Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans

Department of Biology, Ghent University, K L Ledeganckstraat 35, Ghent B-9000, Belgium. .
BMC Biology (Impact Factor: 7.98). 06/2010; 8(1):91. DOI: 10.1186/1741-7007-8-91
Source: PubMed


The gene daf-2 encodes the single insulin/insulin growth factor-1-like receptor of Caenorhabditis elegans. The reduction-of-function allele e1370 induces several metabolic alterations and doubles lifespan.
We found that the e1370 mutation alters aerobic energy production substantially. In wild-type worms the abundance of key mitochondrial proteins declines with age, accompanied by a dramatic decrease in energy production, although the mitochondrial mass, inferred from the mitochondrial DNA copy number, remains unaltered. In contrast, the age-dependent decrease of both key mitochondrial proteins and bioenergetic competence is considerably attenuated in daf-2(e1370) adult animals. The increase in daf-2(e1370) mitochondrial competence is associated with a higher membrane potential and increased reactive oxygen species production, but with little damage to mitochondrial protein or DNA. Together these results point to a higher energetic efficiency of daf-2(e1370) animals.
We conclude that low daf-2 function alters the overall rate of ageing by a yet unidentified mechanism with an indirect protective effect on mitochondrial function.

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Available from: Filip Matthijssens, Oct 01, 2015
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    • "Age-related changes in mitochondrial metabolism are also well documented. Early life stages often display more anaerobic metabolism and spherical morphologies, and older individuals typically show signs of mitochondrial dysfunction although these effects are frequently tissue specific (Braeckman et al., 2002; Brand et al., 2004; Brys et al., 2007, 2010; Dillin et al., 2002; Hebert et al., 2010; Jansen and de Boer, 1998; Knudsen and Green, 2004; Meyer et al., 2007; Tsang and Lemire, 2003; Tsang et al., 2001; Yasuda et al., 2006). How reduced aerobic mitochondrial function will influence the effect of mitochondrial toxicants is not certain. "
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    Toxicological Sciences 04/2013; 134(1). DOI:10.1093/toxsci/kft102 · 3.85 Impact Factor
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    • "Faced with hyperoxidative stress, organisms rely on antioxidant mechanisms to neutralize accumulating ROS. One method for microorganisms to prevent significant oxidation-induced damage is to generate antioxidant substances, such as vitamin E, oxalic acid, ascorbic acid and antioxidant enzymes such as superoxide dismutase [36], catalase, and peroxidase as well [32]. As the exudate that appeared on the surface of the sclerotia comprised oxalic acid [37]–[38] and antioxidant enzymes [31], these antioxidant molecules might play a part in resisting the hyperoxidant state. "
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    • "In the left panel, asterisks denote bands that are not clearly decreased by skn-1 RNAi, in contrast to 85 kD SKN-1 itself. (B) Partial purification was achieved by spinning down the mito pellet (mito), as indicated by the presence of remaining mitochondrial marker, PDHE1 (Greiss et al., 2008; Li et al., 2011; Brys et al., 2010), in the cytosolic fraction (cyto), but the mitochondria fraction lacks the cytoplasmic marker GAPDH. (C) Arrowhead indicates remaining PDHE1 that was not removed by stripping. "
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