Diapause-associated metabolic traits reiterated in long-lived daf-2 mutants in the nematode Caenorhabditis elegans

Diapause-associated metabolic traits reiterated in long-lived daf-2 mutants in the nematode Caenorhabditis elegans
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DOI:
10.1016/j.mad.2006.01.006
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发表时间:
2006-05-01
影响因子:
5.3
通讯作者:
Gems, D
Gems, D
中科院分区:
医学3区
文献类型:
--
作者:
McElwee, JJ;Schuster, E;Gems, D

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秀丽隐杆线虫幼虫的寿命大大超过成虫。Dauer形成和成年衰老都受胰岛素/IGF-I信号转导(IIS)调节。减少IIS,例如通过daf-2胰岛素/IGF-I受体基因突变,增加成年寿命。这可能反映了成年人长寿保证过程的错误表达。由于IIS在代谢调节中起着核心作用,因此dauer幼虫和daf-2成虫共享的代谢改变代表了寿命决定的候选机制。我们对dauers和daf-2突变体成虫的转录谱数据进行了详细的比较,重点是代谢途径基因的表达。我们的研究结果意味着上调dauers和daf-2突变体成人的胚胎发育,乙醛酸途径的活动,和海藻糖的生物合成。柠檬酸循环和线粒体呼吸链的下调发生在dauers,但不是daf-2成人。然而,F,ATP酶抑制剂在两者中均上调,这意味着在线粒体应激的条件下增强的稳态。总的来说,这些数据意味着脂肪转化为碳水化合物的增加,以及daf-2突变成年人ATP储备的保护,表明能量可用性增加的状态。我们假设,这燃料增加体细胞的维护活动,如一次性索马理论所建议的。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The longevity of the Caenorhabditis elegans diapausal dauer larva greatly exceeds that of the adult. Dauer formation and adult ageing are both regulated by insulin/IGF-I signaling (IIS). Reduced IIS, e.g. by mutation of the daf-2 insulin/IGF-I receptor gene, increases adult lifespan. This may reflect mis-expression in the adult of dauer longevity-assurance processes. Since IIS plays a central role in the regulation of metabolism, metabolic alterations shared by dauer larvae and daf-2 adults represent candidate mechanisms for lifespan determination. We have conducted a detailed comparison of transcript profile data from dauers and daf-2 mutant adults, focusing on expression of metabolic pathway genes. Our results imply up-regulation in both dauers and daf-2 mutant adults of gluconeogenesis, glyoxylate pathway activity, and trehalose biosynthesis. Downregulation of the citric acid cycle and mitochondrial respiratory chain occurs in dauers, but not daf-2 adults. However, the F, ATPase inhibitor was up-regulated in both, implying enhanced homeostasis in conditions where mitochondria are stressed. Overall, the data implies increased conversion of fat to carbohydrate, and conservation of ATP stocks in daf-2 mutant adults, suggesting a state of increased energy availability. We postulate that this fuels increased somatic maintenance activity, as suggested by the disposable soma theory. (c) 2006 Elsevier Ireland Ltd. All rights reserved.