Journal
AGING CELL
Volume 12, Issue 3, Pages 508-517Publisher
WILEY
DOI: 10.1111/acel.12076
Keywords
arsenite; Caenorhabditis elegans; hormesis; lifespan; mitochondria; mitohormesis; oxidative stress; reactive oxygen species; ROS; toxicology
Categories
Funding
- NIH National Center for Research Resources (NCRR)
- German Ministry for Education and Research (Bundesministerium fur Bildung und Forschung) [BMBF 0315581]
- German Research Association (Deutsche Forschungsgemeinschaft, DFG) [RI 1976/3-1]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available