Aging is a natural process, however it may bring undesirable alterations to the organisms. One of the many mechanisms by which age can cause disorders is linked to oxidative stress. Many genetic and pharmacological therapies that improve lifespan also can regulate cytoprotective mechanisms. Conversely, cytoprotective pathways may lead to resistance to many stressors. In this context, new synthetic compounds that might modulate cytoprotective machinery can be promising candidates to pre-clinical tests to treat age-associated diseases. The Nrf2 homologue,
skn-1, plays an important cytoprotective role under oxidative stress, readily accumulating at the nucleus, increasing the expression of superoxide dismutases and glutathione-s-transferases, among others.
daf-16, another important cytoprotective gene that plays role in C. elegans longevity and stress resistance, which may or may not act concomitantly to
skn-1. Our research aimed to elucidate the underlying mechanisms by which a new compound, 4-aryl-telluroquinoline, improves lifespan of stressed C. elegans. We exposed L1 worms to 1microM of the compound during 30 minutes. The experiment was conducted in liquid and free-bacteria media. We induced oxidative stress in our strains (EU31 [
zu135], CL2166 [dvIs19], RB1823 [
ok2108], GA480 [
gk257]; [
tm760], CF1553 [muIs84]) by using paraquat right after compound exposure. We measured fluorescence levels by using GFP-tagged strains, and also ROS levels by H2DCF-DA. Repeated measures and One-way ANOVA were applied, and a p<0.05 was considered as significant. We verified that the compound was not able to restore paraquat-induced reduced lifespan in the absence of
skn-1 and
gst-4. Lifespan extension caused by the compound treatment persisted in the absence of
daf-16,
sod-2,3, and
gcs-1. We also verified that ROS levels were diminished in worms that were post-treated with the compound, when compared to paraquat group, whereas the same effect was not observed inskn-1 mutants. SOD-3::GFP and GST-4::GFP fluorescence were increased right after the treatment, however their levels did not persist after 48h. We suggest that 4-aryl-telluroquinoline may regulate
skn-1 downstream pathway by up-regulating GST-4 and SOD-3 levels, thus reducing the amount of ROS generated by paraquat. Even playing a possible role in ROS detoxification,
sod-2,3, does not show itself as a necessary component to lifespan improvement.
gst-4 is possibly playing a role in detoxification of compromised biomolecules following the oxidative damage induced by paraquat, and this action seems to be necessary to lifespan improvement.