Diet-dependent, beneficial and adverse effects of rapamycin on life span of Drosophila melanogaster.

Rapamycin supplementation has been reported to extend life spans in numerous species, including Drosophila melanogaster, but a recent study in this laboratory revealed a marked life-shortening effect in y w male flies. The experiments reported here were performed to characterize conditions under which rapamycin could extend or shorten life spans in five fly strains. On a cornmeal/torula yeast-based medium, rapamycin extended life in one experiment, had no effect in six and was harmful in 19. On a nutrient-rich brewer's yeast medium favored by 4/5 strains for egg-laying, rapamycin was beneficial in eight, neutral in 14 and not significantly harmful in any experiment. Effects on median life span ranged from -51.3 to + 5.4% and were sex- and strain-specific, with limited differences for rapamycin dissolved in ethanol vs dimethylsulfoxide and for mated vs unmated flies. The life-shortening effect in y w males on the torula medium was greater when food was provided within 1-3 days after preparation vs 4-9 days, but similar under constant darkness vs 12 h light:12 h darkness. As an antifungal agent, rapamycin was expected to rescue shortened life spans when acids and methyl 4-hydroxybenzoate were omitted from the media, but removing these preservatives did not diminish the life span. Rapamycin was not consistently aversive for egg-laying, except in Dahomey flies at 200 µM. It prevented development to adulthood at 10-200 µM and delayed it at 0.1-1 µM concentrations. The results confirm the adverse effects of rapamycin during development and demonstrate its potential to switch between beneficial and harmful effects on adult life span depending on other components of the diet.