A metabolic signature of long life in Caenorhabditis elegans.
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.
Fuchs
Silke
S
Division of Biology, Silwood Park Campus, Imperial College London, UK.
Bundy
Jacob G
JG
Davies
Sarah K
SK
Viney
Jonathan M
JM
Swire
Jonathan S
JS
Leroi
Armand M
AM
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D050260:Carbohydrate Metabolism / Q000235:genetics / Q000502:physiology; D005943:Gluconeogenesis / Q000235:genetics / Q000502:physiology; D006038:Glyoxylates / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D009154:Mutation; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology
D000596:Amino Acids; D029742:Caenorhabditis elegans Proteins; D006038:Glyoxylates; D007328:Insulin; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; C031150:glyoxylic acid