Dietary restriction in Drosophila

Abstract

The fruit fly Drosophila is a useful organism for the investigation of the mechanisms by which dietary restriction (DR) extends lifespan. Its relatively short generation time, well-characterised molecular biology, genetics and physiology and ease of handling for demographic analysis are all major strengths. Lifespan has been extended by DR applied to adult Drosophila, by restriction of the availability of live yeast or by co-ordinate dilution of the whole food medium. Lifespan increases to a maximum through DR with a progressive dilution of the food and then decreases through starvation as the food is diluted further. Daily and lifetime fecundities of females are reduced by food dilution throughout the DR and starvation range. Standard Drosophila food ingredients differ greatly between laboratories and fly stocks can differ in their responses to food dilution, and a full range of food concentrations should therefore be investigated when examining the response to DR. Flies do not alter the time that they spend feeding in response to DR. Both mean and maximum lifespan are extended by DR. The nutrients critical for the response to DR in Drosophila require definition. The extension of lifespan in response to DR is very much greater in females than in males. Two nutrient-sensing pathways, the insulin/IGF-like and TOR pathways, have been implicated in mediating this response of lifespan to DR in Drosophila, as have two protein deacetylases, dSir2 and Rpd3, although the precise nature of this interaction remain to be characterised. Although female fecundity is reduced by DR, the response of lifespan to DR appears normal in sterile females, possibly implying that reduced fecundity is not necessary for extension of lifespan by DR. There is no reduction in metabolic rate or in the rate of generation of superoxide and hydrogen peroxide from isolated mitochondria in response to DR. DR acts acutely and rapidly (within 48 h) to reduce the mortality of flies that are fully fed to the level found in animals exposed to DR throughout life. This rapid mortality rate recovery provides a powerful framework within which to further investigate the mechanisms by which DR extends lifespan.