Genome wide association analysis with Drosophila to discover how metformin effects longevity

摘要 果蝇可以用来发现二甲双胍的潜在分子机制 效果寿命。在112个测试队列中，我们发现二甲双胍可以同样延长苍蝇的寿命 30%，但在其他条件下，该化合物同样减少了寿命。在此，我们建议 找出导致这种变异的遗传因素。我们将在全基因组范围内 与果蝇的关联性(GWA)分析，结合新兴的生物信息学分析 和分子验证研究。我们还提出了一种创新的桥梁方法 将果蝇的反应SNPs定位在同源基因上对人和小鼠的分析 哺乳动物的基因表达数据。我们将结合这些方法来解决如何 二甲双胍影响衰老，并通过哪些途径进行积极或消极的调节 寿命。

Summary Drosophila can be used to discover the underlying molecular mechanisms by which metformin effects lifespan. From 112 tested cohorts, we found metformin can extend fly lifespan as much as 30% but in other conditions the compound equally reduced lifespan. Here we propose to identify genetic factors that contribute to this variation. We will conduct a genome wide association (GWA) analysis with Drosophila, combined with emerging bioinformatic analytics and molecular validation studies. We propose as well, an innovative approach to bridge Drosophila analysis to humans and mice by mapping response SNPs of the fly onto orthologous gene expression data from mammals. We will combine these approaches to resolve how metformin affects aging, and through which pathways it positively or negatively modulates lifespan.