, Volume 10, Issue 5, pp 859-876
Date: 20 Feb 2014

Metabolomic changes in Caenorhabditis elegans lifespan mutants as evident from GC–EI–MS and GC–APCI–TOF–MS profiling

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Lifespan mutants of the nematode Caenorhabditis elegans are a much studied aging model, however, aging-related changes at the metabolome level remain largely unexplored. To identify metabolic features connected to mitochondrial dysfunction, a hallmark of aging and age-related disease, we analyzed a short-lived mitochondrial mutant (mev-1(kn1)), a long-lived mutant with enhanced cellular maintenance (ife-2(ok306)) and the novel double mutant ife-2(ok306);mev-1(kn1) which is normal-lived, possibly through attenuation of the metabolic mev-1 phenotype. Metabolomic analysis involved coupled gas chromatography–mass spectrometry with electron ionization (GC–EI–MS) and, in addition, recently introduced GC with soft atmospheric pressure chemical ionization coupled to time-of-flight mass spectrometry (GC–APCI–TOF–MS) to yield complementary mass spectrometric information for enhanced metabolite annotation. Multivariate analysis allowed distinction of mev-1 and ife-2 mutants from the wild type, while suggesting still another, distinct metabolic phenotype for the ife-2;mev-1 double mutant. In mev-1(kn1), disturbed energy metabolism was indicated by upset TCA cycle homeostasis, elevated glycolytic substrate and lactic acid levels as well as depletion of free amino acids pools. Surprisingly, these mitochondrially related changes were retained in the ife-2;mev-1 mutant, as were highly elevated levels of the dipeptide glycylproline indicative of increased collagen catabolism. However, the double mutant reverted mev-1(kn1) changes in uric acid and long-chain fatty alcohol metabolism, two pathways connected to the peroxisomal compartment. Our results are in line with recent evidence for a critical role of this organelle in aging and demonstrate the usefulness of non-targeted metabolomics approaches for detecting complex metabolic changes in the study of mitochondrial dysfunction.