An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster
An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster
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DOI：
10.1073/pnas.0403493101
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发表时间：
2004-08-31
影响因子：
11.1
通讯作者：
Helfand, SL
中科院分区：
文献类型：
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作者：
Bauer, JH;Goupil, S;Helfand, SL
衰老研究的最新进展揭示了影响酵母、线虫、苍蝇和老鼠等多种生物寿命的基因和遗传途径。影响寿命的基因和药物的发现被推迟了，因为除了生存能力之外，没有其他表型，生存能力取决于人口中个体死亡时的年龄测量。使用生存率来确定延长生命的遗传和药理干预是耗时的，需要大量的同质动物。在这里，我们报告了一种在果蝇中使用分子生物标志物表达的检测方法的发展，该方法可以加速评估潜在的改变寿命的干预措施的能力。将年龄依赖性分子生物标志物的表达与致命毒素结合起来，可以将进行寿命研究所需的时间减少80%。该试验概括了三个最知名的环境寿命延长干预措施的影响，在苍蝇：环境温度，生殖状态，和热量减少。已知延长果蝇寿命的单基因突变，如Indy和rpd3，在该测定中也延长了寿命。我们使用这种测定作为筛选来鉴定延长苍蝇寿命的药物。硫辛酸和白藜芦醇在我们的测定中被鉴定为有益的，并且在正常实验室条件下显示出延长寿命。我们建议，这种测定可用于筛选药理学以及遗传干预更迅速地对寿命的积极影响。
Recent advances in aging research have uncovered genes and genetic pathways that influence lifespan in such diverse organisms as yeast, nematodes, flies, and mice. The discovery of genes and drugs that affect lifespan has been delayed by the absence of a phenotype other than survivorship, which depends on the measurement of age at death of individuals in a population. The use of survivorship to identify genetic and pharmacological interventions that prolong life is time-consuming and requires a large number of homogeneous animals. Here, we report the development of an assay in Drosophila melanogaster using the expression of molecular biomarkers that accelerates the ability to evaluate potential lifespan-altering interventions. Coupling the expression of an age-dependent molecular biomarker to a lethal toxin reduces the time needed to perform lifespan studies by 80%. The assay recapitulates the effect of the three best known environmental life-span-extending interventions in the fly: ambient temperature, reproductive status, and calorie reduction. Single gene mutations known to extend lifespan in the fly such as Indy and rpd3 also extend lifespan in this assay. We used this assay as a screen to identify drugs that extend lifespan in flies. Lipoic acid and resveratrol were identified as being beneficial in our assay and shown to extend lifespan under normal laboratory conditions. We propose that this assay can be used to screen pharmacological as well as genetic interventions more rapidly for positive effects on lifespan.