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


RESULTS
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.


CONCLUSIONS
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.
Brys
Kristel
K
Department of Biology, Ghent University, K L Ledeganckstraat 35, Ghent B-9000, Belgium. Bart.Braeckman@UGent.be.
Castelein
Natascha
N
Matthijssens
Filip
F
Vanfleteren
Jacques R
JR
Braeckman
Bart P
BP
D000375:Aging / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D006861:Hydrogen Peroxide; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin