A metabolic signature of long life in Caenorhabditis elegans

• Published in: BMC biology Vol. 8; no. 1; p. 14
• Main Authors: Fuchs, Silke, Bundy, Jacob G, Davies, Sarah K, Viney, Jonathan M, Swire, Jonathan S, Leroi, Armand M
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10-02-2010; BioMed Central; BMC
• Subjects: Amino acid metabolism; Amino Acids - metabolism; Animals; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - physiology; Carbohydrate Metabolism - genetics; Carbohydrate Metabolism - physiology; Gene expression; Gene mutations; Genetic aspects; Gluconeogenesis - genetics; Gluconeogenesis - physiology; Glyoxylates - metabolism; Insulin - genetics; Insulin - metabolism; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Larva - genetics; Larva - growth & development; Larva - metabolism; Longevity; Longevity - genetics; Longevity - physiology; Magnetic Resonance Spectroscopy; Metabolites; Metabonomic analysis; Models, Biological; Mutation; Physiological aspects; Receptor, Insulin - genetics; Receptor, Insulin - physiology; Research article; Spectrum analysis; Studies
• ISSN: 1741-7007; 1741-7007
• DOI: 10.1186/1741-7007-8-14

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.