Developmental diet regulates Drosophila lifespan via lipid autotoxins

Abstract

Early-life nourishment exerts long-term influences upon adult physiology and disease risk. These lasting effects of diet are well established but the underlying mechanisms are only partially understood. Here we show that restricting dietary yeast during Drosophila development can, depending upon the subsequent adult environment, more than double median lifespan. Developmental diet acts via a long-term influence upon the adult production of toxic molecules, which we term autotoxins, that are shed into the environment and shorten the lifespan of both sexes. Autotoxins are synthesised by oenocytes and some of them correspond to alkene hydrocarbons that also act as pheromones. This study identifies a mechanism by which the developmental dietary history of an animal regulates its own longevity and that of its conspecific neighbours. It also has important implications for the design of lifespan experiments as autotoxins can influence the regulation of longevity by other factors including diet, sex, insulin signalling and population density.

Drosophila HNF4 Directs a Switch in Lipid Metabolism that Supports the Transition to Adulthood

“…Finally, adults normally emerge with low hydrocarbon levels that increase dramatically over 3 days, even in the absence of food, in agreement with the hypothesis that the larval adipose cells provide the primary source of precursors for hydrocarbon production (Figures 6A and S5A). These results are consistent with previous reports, which have shown that dietary manipulation during larval life affects the blend of hydrocarbons in young adults (Stefana et al, 2017;Wicker-Thomas et al, 2015). Altogether, these observations support the model that dHNF4 mediates the rapid conversion of persisting larval fat stores into hydrocarbons shortly after adult emergence.…”

“…Drosophila continuously shed and produce hydrocarbons throughout adulthood, indicating that this biosynthetic pathway is active at later stages to maintain a hydrophobic cuticle (Stefana et al, 2017). Consistent with this, we find that oenocytespecific dHNF4 RNAi in mature adults leads to a similar degree (D) Oil Red O stains are shown for oenocytes and adult fat bodies from 3-to 5-day-old starved controls (mCherry RNAi) and starved animals with adult-specific RNAi for dHNF4, KAR, ACC, FASN CG17374 , Cpr, or Cyp4g1 in oenocytes using PromE>, Tub-Gal80 ts .…”

Life-History Evolution and the Genetics of Fitness Components inDrosophila melanogaster

“…This phenomenon, first discovered in rats in 1935, has been examined by many studies in Drosophila, with a strong focus on understanding the molecular mechanisms underlying DR-induced longevity [for the first demonstration of DR in Drosophila see Chippindale et al (1993); also see Chapman and Partridge (1996), Mair et al (2003Mair et al ( , 2005 . While DR is usually implemented at the adult stage, several studies have found that a (not too strongly) restricted juvenile diet can also extend adult life span (Economos and Lints 1984;May et al 2015;Stefana et al 2017); remarkably, depending on the adult diet, larval yeast DR can double median life span, a carry-over effect caused by the larval diet-induced suppression of toxic, life span-shortening lipids produced by the adults (Stefana et al 2017).…”

Role of Critical Size on Adult life History Traits in Drosophila Melanogaster.

“…Early life nourishment is known to affect the adult physiology and various life-history traits in Drosophila melanogaster [1][2][3] . For example, nutrient acquisition in the form of dietary sugars (source of C) during the larval stage has contribution in egg provisioning during the early adult life of holometabolous females 4 .…”