Curcumin (diferuloylmethane), a pharmacologically active substance derived from turmeric, exhibits anti-inflammatory, anticarcinogenic, and antioxidant properties. We examined the modulation of oxidative-stress resistance and associated regulatory mechanisms by curcumin in a Caenorhabditis elegans model. Our results showed that curcumin-treated wild-type C. elegans exhibited increased survival during juglone-induced oxidative stress compared with the control treatment. In addition, curcumin reduced the levels of intracellular reactive oxygen species in C. elegans. Moreover, curcumin induced the expression of the gst-4 and hsp-16.2 stress response genes. Lastly, our findings from the mechanistic study in this investigation suggest that the antioxidative effect of curcumin is mediated via regulation of age-1, akt-1, pdk-1, osr-1, unc-43, sek-1, skn-1, sir-2.1, and mev-1. Our study elucidates the diverse modes of action and signaling pathways that underlie the antioxidant activity exhibited by curcumin in vivo. [ABSTRACT FROM AUTHOR]