Figure 1. A schematic illustration presenting a model for the increased lifespan and healthspan of gcy-35(-);npr-1(-) animals. In the absence of gcy-35, the O2-sensing neurons AQR, PQR, and URX are not activated by O2. Our data suggest that GCY-31 and GCY-33 activate a HIF-1-dependent signalling pathway in which neuropeptide and neurotransmitter induce defence responses against bacteria and UV damage in remote tissues. Therefore, although the worm is in a hyperoxic environment, it can benefit from defences activated by hypoxia signalling. The question mark represents our uncertainty about the tissues/cells in which HIF-1 activity is required.