Ebselen is an organoselenium compound that has activity similar to glutathione peroxidase, and is able to neutralize free radicals and protect the cell’s components from oxidative stress. Due to ebselen’s potent antioxidant activity, we hypothesized that it may have biological activity in preventing the onset of aging phenotypes and possibly extending lifespan. Using the tractable model organism C. elegans, our lab has demonstrated that ebselen extends lifespan of C. elegans in a dose-dependent manner, slows development, delays the onset of egg-laying, and increased youthful locomotion in aged worms chronically exposed to the drug. To elucidate the mechanism behind ebselen’s ability to protect against oxidative stress and slow development, insulin receptor-deficient (daf-2) and Nrf2-deficient (skn-1) animals were exposed to ebselen, and their phenotypes were scored. DAF-2-deficient animals have been shown to be resistant to oxidative stress and experience a delay in development. However, ebselen-treated daf-2 animals did not experience an additive or synergistic effect on oxidative stress resistance or development. SKN-1 is a transcription factor with activity that protects against oxidative stress. Interestingly, ebselen requires SKN-1 activity to protect C. elegans against oxidative stress and to slow development at 56 hours post hatching.

Deducing the mechanism by which ebselen delays maturation and protects against oxidative stress in C. elegans

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.