Rapamycin Supplementation: Effect on Longevity in Drosophila melanogaster

Abstract

Target of rapamycin (TOR) regulates a number of cellular responses, including autophagy. The purpose of this study was to investigate the effect on life span of supplementation with rapamycin dissolved in either dimethylsulfoxide (DMSO) or ethanol, in male and female flies of three strains of Drosophila melanogaster: Oregon R, w1118, and y w. The hypothesis was that longevity would be decreased regardless of strain, sex or solvent, consistent with an unpublished prior study using y w males in this laboratory, or alternatively that it would be increased as in publications from other laboratories. Flies were exposed to food supplemented with 200 µM rapamycin dissolved in one of the two solvents before being mixed into a standard agar‐yeast‐cornmeal‐sucrose medium. Supplementation was continuous beginning 2 d posteclosion. The mean life span of Oregon R females was diminished by rapamycin in both ethanol and DMSO solvents, by 17% and 13%, respectively (P < 0.0005). Oregon R males also exhibited a shortened mean life span, which was significant in DMSO (8%, P = 0.008) but not ethanol (3%, P = 0.9). In contrast, w1118 female flies had a 4% increase in mean life span with rapamycin dissolved in ethanol (P < 0.0005) but not DMSO (1% increase, P = 0.2). Rapamycin decreased life span in w1118 males, but the effect was significant only in DMSO (22%, P = 0.002), not ethanol (10%, P = 0.6). It decreased longevity significantly in y wflies of both sexes on both solvents, by 9% in females and 7‐12% in males (all P < 0.0005 except male/DMSO P = 0.04). Notably, the life spans of control flies differed significantly between the solvents, being longer with ethanol for y w of both sexes and longer with DMSO for Oregon R males and w1118 males. In conclusion, these results show that effects of rapamycin on life span of Drosophila are sex‐, strain‐ and solvent‐dependent.