酯（GinA-EPA）或二十二碳六烯酸（DHA）酯（GinA-DHA）修饰GinA，以生成可增强GinA作用的修饰姜烯酮A（modGinA）。我们发现GinA和modGinA均诱导了与抗炎、衰老细胞裂解和衰老细胞形态调节作用一致的生化和组织学变化，从而改善了代谢和线粒体功能。
