Diet altered rapamycin’s effect on fly lifespan

Diet altered rapamycin’s effect on fly lifespan

On August 8, researchers reported in GeroScience that they had compared five laboratory strains of fruit flies on two diets. At the same dose, median lifespan, the age reached by half of the flies in a group, ranged from +5.4% to −51.3%. In the wDah strain, the drug slightly extended lifespan on a brewer’s yeast diet but shortened it on a diet containing cornmeal and torula yeast.

Rapamycin inhibits TORC1, a cell-signaling system that links nutrient availability to cell growth and protein production. In a 2010 study, 50–400 μM rapamycin extended the lifespan of adult flies. The 200 μM dose produced the largest increase in median lifespan among female wDah flies. The authors of the new paper selected this dose to investigate why previous results had differed.

The authors tested the effects of the solvent, light exposure, food freshness, sex, and genotype in turn. They compared ethanol with DMSO, which was used as the drug solvent. These conditions changed the magnitude of the response, but the largest difference emerged when the diets were compared directly. In males from another laboratory strain, w1118, rapamycin reduced median lifespan by 51.3% on a diet containing cornmeal, torula yeast, and sugar.

The brewer’s yeast diet contained more yeast and sugar. On this diet, rapamycin increased median lifespan by 2–5% in females from several strains. In the wDah strain, changing the diet while keeping the dose constant reversed the direction of the result, from +2–5% to −17–26%. The authors obtained both results in the same experiment.

“The composition of the food medium was the main factor that altered rapamycin’s effect on lifespan,” the authors write.

The authors tested whether rapamycin’s antifungal activity accounted for the difference by removing preservatives from the food. The difference between the diets remained. They propose that, on the nutrient-rich brewer’s yeast diet, TORC1 inhibition acts like moderate calorie restriction. On the torula diet, it may restrict nutrient use more severely.