title: Metabolic Youth in Middle Age: Predicting Aging in Caenorhabditis elegans Using Metabolomics.
abstract: Many mutations and allelic variants are known that influence the rate at which animals age, but when in life do such variants diverge from normal patterns of aging? Is this divergence visible in their physiologies? To investigate these questions, we have used (1)H NMR spectroscopy to study how the metabolome of the nematode Caenorhabditis elegans changes as it grows older. We identify a series of metabolic changes that, collectively, predict the age of wild-type worms. We then show that long-lived mutant daf-2(m41) worms are metabolically youthful compared to wild-type worms, but that this relative youth only appears in middle age. Finally, we show that metabolic age predicts the timing and magnitude of differences in age-specific mortality between these strains. Thus, the future mortality of these two genotypes can be predicted long before most of the worms die.
authors.affiliation: Department of Life Sciences and ‡Department of Surgery and Cancer, Imperial College London , Sir Alexander Fleming Building, London SW7 2AZ, U.K.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Davies
authors.affiliation: Department of Life Sciences and ‡Department of Surgery and Cancer, Imperial College London , Sir Alexander Fleming Building, London SW7 2AZ, U.K.
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Bundy
authors.affiliation: Department of Life Sciences and ‡Department of Surgery and Cancer, Imperial College London , Sir Alexander Fleming Building, London SW7 2AZ, U.K.
authors.forename: Armand M
authors.initials: AM
authors.lastname: Leroi
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005838:Genotype; D016014:Linear Models; D008136:Longevity / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D009154:Mutation; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D014199:Trehalose / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D029742:Caenorhabditis elegans Proteins; D014199:Trehalose; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin
keywords: daf-2; metabolomics; mortality; trehalose