A metabolomics approach identifies -Sitosterol to increases Longevity in adult Drosophila melanogaster. Matthew J. Laye, Kisha Barrett, Pankaj Kapahi. Buck Institute, Novato, CA.

   The restriction of specific nutrients without causing malnutrition, dietary restriction (DR), is a robust nutritional intervention capable of increasing lifespan in organisms ranging from yeast to mammals. However, DR also leads to changes in specific metabolites that might be critical for the increased lifespan and associated phenotypes that accompany DR. Thus, we sought to determine whether feeding metabolites that increase when Drosophila melanogaster are fed a DR diet of 0.5% Yeast diet while fed a 5% Yeast nutrient rich diet (referred to as AL from here) was sufficient to increase lifespan. As expected DR decreased the concentration of amino acids and increased the concentration of AMP and nicotinic acid, demonstrating efficacy of the DR. Interestingly, -sitosterol, a sterol metabolite with documented beneficial metabolic effects, increased in the DR condition relative to the AL. -sitosterol increased lifespan of flies fed an AL diet, but not a DR. Furthermore, feeding -sitosterol increased metabolism indicated by increased VO2 and VCO2, which was consistent with a decreased resistance to starvation on AL, but not DR diet. However, the increased general metabolism was not associated with increased levels of activity, AMPK phosphorylation, or mRNA of several genes important for fatty acid metabolism. In conclusion, the sterol -sitosterol has beneficial effects on lifespan in flies fed a nutrient rich diet through an unknown mechanism.