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RNA helicase aquarius (EC (Intron-binding protein of 160 kDa) (IBP160) [KIAA0560]


Synergism between soluble guanylate cyclase signaling and neuropeptides extends lifespan in the nematode Caenorhabditis elegans.

Oxygen (O ) homeostasis is important for all aerobic animals. However, the manner by which O sensing and homeostasis contribute to lifespan regulation is poorly understood. Here, we use the nematode Caenorhabditis elegans to address this question. We demonstrate that a loss-of-function mutation in the neuropeptide receptor gene npr-1 and a deletion mutation in the atypical soluble guanylate cyclase gcy-35 O sensor interact synergistically to extend worm lifespan. The function of npr-1 and gcy-35 in the O -sensing neurons AQR, PQR, and URX shortens the lifespan of the worm. By contrast, the activity of the atypical soluble guanylate cyclase O sensor gcy-33 in these neurons is crucial for lifespan extension. In addition to AQR, PQR, and URX, we show that the O -sensing neuron BAG and the interneuron RIA are also important for the lifespan lengthening. Neuropeptide processing by the proprotein convertase EGL-3 is essential for lifespan extension, suggesting that the synergistic effect of joint loss of function of gcy-35 and npr-1 is mediated through neuropeptide signal transduction. The extended lifespan is regulated by hypoxia and insulin signaling pathways, mediated by the transcription factors HIF-1 and DAF-16. Moreover, reactive oxygen species (ROS) appear to play an important function in lifespan lengthening. As HIF-1 and DAF-16 activities are modulated by ROS, we speculate that joint loss of function of gcy-35 and npr-1 extends lifespan through ROS signaling.

MeSH Terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Food
  • Gene Expression Regulation
  • Guanylate Cyclase
  • Immunity, Innate
  • Interneurons
  • Longevity
  • Mutation
  • Neuropeptides
  • Neurotransmitter Agents
  • Oxidation-Reduction
  • Oxygen
  • Paraquat
  • Reactive Oxygen Species
  • Receptors, Neuropeptide Y
  • Signal Transduction
  • Stress, Physiological
  • Temperature
  • Transcription, Genetic


Caenorhabditis elegans

  • NPR-1
  • lifespan
  • oxygen sensing
  • reactive oxygen species
  • soluble guanylate cyclase