Genetic variation in glia-neuron signalling modulates ageing rate.
Genetic variation in glia-neuron signalling modulates ageing rate.
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胶质神经元信号传导的遗传变异调节衰老速度。
DOI：
10.1038/nature24463
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发表时间：
2017
期刊：
影响因子：
64.8
通讯作者：
Cai Shi-Qing
中科院分区：
文献类型：
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作者：
Yin Jiang-An;Gao Ge;Liu Xi-Juan;Hao Zi-Qian;Li Kai;Kang Xin-Lei;Li Hong;Shan Yuan-Hong;Hu Wen-Li;Li Hai-Peng;Cai Shi-Qing
老龄人口行为衰退的速度在个人之间差异很大。尽管相当大的兴趣，在研究自然变化的衰老率，以确定控制健康的老龄化的因素，没有这样的因素尚未发现。在这里，我们报告的遗传基础上的变化，在衰老率inCaushabditis秀丽隐杆线虫。我们发现C. elegansisolates显示出不同的寿命和年龄相关的男性生殖力、咽泵和运动能力的下降。一种新的肽编码基因，rgba-1和神经肽受体基因pr-28的DNA多态性影响了蠕虫交配行为与年龄相关的下降速度;这两个基因可能受到了最近的选择性扫描。神经胶质细胞衍生的RGBA-1激活NPR-28信号传导，其作用于多巴胺能和多巴胺能神经元以加速行为恶化。这种信号传导涉及线粒体未折叠蛋白反应的SIR-2.1依赖性激活，这是一种调节衰老的途径。因此，神经肽介导的胶质神经元信号传导的自然变化调节了C。优美的
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 inCaenorhabditis elegans. We find thatC. elegansisolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, namedregulatory-gene-for-behavioural-ageing-1(rgba-1), and the neuropeptide receptor genenpr-28influence 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 inC. elegans.