摘要
Objective To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans （C. elegans）. Methods The mutants that had loss-of-function mutation of the genes required for AWA, AWC, ASE, and AFD sensory neurons were employed. Lifespan, the speed of pharynx pumping, the intestinal autofluorescence, the dauer formation, and the brood size were examined. Rescue experiments were performed to confrm the role of the genes required for the functions of AWA neuron in regulating lifespan. Moreover, genetic interactions between genes required for the functions of AWA neuron and insulin/ IGF signaling were investigated. Results Mutations of odr-7, odr-2, and odr-3 genes required for the functions of AWA neuron significantly increased the mean lifespan of nematodes and slowed the accumulation of intestinal autofluorescence. Besides, these mutations were closely associated with higher pumping rates during aging. However, mutation of odr-7, odr- 2, or odr-3 did not obviously affect the brood size or the dauer formation, and the regulation of longevity by odr-7, odr-2, and odr-3 was temperature-independent. In contrast, mutations of genes required for the functions of ASE, AWC, and AFD sensory neurons did not infuence the nematode lifespan. Moreover, expression of odr-7, odr-2 and odr-3 in AWA neuron could completely or largely restore the altered lifespan in odr-7, odr-2 and odr-3 mutants. Furthermore, genetic interaction assay demonstrated that the extended lifespan in odr-7 mutant could be suppressed by daf-16 mutation and enhanced by daf- 2 or age-1 mutation, whereas mev-1 and pha-4 were not required for the long lifespan of odr-7 mutant. Conclusion The genes required for the function of AWA sensory neuron could regulate the nematode longevity in an insulin/IGF signaling-dependent fashion in C. elegans.
目的研究嗅觉神经元AWA功能必需基因与胰岛素信号之间在调控秀丽线虫衰老上的关系。方法测定AWA、AWC、ASE与AFD感觉神经元的功能必需基因突变后线虫的寿命、咽泵运动速率、肠道荧光、永久性幼虫形成与后代数目的变化。此外,进行基因功能的恢复实验以确认AWA功能必需基因在调控衰老中的作用。最后,对AWA功能必需基因与胰岛素信号间在调控衰老上的遗传关系进行了分析。结果AWA功能必需基因odr-7、odr-2与odr-3突变能显著延长动物寿命,并在衰老过程中诱导产生相对于野生型更高的咽泵运动速率和更少的肠道脂褐质积累。然而,odr-7、odr-2与odr-3的基因突变并不影响线虫的后代数目与永久性幼虫的形成,且odr-7、odr-2与odr-3基因对于寿命的调控并未呈现出明显的温度依赖性。比较而言,感觉神经元ASE、AWC与AFD的功能必需基因的突变并未显著影响动物寿命。而且,在嗅觉神经元AWA表达odr-7、odr-2与odr-3基因可以完全或很大程度上恢复对应突变体的长寿表现型。进一步遗传分析表明,odr-7突变体的长寿表现型可被daf-16基因突变所抑制,被daf-2或age-1基因突变所增强,而mev-1与pha-4基因突变对此并不产生影响。结论嗅觉神经元AWA功能必需基因以胰岛素信号依赖的方式调控秀丽线虫的衰老。
基金
supported by the National Natural Science Foundation of China (No. 30771113,30870810)
the Program for New Century Excellent Talents in University
