Genetic variation in glia–neuron signalling modulates ageing rate



Time: 14:00-15:30, December 13, 2017

Venue: B323 Medical Science Building 


Speaker: Professor Shiqing Cai, Principle Investigator, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, CAS


Host: Professor Guangshuo Guo, Tsinghua McGovern Institute for Brain Research


Title: Genetic variation in glia–neuron signalling modulates ageing rate



The rate and severity of behavioural and cognitive decline in ageing population are remarkably different among individuals. Despite great interest in studying individual variation in ageing rate to identify factors that control healthy ageing, so far no such factor has been found. Here we discover a genetic basis for natural variation in ageing rate in Caenorhabditis elegans. We found that natural C. elegans isolates showed diverse lifespan and age-related decline in mating virility, pharyngeal pumping, and locomotion. Polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and a neuropeptide receptor gene npr-28 regulated age-related deterioration of mating virility and pharyngeal pumping, but not the lifespan. Selective deletion of rgba-1 in glia, but not neurons or intestinal cells, prevented deterioration of mating virility. RGBA-1 activated NPR-28 signaling and loss-of-function npr-28 mutations prevented mating virility deterioration. 

The latter effect was not additive to that induced by rgba-1 mutation, and was abolished by expressing NPR-28 in serotonergic or dopaminergic neurons. The ageing rate reduction by down-regulating RGBA-1/NPR-28 signaling required SIR-2.1-dependent activation of mitochondrial unfolded protein response, a pathway modulating ageing. Population genetic analysis showed that rgba-1 and npr-28 might be subjected to recent selective sweep. Furthermore, rgba-1 is a novel gene because no RGBA-1 homologue was found in other nematode species. Thus, evolution in the ageing rate may have been affect by multiple factors, such as the emergence of new genes, natural selection, and the interaction among genetic loci. Together, our work suggests that natural variation in neuropeptide-mediated glia-neuron signaling modulates ageing rate.




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