LAUSR

Abstract Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti‐inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin‐treated flies. The results identified 404 active metabolites in addition to the extended lifespan and improved healthspan in fly. There were 28 metabolites having significant changes between aspirin‐treated group and the control group, out of which 22 compounds were found to have detailed information. These compounds are reported to have important functions in energy metabolism, amino sugar metabolism, and urea metabolism, indicating that aspirin might be playing positive roles in the fly's lifespan and healthspan improvement. Because of the conservation of major longevity pathways and mechanisms in different species, the health benefits of aspirin administration could be extended to other animals and humans as well. HighlightsAspirin extends Drosophila lifespan.Aspirin enhances Drosophila healthspan.Aspirin‐treated fruit flies display alteration in 28 metabolites.Major differential metabolites are involved in energy metabolism, amino sugar metabolism, and urea metabolism.