Counterbalance between BAG and URX neurons via guanylate cyclases controls lifespan homeostasis in C. elegans

• Published in: The EMBO journal Vol. 32; no. 11; pp. 1529 - 1542
• Main Authors: Liu, Tiewen, Cai, Dongsheng
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 29-05-2013; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Animals; C. elegans; Caenorhabditis elegans - enzymology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Carbon dioxide; Carbon Dioxide - physiology; Cell Survival; Dietary restrictions; EMBO27; EMBO37; Gene Expression Regulation, Enzymologic; Guanylate Cyclase - genetics; Guanylate Cyclase - metabolism; Homeostasis; Humans; Insulin; Life span; lifespan; Longevity; Longevity - genetics; Models, Biological; Mutation; neuron; Neurons; Neurons - enzymology; Neurons - physiology; Organ Specificity; Organisms, Genetically Modified; Oxygen; Oxygen - physiology; Signal Transduction - physiology; Worms; neuron; lifespan
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2013.75

Lifespan of
C. elegans
is affected by the nervous system; however, the underlying neural integration still remains unclear. In this work, we targeted an antagonistic neural system consisting of low‐oxygen sensing BAG neurons and high‐oxygen sensing URX neurons. While ablation of BAG neurons increases lifespan of
C. elegans
, ablation of URX neurons decreases lifespan. Genetic analysis revealed that BAG and URX neurons counterbalance each other via different guanylate cyclases (GCYs) to control lifespan balance. Lifespan‐modulating effects of GCYs in these neurons are independent of the actions from insulin/IGF‐1 signalling, germline signalling, sensory perception, or dietary restriction. Given the known gas‐sensing property of these neurons, we profiled that lifespan of
C. elegans
is promoted under moderately low oxygen (4–12%) or moderately high carbon dioxide (5%) but inhibited under high‐level oxygen (40%); however, these pro‐longevity and anti‐longevity effects are counteracted, respectively, by BAG and URX neurons via different GCYs. In conclusion, BAG and URX neurons work as a neural‐regulatory system to counterbalance each other via different GCYs to control lifespan homeostasis.
Neurons that sense low (BAG) and high oxygen (URX) decrease or increase lifespan in
C. elegans
, respectively, by regulating different guanylate cyclases and independently of pathways previously implicated in ageing.