Bass Timothy M, Weinkove David, Houthoofd Koen, Gems David, Partridge Linda
Department of Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Mech Ageing Dev. 2007 Oct;128(10):546-52. doi: 10.1016/j.mad.2007.07.007. Epub 2007 Aug 14.
It was recently reported that the plant polyphenol resveratrol, found, e.g., in grape berry skins, extended lifespan in the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans. This lifespan extension was dependent on an NAD(+)-dependent histone deacetylase, Sir2 in Drosophila and SIR-2.1 in C. elegans. The extension of lifespan appeared to occur through a mechanism related to dietary restriction (DR), the reduction of available nutrients without causing malnutrition, an intervention that extends lifespan in diverse organisms from yeast to mammals. In Drosophila, lifespan extension by DR is associated with a reduction in fecundity. However, a slight increase in fecundity was reported upon treatment with resveratrol, suggesting a mode of action at least partially distinct from that of DR. To probe this mechanism further, we initiated a new study of the effects of resveratrol on Drosophila. We saw no significant effects on lifespan in seven independent trials. We analysed our resveratrol and found that its structure was normal, with no oxidative modifications. We therefore re-tested the effects of resveratrol in C. elegans, in both wild-type and sir-2.1 mutant worms. The results were variable, with resveratrol treatment resulting in slight increases in lifespan in some trials but not others, in both wild type and sir-2.1 mutant animals. We postulate that the effect of resveratrol upon lifespan in C. elegans could reflect induction of phase 2 drug detoxification or activation of AMP kinase.
最近有报道称，植物多酚白藜芦醇（例如在葡萄皮中发现）可延长果蝇和秀丽隐杆线虫的寿命。这种寿命延长依赖于一种依赖NAD⁺的组蛋白脱乙酰酶，果蝇中的Sir2和秀丽隐杆线虫中的SIR-2.1。寿命延长似乎是通过一种与饮食限制（DR）相关的机制发生的，即减少可利用的营养物质而不导致营养不良，这种干预措施能延长从酵母到哺乳动物等多种生物的寿命。在果蝇中，饮食限制导致的寿命延长与繁殖力降低有关。然而，有报道称用白藜芦醇处理后繁殖力略有增加，这表明其作用模式至少部分不同于饮食限制。为了进一步探究这种机制，我们启动了一项关于白藜芦醇对果蝇影响的新研究。在七项独立试验中，我们未发现对寿命有显著影响。我们分析了我们的白藜芦醇，发现其结构正常，没有氧化修饰。因此，我们在野生型和sir-2.1突变型线虫中重新测试了白藜芦醇的效果。结果各不相同，在一些试验中，白藜芦醇处理使野生型和sir-2.1突变型动物的寿命略有增加，而在其他试验中则没有。我们推测白藜芦醇对线虫寿命的影响可能反映了2期药物解毒的诱导或AMP激酶的激活。
