嗅觉 AWA 神经元功能所需的基因以依赖胰岛素/IGF 信号的方式调控秀丽隐杆线虫的寿命。
Genes required for the functions of olfactory AWA neuron regulate the longevity of Caenorhabditis elegans in an insulin/IGF signaling-dependent fashion.
机构信息
Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Department of Genetics and Developmental Biology, Southeast University Medical School, Nanjing 210009, China.
出版信息
Neurosci Bull. 2010 Apr;26(2):91-103. doi: 10.1007/s12264-010-0162-6.
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 confirm 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 influence 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 AWA 嗅觉神经元功能所需基因与胰岛素/IGF 信号在调控秀丽隐杆线虫（C. elegans）寿命中的相互作用。
方法
利用 AWA、AWC、ASE 和 AFD 感觉神经元丧失功能突变的突变体，检测寿命、咽泵吸速度、肠道自发荧光、 dauer 形成和产卵数。进行挽救实验以确认 AWA 神经元功能所需基因在调节寿命中的作用。此外，还研究了 AWA 神经元功能所需基因与胰岛素/IGF 信号之间的遗传相互作用。
结果
AWA 神经元功能所需的 odr-7、odr-2 和 odr-3 基因突变显著增加了线虫的平均寿命，并减缓了肠道自发荧光的积累。此外，这些突变与衰老过程中更高的泵吸率密切相关。然而，odr-7、odr-2 或 odr-3 的突变并未明显影响产卵数或 dauer 形成，odr-7、odr-2 和 odr-3 对寿命的调控与温度无关。相反，ASE、AWC 和 AFD 感觉神经元功能所需基因的突变并不影响线虫的寿命。此外，odr-7、odr-2 和 odr-3 在 AWA 神经元中的表达可完全或部分恢复 odr-7、odr-2 和 odr-3 突变体中改变的寿命。此外，遗传相互作用实验表明，odr-7 突变体的延长寿命可被 daf-16 突变抑制，被 daf-2 或 age-1 突变增强，而 mev-1 和 pha-4 不是 odr-7 突变体长寿命所必需的。
结论
AWA 感觉神经元功能所需的基因可在秀丽隐杆线虫中以胰岛素/IGF 信号依赖的方式调节线虫的寿命。
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