Date Published: June 14, 2017
Publisher: John Wiley and Sons Inc.
Author(s): Jennifer M.A. Tullet, James W. Green, Catherine Au, Alexandre Benedetto, Maximillian A. Thompson, Emily Clark, Ann F. Gilliat, Adelaide Young, Kathrin Schmeisser, David Gems.
In C. elegans, the skn‐1 gene encodes a transcription factor that resembles mammalian Nrf2 and activates a detoxification response. skn‐1 promotes resistance to oxidative stress (Oxr) and also increases lifespan, and it has been suggested that the former causes the latter, consistent with the theory that oxidative damage causes aging. Here, we report that effects of SKN‐1 on Oxr and longevity can be dissociated. We also establish that skn‐1 expression can be activated by the DAF‐16/FoxO transcription factor, another central regulator of growth, metabolism, and aging. Notably, skn‐1 is required for Oxr but not increased lifespan resulting from over‐expression of DAF‐16; concomitantly, DAF‐16 over‐expression rescues the short lifespan of skn‐1 mutants but not their hypersensitivity to oxidative stress. These results suggest that SKN‐1 promotes longevity by a mechanism other than protection against oxidative damage.
SKN‐1 is the C. elegans functional ortholog of the mammalian Nrf transcription factors. It protects against stress such that deletion or over‐expression of skn‐1 results in animals that are hypersensitive or resistant, respectively, to stress (Blackwell et al., 2015). skn‐1 also protects against aging: loss of skn‐1 shortens lifespan and skn‐1 over‐expression or gain‐of‐function usually increases lifespan (Blackwell et al., 2015; Tang & Choe, 2015). As stress resistance and increased lifespan (Age) are often correlated, one possibility is that protection against stress causes longer life (Ristow & Schmeisser, 2011).
Some strains were provided by the Caenorhabditis Genetics Center, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This work was supported by a Wellcome Trust Strategic Award (CA, AFG, DG and JMAT) and a Royal Society Research grant (JMAT).