We investigated the possible formation of combined toxicity from Ca/Cd exposure on nematode lifespan. Ca exposure at concentrations more than 1.56 mM significantly reduced lifespan, accelerated aging-related declines, and induced severe stress response in wild-type nematodes. Combined Ca (25 mM)/Cd (200 microM) exposure decreased the lifespans compared to Cd (200 microM) exposure; whereas no lifespan differences were found between Ca (1.56 mM)/Cd (200 microM) exposure and Cd (200 microM) exposure. Combined Ca (25 mM)/Cd (200 microM) exposure caused a more significant induction of hsp-16.2::gfp expression, and a more severe increase in oxidative damage than Cd (200 microM) exposure. Moreover, mutation of mev-1, encoding a subunit of succinate dehydrogenase cytochrome b, enhanced the combined Ca/Cd toxicity on lifespan. Furthermore, mutation of daf-16, encoding a fork-head-family transcription factor, enhanced the combined Ca/Cd toxicity on lifespan, and mutation of daf-2, encoding an insulin receptor-like protein, alleviated the combined Ca/Cd toxicity on lifespan.