The plate half-full: status of research on the mechanisms of dietary restriction in Drosophila melanogaster.

It has been almost two decades since dietary restriction was first shown to increase Drosophila lifespan. Since then, understanding this phenomenon advanced as groups worked to identify what quality of restricted diet matters: calories or a specific nutrient. The problem is complex because is it difficult to measure what a fly actually consumes. A powerful solution uses the geometric framework of nutrition where diets in many combinations can be tested for their effects on lifespan and reproduction while measuring intake. Applied to Drosophila, it is now clear that specific nutrients, not calories, mediate longevity. The geometric framework also reveals a nutritional basis for the trade-off between reproduction and lifespan. This complements a stable-isotope analysis that tracked the allocation of nitrogen, carbon and essential amino acids into eggs versus reproduction. Together, these studies show that it is not possible to explain how DR extends lifespan through a mechanism were resources are simply reallocated to somatic maintenance away from reproduction. Although promising in principle, genetic analysis of DR mechanisms has had limited success. To be productive, studies must include enough diets at appropriate concentrations. In reviewing the best data, there is little evidence to date for any gene to be required for DR to increase Drosophila lifespan, including insulin signaling or 4eBP. Strong analyses of genes required for DR should be a priority in future research with Drosophila and this may be made most robust by considering the effect of mutants in the context of the geometric framework.