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

Understanding the role that genetic variation plays in setting life span remains one of the challenges of biology. There is a clear connection between nutrient inputs, energy sensing pathways, and life span variation. However, despite the role of central metabolic enzymes in energy homeostasis and their metabolites as nutrient level signals, little is known about how gene expression variation impacts life span. In this report, we use P-element mutagenesis in Drosophila to study the effect on life span of moderate reductions in expression of seven important central metabolic enzymes (Hex-A, Hex-C, Gdh, Gpdh, Men, Idh, and Mdh2). We examine and contrast these genotypic effects on both normal diets and dietary restriction. The observation of major significance is that in five of seven genes (Hex-A, Hex-C, Mdh2, Gdh, Gpdh) the reduction of gene expression significantly extends life span on one or both diets. Redox balance is a factor in aging, and two genes (Gpdh, Gdh) are involved in NAD/NADH redox balance, and we observe that lower activity genotypes significantly extend life span. Furthermore, both hexokinases show extension of life span with reduced gene activity. Since both potentially affect the ATP/ADP ratio, this outcome connects with the emerging role of AMP-activated protein kinase (AMPK) as an energy sensor in regulating life span and mediating caloric restriction in Drosophila. Our results show that genetic variation in metabolic genes is a potential determinant of life span variation. These genes possess significant expression variation in natural populations, and our experimental genotypes span this level of natural activity variation. Some genes are involved with a major axis of gene expression variation seen across latitudinal populations in North America in earlier studies. Our studies clearly link the readout of energy-state with the perturbation of the genes of central metabolism and this has significant effects on life span.