How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life Decrepitude

Cell Rep. 2017 Apr 18;19(3):441-450. doi: 10.1016/j.celrep.2017.03.062.

Abstract

The goal of aging research is to extend healthy, active life. For decades, C. elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1) receptor mutants have served as a model for extended lifespan and youthfulness. However, a recent report suggested that their longevity is associated with an undesirable phenotype: a disproportionately long period of decrepitude at the end of life. In the human population, such an outcome would be a burden to society, bringing into question the relevance of daf-2 mutants as a model for life extension. However, here we report that, following an extended period of movement, daf-2 mutants survive longer in a decrepit state because of a beneficial trait: they are resistant to colonization of the digestive tract by dietary bacteria, a condition that leads to premature death in the wild-type and prevents their manifestation of decrepitude. If bacterial colonization is prevented, then daf-2 mutants lead both chronologically and proportionately healthier lives relative to the wild-type.

Keywords: IGF-1; aging; daf-2; healthspan; lifespan; mortality; pathogenesis.

MeSH terms

  • Aging / genetics*
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / microbiology
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism
  • Colony Count, Microbial
  • Escherichia coli / growth & development
  • Mutation / genetics*
  • Risk Factors

Substances

  • Caenorhabditis elegans Proteins