Resveratrol improves health and survival of mice on a high-calorie diet
Resveratrol improves health and survival of mice on a high-calorie diet
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DOI：
10.1038/nature05354
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发表时间：
2006-11-16
期刊：
影响因子：
64.8
通讯作者：
Sinclair, David A.
中科院分区：
文献类型：
--
作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
白藜芦醇(3，5，4‘-三羟基二苯乙烯)可延长各种物种的寿命，包括酿酒酵母、秀丽线虫和黑腹果蝇。在这些生物中，寿命的延长依赖于Sir2，一种保守的脱乙酰酶，被认为是卡路里限制的有益效果的基础。在这里，我们展示了白藜芦醇将高卡路里饮食的中年小鼠的生理学转变为标准饮食的小鼠的生理，并显着提高了它们的存活率。白藜芦醇会产生与寿命延长相关的变化，包括增加胰岛素敏感性、降低胰岛素样生长因子-1(IGF-I)水平、增加AMP激活的蛋白激酶(AMPK)和过氧化体增殖物激活的受体-伽玛共激活物1α(PGC-1α)的活性、增加线粒体数量和改善运动功能。基因集丰富的参数分析显示，在153条显著改变的通路中，有144条白藜芦醇与高卡路里饮食的效果相反。这些数据表明，使用小分子改善哺乳动物的总体健康是一个可以实现的目标，并指出了治疗肥胖相关疾病和老年病的新方法。
Resveratrol ( 3,5,4'- trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle- aged mice on a high- calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin- like growth factor- 1 ( IGF- I) levels, increased AMP- activated protein kinase ( AMPK) and peroxisome proliferator- activated receptor-gamma coactivator 1 alpha ( PGC- 1 alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high- calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity- related disorders and diseases of ageing.