A metabolic signature of long life in Caenorhabditis elegans
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RESEARCH ARTICLE
Open Access
A metabolic signature of long life in Caenorhabditis elegans Silke Fuchs1,2†, Jacob G Bundy3†, Sarah K Davies1, Jonathan M Viney4, Jonathan S Swire5, Armand M Leroi1*
Abstract Background: 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. Results: 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. Conclusions: 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
Background The nematode Caenorhabditis elegans normally has a life-span of about three weeks. The dauer larva, however, lives for up to eight times longer [1]. In addition, mutations in scores of genes have been identified that increase longevity. These genes have been grouped into several pathways including the Insulin/Insulin-Like signalling pathway (IIS) [2-6], the dietary restriction pathway [7,8] and the translation control pathway [9], but how they regulate ageing individually and together is still obscure. What is certain, however, is that each of them influences the metabolism of the worm in some fashion. This has been shown by the discovery that particular longevity pathways control, or at least interact
* Correspondence: [email protected] † Contributed equally 1 Division of Biology, Silwood Park Campus, Imperial College London, SL5 7PY, UK
with, key regulators of metabolism [10-13] as well as many metabolic enzymes [14-22]. Despite these advances, our understanding of how altered metabolism influences longevity in worms, indeed, if it does so at all, remains very incomplete. In part, this is because attention has focused almost exclusively on the genes that control metabolism rather
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