Insulin or insulin like signaling (IIS) pathway is a crucial pathway in Caenorhabditis elegans associated with mediating longevity, and stress resistance. Regulators of G protein signaling (RGS) also modulate stress resistance and longevity in multiple in vitro and in vivo models. However, the mechanism underlying RGS mediating stress resistance and longevity remains largely unclear. Here we report that
rgs-1, an important member of rgs family, is a novel modulator of IIS pathway in C. elegans. We found that the loss of
rgs-1 dramatically promoted paraquat resistance in C. elegans. Further genetic analyses demonstrated that
rgs-1 acted downstream of
daf-2 and upstream of
age-1,
pdk-1,
daf-16. Instead of affecting those IIS-associated genes in transcriptional process, loss of
rgs-1 promoted DAF-16's nucleus translocation and subset genes' expression in paraquat-induced oxidative status. By this way,
rgs-1 mutant worms exhibited lower ROS damage and longer survival time than wild type worms when both exposed to paraquat. Other than paraquat exposure,
rgs-1 mutant also promoted lifespan and cadmium resistance relying on
daf-16. As rgs is evolutionarily conserved, our findings open a new insight into rgs family and its role in paraquat-induced oxidative stress and longevity in C. elegans or even mammals.