Beta-guanidinopropionic acid does not extend Drosophila lifespan

Activation of AMP activated protein kinase (AMPK) signaling has been demonstrated to extend lifespan and improve healthspan across multiple species. This suggests pharmaceutical approaches to increase AMPK hold the potential to modify the aging process and promote healthy aging. Beta-guanidinopropionic acid (GPA) is a naturally occurring metabolite structurally similar to creatine. GPA is capable of activating AMPK signaling in mammalian models via competitive inhibition of cytosolic creatine kinase. A previous report suggested that dietary GPA supplementation increased lifespan in Drosophila through its effect on AMPK signaling and regulation of autophagy. However, studies in Caenorhabditis have found no beneficial effect of this compound on worm lifespan and that GPA may actually diminish lifespan in at least one Caenorhabditis species. To confirm previous reports of increased longevity in Drosophila, we tested a wide range of GPA concentrations on lifespan and healthspan in both male and female W¹¹¹⁸ flies. We report here that GPA does not extend lifespan in Drosophila as previously reported. Moreover, high doses of GPA are detrimental to Drosophila lifespan and stress resistance in male flies. These results suggest the lack of a robust effect of GPA on Drosophila lifespan and highlight the importance of replication studies within the field of aging.