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

BMC Biol. 2010 Jun 28;8:91. doi: 10.1186/1741-7007-8-91.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Alleles
  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Hydrogen Peroxide / metabolism
  • Insulin / metabolism*
  • Mitochondria / metabolism*
  • Mutation
  • Oxidative Stress
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Insulin
  • Hydrogen Peroxide
  • DAF-2 protein, C elegans
  • Receptor, Insulin