Caenorhabditis elegans lifespan extension caused by treatment with an orally active ROS-generator is dependent on DAF-16 and SIR-2.1.
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.
Heidler
Tanja
T
Department of Food and Nutrition, Molecular Nutrition Unit, Technical University of Munich, Am Forum 5, Freising, Germany.
Hartwig
Kai
K
Daniel
Hannelore
H
Wenzel
Uwe
U
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051858:Forkhead Transcription Factors; D017353:Gene Deletion; D006360:Heat-Shock Proteins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008136:Longevity / Q000187:drug effects*; D023421:Models, Animal; D009285:Naphthoquinones / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D004791:Enzyme Inhibitors; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins; C005134:juglone