Nutrient control of Drosophila longevity

• Drosophila is a physiologic genetic model that can be used determine how dietary restriction extends lifespan.
• Reduced insulin/IGF extends fly lifespan, but may not mediate dietary restriction aging.
• New tools to study dietary restriction are discussed, including the Nutritional Geometric Framework and holidic diet.
• Dietary restriction may extend lifespan by limiting amino acids alone or relative to carbohydrates.

Dietary restriction (DR) extends the lifespan of many animals, including Drosophila melanogaster. Recent work with flies shows that longevity is controlled by the ratio of consumed protein relative to carbohydrates. Given that reduced insulin and/or insulin-like growth factor (IGF) and target of rapamycin (TOR) signaling increase Drosophila lifespan, these pathways are candidate mediators of DR. However, this idea has ambiguous experimental support. The Nutritional Geometric Framework (NGF), which dissects the impact of nutrient protein relative to carbohydrates, may provide an approach to resolving the roles for these pathways in DR. Nutrient sensing of protein and carbohydrate may occur in the fat body through signals to hypothalamic-like neurons in the fly brain and, thus, control secretion of insulin-like peptides that regulate longevity.