AIMS: To study the role of hypoxia-reoxygenation and anoxia-starvation on the lifespan ofand elucidate the mechanism at molecular levels. C. elegans
BACKGROUND: Increasing evidence indicates that reactive oxygen species (ROS) act as signaling molecules that promote health. Hormesis occurs when a moderate stress level induces a beneficial adaptive response, protecting organisms against subsequent exposure to severe stress.is a widely used model organism to study aging and displays a broad hormetic ability to couple with stress. To date, only few methods are available to induce stress hormesis in. Caenorhabditis elegans C. elegans
OBJECTIVES: The objectives of this study were to explore the effects of hypoxia-reoxygenation and anoxia-starvation on the lifespan of, exploring the involvement of ROS and oxidative stress-related pathways, and examining the hormetic property of H/R. C. elegans
METHODS: Thewere cultured in hypoxic conditions (1% O) with OP50 bacteria for 24 h followed by reoxygenation (20% O) (H/R) or in anoxic conditions (0% O; 100% N) without OP50 bacteria for 24 h followed by reoxygenation (20% O) and food supplementation (A/S). Survivals were plotted and estimated for probability with Kaplan-Meier analysis. C. elegans2 2 2 2 2
RESULTS: The H/R extended the lifespan of, and H/R-pretreated worms showed improved resistance toward A/S compared to naïve worms. TheSKN-1 and DAF-16 are important oxidative stress response factors homologous to mammalian Nrf2 and FOXO3, respectively. Mutations in SKN-1 and DAF-16 blocked H/R-induced life extension. Next, H/R treatment inactivated both SKN-1 and DAF-16, as indicated by the upregulation of putative target genes of SKN-1 (and) and DAF-16 (). Moreover, pre-treatment with antioxidants (N-acetylcysteine, chlorogenic acid, and sulforaphane) reduced ROS levels and diminished the lifespan extension effect of H/R, indicating their dependency on ROS. C. elegans C. elegans C. elegans gcs-1gss-1sod-3
CONCLUSION: These results provide evidence that H/R is beneficial for lifespan and stress resistance by activating the adaptive cellular response pathway (SKN-1 and DAF-16A) toward oxidative stress.
