Genetic variation in glia–neuron signalling modulates ageing rate

Jiang-An Yin, Ge Gao, Xi-Juan Liu, Zi-Qian Hao, Kai Li, Xin-Lei Kang, Hong Li, Yuan-Hong Shan, Wen-Li Hu, Hai-Peng Li and Shi-Qing Cai ()
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Jiang-An Yin: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
Ge Gao: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
Xi-Juan Liu: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
Zi-Qian Hao: University of Chinese Academy of Sciences
Kai Li: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
Xin-Lei Kang: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences
Hong Li: Core Facility of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Yuan-Hong Shan: Core Facility Center of the Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
Wen-Li Hu: Core Facility Center of the Institute of Plant Physiology and Ecology, Chinese Academy of Sciences
Hai-Peng Li: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shi-Qing Cai: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences

Nature, 2017, vol. 551, issue 7679, 198-203

Abstract: Abstract The rate of behavioural decline in the ageing population is remarkably variable among individuals. Despite the considerable interest in studying natural variation in ageing rate to identify factors that control healthy ageing, no such factor has yet been found. Here we report a genetic basis for variation in ageing rates in Caenorhabditis elegans. We find that C. elegans isolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline of worm mating behaviour; these two genes might have been subjected to recent selective sweeps. Glia-derived RGBA-1 activates NPR-28 signalling, which acts in serotonergic and dopaminergic neurons to accelerate behavioural deterioration. This signalling involves the SIR-2.1-dependent activation of the mitochondrial unfolded protein response, a pathway that modulates ageing. Thus, natural variation in neuropeptide-mediated glia–neuron signalling modulates the rate of ageing in C. elegans.

Date: 2017
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DOI: 10.1038/nature24463

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