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.营养输入、能量感知通路、寿命变异与衰老之间存在紧密关联。尽管代谢酶在能量稳态中发挥关键作用，且其代谢产物可作为营养信号分子，但目前学界对这类酶的基因表达如何影响寿命仍所知有限。本研究通过在果蝇（Drosophila）中开展P因子诱变（P-element mutagenesis）实验，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两种条件下的效果差异。核心研究结果显示：7个目标基因中有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，我们观察到活性较低的对应基因型可显著延长寿命。己糖激酶（hexokinases）在基因活性下调后，同样表现出寿命延长的效应。由于这两类基因均会影响ATP/ADP比值，这一发现与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。此外，这些基因在自然种群中存在显著的表达变异，且本研究的实验基因型覆盖了该自然活性变异的水平。本研究将能量状态的感知与核心代谢基因的扰动建立了关联，并证实了这类基因对寿命的调控作用。