Dietary restriction by growth in axenic medium induces discrete changes in the transcriptional output of genes involved in energy metabolism in Caenorhabditis elegans

Abstract

Dietary restriction increases life span in a wide range of species, including the nematode worm Caenorhabditis elegans. The mechanism by which it does so remains largely unknown, although it is commonly thought that a reduction of reactive oxygen species (ROS) plays a pivotal role. More specifically, for C. elegans, it has been proposed that food restriction reduces energy expenditure, possibly in conjunction with an anaerobic shift in energy production, with consequent reduction in the formation of ROS. We have measured differential transcript abundance of 49 genes known to play roles in energy metabolism in axenic culture medium, which causes a nutritional deficit and leads to a substantial increase of life span. We found no evidence for a reduction in metabolic rate or a shift to anaerobic metabolism in axenic culture. Major changes induced by growth in axenic medium include down-regulation of lipid degradation and up-regulation of glyoxylate cycle activity glyceroneogenesis and, possibly, gluconeogenesis. The activities determined in worm extracts for pyruvate kinase, phosphoenolpyruvate carboxykinase and isocitrate lyase followed a similar trend. We conclude that growth in axenic culture is marked by a general up-regulation of replenishing pathways.

SIR-2.1 integrates metabolic homeostasis with the reproductive neuromuscular excitability in early aging male Caenorhabditis elegans

“…SIR-2.1’s role in regulating metabolic processes has not been well described in C. elegans hermaphrodites, and scarcely in males. Therefore, we compared the expression levels of 55 genes involved in multiple metabolic processes including: glycolysis, gluconeogenesis/glyceroneogenesis, citrate acid cycle, glyoxylate cycle, fatty acid metabolism and electron transport chain (ETC)/oxidative phosphorylation (OXPHOS) (Castelein et al, 2008) between age-matched sir-2.1(0) and wild-type males. Out of the 55 genes we surveyed, 17 showed statistically significant changes (Figure 5); the information for all the genes is tabulated in the Supplementary file 1.

10.7554/eLife.01730.015Figure 5. sir-2.1(0) males have altered expression of metabolic genes.Relative mRNA expression level of genes involved in metabolic processes such as glycolysis ( A ), TCA cycle ( B ), fatty acid oxidation( C ), Gluconeogenesis/glyceroneogenesis/lipid synthesis ( D ), Glyoxylate cycle ( E ), and ETC ( F ) in 2-day-old wild type, 1-day-old, and 2-day-old sir-2.1(0) males relative to 1-day-old wild type.

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LC–MS Proteomics Analysis of the Insulin/IGF-1-DeficientCaenorhabditis elegans daf-2(e1370)Mutant Reveals Extensive Restructuring of Intermediary Metabolism

“…The enzymatic activities were assayed spectrophotometrically against the appropriate blanks at 25 °C in microtiter plate wells using an Infinite M200 multiplate reader (Tecan, Männedorf, Switzerland). Isocitrate lyase, pyruvate kinase, aconitase, and phosphenolpyruvate carboxykinase activities were assayed as described previously by Castelein et al 58 and references therein. 6-Phosphogluconic dehydrogenase activity was assayed according to the method of Bergmeyer et al 59 following the manufacturer’s instructions (Sigma no.…”

Chronological Aging in Saccharomyces cerevisiae

“…We do not have an answer yet. However, gene expression data suggest that both glyceroneogenesis and gluconeogenesis are up-regulated in calorie restricted C. elegans (Castelein et al 2008). Furthermore, an anti-aging role for a metabolic switch to gluconeogenesis was originally hypothesized based on gene expression profile data obtained from calorie restricted mice (Lee et al 1999) and is supported by preliminary results showing that transgenic mice overexpressing the cytosolic form of phosphoenolpyruvate carboxykinase in the skeletal muscle are long-lived (Hakimi et al 2007).…”