Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension
Authors: Schmeisser, S; Schmeisser, K; Weimer, S; Groth, M; Priebe, S; Fazius, E; Kuhlow, D; Pick, D; Einax, JW; Guthke, R; Platzer, M; Zarse, K; Ristow, M
HERO ID: 1519026
Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects . . .
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 life span. Taken together, low-dose arsenite extends lifespan, providing evidence for non-linear dose-response characteristics of toxin-mediated stress resistance and longevity in a multicellular organism. © 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.