Caenorhabditis elegans lifespan extension caused by treatment with an orally active ROS-generator is dependent on DAF-16 and SIR-2.1

Biogerontology. 2010 Apr;11(2):183-95. doi: 10.1007/s10522-009-9239-x. Epub 2009 Jul 14.

Abstract

In Caenorhabditis elegans pretreatment with juglone, a generator of reactive oxygen species (ROS) provides a subsequently increased ROS-resistance. We investigated whether juglone at low or high concentrations when provided via the oral route in a liquid axenic medium affects normal lifespan of C. elegans. High juglone concentrations led to premature death, low concentrations were tolerated well and caused a prolongation of lifespan. Lifespan extension under moderate oxidative stress was associated with increased expression of small heat-shock protein HSP-16.2, enhanced glutathione levels, and nuclear translocation of DAF-16. Silencing or deletion of DAF-16 prevented the juglone-induced adaptations. RNA-interference for SIR-2.1 had the same effects as the deletion of DAF-16 but did not affect nuclear accumulation of DAF-16. Our studies demonstrate that DAF-16- and SIR-2.1-dependent alterations in gene expression after a ROS challenge lead to a lifespan extension in C. elegans as long as the stressor concentration does not exceed the saturable protective capacity.

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Forkhead Transcription Factors
  • Gene Deletion
  • Heat-Shock Proteins / metabolism
  • Kaplan-Meier Estimate
  • Longevity / drug effects*
  • Models, Animal
  • Naphthoquinones / pharmacology*
  • Oxidative Stress / physiology
  • RNA Interference
  • Reactive Oxygen Species / metabolism*
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Enzyme Inhibitors
  • Forkhead Transcription Factors
  • Heat-Shock Proteins
  • Naphthoquinones
  • Reactive Oxygen Species
  • Transcription Factors
  • daf-16 protein, C elegans
  • SIR-2.1 protein, C elegans
  • Sirtuins
  • juglone