Mitochondrial hormesis links low‐dose arsenite exposure to lifespan extension

Aging Cell

Sebastian Schmeisser²  Kathrin Schmeisser²  Sandra Weimer⁵  Marco Groth¹  Steffen Priebe³  Eugen Fazius³  Doreen Kuhlow²  Denis Pick⁴  Jürgen W. Einax⁴  Reinhard Guthke³  Matthias Platzer¹  Kim Zarse² 

[1] Genome Analysis Group, Leibniz Institute for Age Research, Fritz-Lipmann-Institute, Jena, Germany;Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany;Systems Biology and Bioinformatics Group, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany;Department of Environmental Analysis, Institute of Inorganic and Analytical Chemistry, University of Jena, Jena, Germany;Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany

关键词: arsenite;    Caenorhabditis elegans;    hormesis;    lifespan;    mitochondria;    mitohormesis;    oxidative stress;    reactive oxygen species;    ROS;    toxicology;   

DOI  :  10.1111/acel.12076

来源: Wiley

【 摘 要 】

Summary

Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects on viability even at lowest concentrations. By contrast and unlike higher concentrations, we here find that exposure to low-dose arsenite promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose arsenite promotes resistance against thermal and chemical stressors and extends lifespan of this metazoan, whereas higher concentrations reduce longevity. While arsenite causes a transient increase in reactive oxygen species (ROS) levels in C. elegans, co-exposure to ROS scavengers prevents the lifespan-extending capabilities of arsenite, indicating that transiently increased ROS levels act as transducers of arsenite effects on lifespan, a process known as mitohormesis. This requires two transcription factors, namely DAF-16 and SKN-1, which employ the metallothionein MTL-2 as well as the mitochondrial transporter TIN-9.1 to extend lifespan. Taken together, low-dose arsenite extends lifespan, providing evidence for nonlinear dose-response characteristics of toxin-mediated stress resistance and longevity in a multicellular organism.

【 授权许可】

Unknown   
© 2013 John Wiley & Sons Ltd and the Anatomical Society