The developmental origins of adult health and disease are well established in human populations and mammalian models. For example, malnutrition during early life predisposes the future adult to an increased risk of metabolic disease. Despite much research in this area, the molecular mechanisms underlying this process of nutritional programing remain poorly understood. We have therefore established a Drosophila model for programing of adult metabolism and lifespan by the diet during development. We show that larval diet can program long-lasting perturbations of metabolism in adult flies. Importantly, larval diet can also dramatically increase median lifespan by up to 145%, a larger change than that obtained with adult dietary restriction (DR). Genetic manipulations suggest that the altered size of Insulin producing cells – analogous to β-cell mass in mammals – can explain only ~10% of this programed lifespan increase. We find, instead, that the programing mechanism depends upon endogenous compounds deposited onto the substrate, which alter the lifespan of both same- and opposite-sex adults. This reveals, for the first time, the existence of a transferrable component in the regulation of lifespan between same-sex animals. Biochemical, NMR, mass spectrometry and genetic approaches identify these compounds as a specific class of lipids that impact negatively upon lifespan in a dose-dependent manner. Importantly, the production of these toxic lipids by adults is programed by diet during development. We also find that the lifespan-extending effect of decreased Insulin signaling correlates with increased resistance to toxic lipids. Together, these findings establish Drosophila as a powerful new integrative physiology model for uncovering new mechanisms underlying the nutritional programing of metabolism and lifespan.