AQR

RNA helicase aquarius (EC 3.6.4.13) (Intron-binding protein of 160 kDa) (IBP160) [KIAA0560]

Publications

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

PubMed

Full text

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

Keywords

Caenorhabditis elegans

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