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