A metabolic signature of long life in Caenorhabditis elegans.
A metabolic signature of long life in Caenorhabditis elegans.
复制标题
DOI：
10.1186/1741-7007-8-14
复制
发表时间：
2010-02-10
期刊：
影响因子：
5.4
通讯作者：
Leroi AM
中科院分区：
文献类型：
--
作者：
Fuchs S;Bundy JG;Davies SK;Viney JM;Swire JS;Leroi AM
许多秀丽隐杆线虫的突变增加了寿命，许多证据表明，它们至少部分地通过新陈代谢的变化来实现这一点。然而，到目前为止，还没有系统的研究长寿突变体的代谢网络与正常蠕虫的代谢网络有何不同。代谢组学技术允许并行分析许多非靶向代谢物，现在使这成为可能。在这里，我们使用其中之一，1H核磁共振光谱，调查是什么使长寿的蠕虫代谢独特。我们研究了三类长寿的蠕虫：幼虫，成人胰岛素/IGF-1信号（IIS）缺陷突变体，和一个prevention-deficient突变。令人惊讶的是，这些表面上不同的长寿蠕虫有着共同的代谢特征，主要是碳水化合物和氨基酸代谢的变化。此外，dauer幼虫，独特的，有升高的水平的修饰氨基酸（羟脯氨酸和磷酸丝氨酸）。我们询问现有的基因表达数据，以整合功能（代谢水平）的变化与转录变化的途径水平。观察到的代谢反应可以解释在很大程度上通过上调的代谢产物和乙醛酸分流以及氨基酸catenin的变化。这些反应指出了蠕虫长寿保证的新的可能机制。在dauer幼虫中观察到的代谢变化可以通过导致细胞成分再循环的高水平自噬的存在来解释。参见相关的minireview：www.example.com
Many Caenorhabditis elegans mutations increase longevity and much evidence suggests that they do so at least partly via changes in metabolism. However, up until now there has been no systematic investigation of how the metabolic networks of long-lived mutants differ from those of normal worms. Metabolomic technologies, that permit the analysis of many untargeted metabolites in parallel, now make this possible. Here we use one of these, 1H nuclear magnetic resonance spectroscopy, to investigate what makes long-lived worms metabolically distinctive. We examined three classes of long-lived worms: dauer larvae, adult Insulin/IGF-1 signalling (IIS)-defective mutants, and a translation-defective mutant. Surprisingly, these ostensibly different long-lived worms share a common metabolic signature, dominated by shifts in carbohydrate and amino acid metabolism. In addition the dauer larvae, uniquely, had elevated levels of modified amino acids (hydroxyproline and phosphoserine). We interrogated existing gene expression data in order to integrate functional (metabolite-level) changes with transcriptional changes at a pathway level. The observed metabolic responses could be explained to a large degree by upregulation of gluconeogenesis and the glyoxylate shunt as well as changes in amino acid catabolism. These responses point to new possible mechanisms of longevity assurance in worms. The metabolic changes observed in dauer larvae can be explained by the existence of high levels of autophagy leading to recycling of cellular components. See associated minireview: http://jbiol.com/content/9/1/7
登录
查看更多内容
影响因子：
4
作者：
Behm, CA
通讯作者：
Behm, CA
影响因子：
10.5
作者：
Hamilton, B;Doug, YQ;Lee, SS
通讯作者：
Lee, SS
影响因子：
7
作者：
Griffin, TJ;Gygi, SP;Aebersold, R
通讯作者：
Aebersold, R
影响因子：
4.5
作者：
Hansen M;Hsu AL;Dillin A;Kenyon C
通讯作者：
Kenyon C
影响因子：
4.8
作者：
Fisher, Alfred L.;Page, Kathryn E.;Nash, Lindsey
通讯作者：
Nash, Lindsey