Department of Pathology and Programs in Neuroscience and Cancer Biology, Stanford University School of Medicine, Stanford, CA 94303, United States of America.
Department of Pathology and Programs in Neuroscience and Cancer Biology, Stanford University School of Medicine, Stanford, CA 94303, United States of America; Crystal Springs Uplands School, Hillsborough, CA 94010, United States of America.
Exp Gerontol. 2018 Nov;113:10-17. doi: 10.1016/j.exger.2018.09.014. Epub 2018 Sep 21.
Recent studies suggest that moderate red wine consumption may confer several health benefits, including protection against heart disease, certain cancers and multiple age-related neurological diseases such as Alzheimer's disease. These health benefits are assumed to come from a compound from grape skin called resveratrol, which has been proposed to be a pro-longevity agent. Whether resveratrol accounts for all the health benefits of grape-derived nutrients and the molecular and cellular mechanisms underlying the beneficial effects of such nutrients are not well understood. Here we investigated the effect of supplementing grape skin extract (GSE) left from red wine-production process to the daily food intake of a Drosophila melanogaster model of Parkinson's disease (PD) associated with PTEN-induced kinase 1 (PINK1) loss-of-function. Consumption of GSE resulted in rescue of mitochondrial morphological defects, improvement of indirect flight muscle function and health-span, and prolonged lifespan of the PINK1 mutant flies. Further biochemical and genetic studies revealed a link between activation of mitophagy and the beneficial effects of GSE. Our results indicate that GSE can promote autophagy activation, preserve mitochondria function, and protect against PD pathogenesis, and that the beneficial effect of GSE in mitophagy activation is not accounted for by resveratrol alone.
最近的研究表明，适量饮用红酒可能对人体健康有多种益处，包括预防心脏病、某些癌症和多种与年龄相关的神经退行性疾病，如阿尔茨海默病。这些健康益处被认为来自葡萄皮中的一种化合物白藜芦醇，它被认为是一种长寿剂。然而，白藜芦醇是否能完全解释源自葡萄的营养物质的所有健康益处，以及这种营养物质的有益作用的分子和细胞机制尚不清楚。在这里，我们研究了在与 PTEN 诱导的激酶 1（PINK1）功能丧失相关的帕金森病（PD）的黑腹果蝇模型的日常饮食中补充红酒生产过程中剩余的葡萄皮提取物（GSE）对其的影响。GSE 的摄入导致线粒体形态缺陷得到挽救，间接飞行肌功能和健康寿命得到改善，以及 PINK1 突变果蝇的寿命延长。进一步的生化和遗传研究揭示了自噬激活与 GSE 有益作用之间的联系。我们的研究结果表明，GSE 可以促进自噬的激活，维持线粒体功能，并预防 PD 的发病机制，而且 GSE 在自噬激活中的有益作用不能仅仅归因于白藜芦醇。
