• Open Access

Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension

Authors

  • Sebastian Schmeisser,

    1. Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
    2. Leibniz Graduate School of Aging, Leibniz Institute for Age Research, Fritz-Lipmann-Institute, Jena, Germany
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  • Kathrin Schmeisser,

    1. Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
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  • Sandra Weimer,

    1. Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
    2. Energy Metabolism Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach/Zürich, Switzerland
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  • Marco Groth,

    1. Genome Analysis Group, Leibniz Institute for Age Research, Fritz-Lipmann-Institute, Jena, Germany
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  • Steffen Priebe,

    1. Systems Biology and Bioinformatics Group, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany
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  • Eugen Fazius,

    1. Systems Biology and Bioinformatics Group, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany
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  • Doreen Kuhlow,

    1. Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
    2. Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
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  • Denis Pick,

    1. Department of Environmental Analysis, Institute of Inorganic and Analytical Chemistry, University of Jena, Jena, Germany
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  • Jürgen W. Einax,

    1. Department of Environmental Analysis, Institute of Inorganic and Analytical Chemistry, University of Jena, Jena, Germany
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  • Reinhard Guthke,

    1. Systems Biology and Bioinformatics Group, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany
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  • Matthias Platzer,

    1. Genome Analysis Group, Leibniz Institute for Age Research, Fritz-Lipmann-Institute, Jena, Germany
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  • Kim Zarse,

    1. Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
    2. Energy Metabolism Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach/Zürich, Switzerland
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  • Michael Ristow

    Corresponding author
    1. Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
    2. Energy Metabolism Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach/Zürich, Switzerland
    • Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
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Correspondence

Michael Ristow, Energy Metabolism Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach/Zürich, CH 8603, Switzerland. Tel.: +41-446557428; fax: +41-446557206; e-mail: michael-ristow@ethz.ch

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.

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