(583.9) Longevity Effects of DMSO-Solubilized Rapamycin and Other Compounds in y w Male Drosophila melanogaster

Poster Board Number: E328

Robin Mockett (University of South Alabama), Aaron Bearden (University of South Alabama), Amber Nobles (University of South Alabama, University of South Alabama)

This study was performed to screen a number of potentially life-extending supplements, including inhibitors of the TOR signal transduction pathway, while confirming life extension by other, previously tested compounds. This initial screen was conducted in male flies of a comparatively long-lived y w strain of D. melanogaster. A hypothesis was that reports of life extension by some compounds would be confirmed and other longevity-enhancing compounds would be identified, with optimum dosages that could be tested subsequently in males and females of multiple genotypes. The following supplements were delivered continuously throughout adult life, beginning 2 d posteclosion: rapamycin (0.1, 0.5, 1, 10, 100, 200 and 400 µM), spermidine (10 µM - 10 mM), LY294002 (100 nM - 10 µM), wortmannin, KU0063794 and PX-866-17OH (all 1 nM - 10 µM), AZD8055, PI-103 HCl and Torin 2 (all 100 pM - 10 µM), WYE-28 and WYE-132 (both 10 pM - 1 µM) and DMSO solvent (0.02-0.2%). Unexpectedly, the main finding was a strong, dose-dependent decrease in mean life span at high doses of rapamycin, ranging from a 29% decrease at 100 µM to 46% decrease at 400 µM (all P lt; 0.0005). Rapamycin had no significant effect at the lower doses. The highest dose of wortmannin (10 μM) also drastically decreased longevity (73%, P lt; 0.0005) and the highest dose of spermidine (10 mM) had a smaller adverse effect (11%, P lt; 0.0005), while the highest doses of PI-103 HCl (10 μM) and AZD8055 (10 μM), an intermediate dose of AZD8055 (0.1 μM) and the lowest dose of WYE-132 (10 pM) increased life span by 4-6% (P = 0.001 - 0.029). The other supplements had no significant effect on longevity at any dose. Possible explanations of the rapamycin result include use of a DMSO solvent in contrast to ethanol used for past studies, or storage of DMSO-solubilized rapamycin in aliquots at -20ºC; however, the DMSO solvent at the low concentrations used to dissolve the supplements had no effect on life span. Experiments are in progress to test the effects of high dose rapamycin in male and female flies of several strains, comparing ethanol and DMSO solvents, different food recipes, lighting and storage conditions. A current conclusion is that rapamycin is not universally beneficial in Drosophila and that inhibitors of various kinases at the doses studied have limited or no effect on longevity.

Support or Funding Information

This work was funded by anonymous donors.