Data from: Genetic perturbation of key central metabolic genes extends life span in Drosophila and affects response to dietary restriction

There is a connection between nutrient inputs, energy-sensing pathways, lifespan variation and aging. Despite the role of metabolic enzymes in energy homeostasis and their metabolites as nutrient signals, little is known about how their gene expression impacts lifespan. In this report, we use P-element mutagenesis in Drosophila to study the effect on lifespan of reductions in expression of seven central metabolic enzymes, and contrast the effects on normal diet and dietary restriction. The major observation is that for five of seven genes, the reduction of gene expression extends lifespan on one or both diets. Two genes are involved in redox balance, and we observe that lower activity genotypes significantly extend lifespan. The hexokinases also show extension of lifespan with reduced gene activity. Since both affect the ATP/ADP ratio, this connects with the role of AMP-activated protein kinase as an energy sensor in regulating lifespan and mediating caloric restriction. These genes possess significant expression variation in natural populations, and our experimental genotypes span this level of natural activity variation. Our studies link the readout of energy state with the perturbation of the genes of central metabolism and demonstrate their effect on lifespan.营养摄入、能量感知通路、寿命变化与衰老之间存在密切关联。尽管代谢酶参与能量稳态调控，且其代谢产物可作为营养信号分子，但目前学界对这些酶的基因表达如何影响寿命仍知之甚少。本研究以果蝇（Drosophila）为模型，通过P因子诱变（P-element mutagenesis）技术，探究7种核心代谢酶的表达下调对寿命的影响，并对比了正常饮食与饮食限制（dietary restriction）条件下的实验结果差异。核心实验结果显示，7个基因中有5个的表达下调可在一种或两种饮食条件下延长受试个体的寿命。其中2个基因参与氧化还原平衡调控，实验发现其活性降低的基因型可显著延长寿命。己糖激酶（hexokinases）同样表现出基因活性下调时寿命延长的现象。由于这两类基因均会影响ATP/ADP比值，该发现与AMP活化蛋白激酶（AMP-activated protein kinase）作为能量感受器在调控寿命及介导热量限制中的作用机制相契合。上述基因在自然种群中存在显著的表达差异，且本研究使用的实验基因型覆盖了该自然活性变异的范围。本研究将能量状态的感知与核心代谢基因的扰动效应建立了关联，并证实了这些基因对寿命的调控作用。