Open AccessThe SKN ‐1/Nrf2 transcription factor can protect against oxidative stress and increase lifespan in C. elegans by distinct mechanisms
Author(s) -
Tullet Jennifer M.A.,
Green James W.,
Au Catherine,
Benedetto Alexandre,
Thompson Maximillian A.,
Clark Emily,
Gilliat Ann F.,
Young Adelaide,
Schmeisser Kathrin,
Gems David
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12627
Subject(s) - transcription factor , biology , oxidative stress , caenorhabditis elegans , microbiology and biotechnology , longevity , oxidative phosphorylation , mutant , regulator , transcription (linguistics) , gene , genetics , biochemistry , linguistics , philosophy
Summary 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.