A metabolic signature of long life in Caenorhabditis elegans

Abstract

BackgroundMany 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.ResultsWe 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.ConclusionsThe 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

Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

“…6). Because elevated respiration under physiologically normal conditions often leads to a reduction in ROS production (31), this indeed implies a direct involvement of metformin in the observed increase in ROS.…”

“…Although some evidence points toward BCAAs as a metabolic signature of long life in C. elegans insulin receptor mutants (31,32), other studies have causally linked BCAAs to the development of insulin resistance, diabetes (33), and neuropathologies (34). Interestingly, BCAAs, leucine in particular, are potent activators of the target of rapamycin (TOR) kinase.…”

Radiation hormesis and radioadaptive response in Drosophila melanogaster flies with different genetic backgrounds: the role of cellular stress-resistance mechanisms

“…ATM, ATR, and p53 genes regulate lifespan, and deficiency of these genes leads to premature senescence (Symphorien and Woodruff 2003;Maier et al 2004;Moskalev 2007;Shen and Tower 2009;Chen et al 2010). Recently, it has been determined that autophagy also affects resistance to oxidative and starvation stresses, and longevity of living organisms (Slavikova et al 2005;Bassham et al 2006;Kaushik and Cuervo 2006;Rose et al 2006;Juhász et al 2007;Swanlund et al 2008;Kang and Avery 2009;Fuchs et al 2010;Madeo et al 2010). It is possible that stress resistance and longevity factors SIRT1, mTOR, FOXO3, NF-jB, and p53 can regulate the aging process via autophagy (Salminen and Kaarniranta 2009).…”

Tissue-specific down-regulation of S-adenosyl-homocysteine via suppression of dAhcyL1/dAhcyL2 extends health span and life span in Drosophila

“…In addition, analyses of changes associated with dietary restriction (DR) that slows down the aging process have also demonstrated dramatic changes in the expression of different metabolic genes (Pletcher et al 2002). Similarly, studies in worms (Fuchs et al 2010), mice (Tomas-Loba et al 2013), and humans (Yu et al 2012) have documented changes in the metabolome during the aging process. Recently, untargeted metabolomics analysis in flies (Hoffman et al 2014) has suggested that DR might reverse age-dependent metabolic reprogramming at the tissue (Laye et al 2015) and whole-organism (Avanesov et al 2014) levels.…”