Oxygen deprivation is a key component of ischemic damage associated with cardiovascular disease and traumatic blood loss. These health issues will be better understood if the mechanisms that prevent oxygen-deprivation induced cell death are elucidated. Previously we showed that wild-type C. elegans survive one day of anoxia(<.001 kPa O2)but cannot survive three days of anoxia; in these experiments the animals were raised at 20C, maintained on OP50 bacteria and exposed to anoxia at 20C. Adult animals, grown at 20C, and then exposed to one day of anoxia and heat stress (28C) cannot survive indicating that the combination of thermal stress and anoxia decreases viability. Our recent findings demonstrate that preconditioning at 25C of wild-type animals will induce prolonged anoxia survival (three days). This thermal preconditioning effect is enhanced when animals are grown on RNAi control media,suggesting a synergetic affect between RNAi control media and thermal preconditioning. To determine if,in addition to thermal stress, the stress associated with dietary restriction will induce a preconditioning effect on animals exposed to anoxia,we used the dietary restriction mutant
eat-2(
ad1116);we found that dietary restriction also induces anoxia survival. These results indicate that preconditioning environments can enhance anoxia survival in wild-type animals. Additionally, genetic mutations elicit a long-term anoxia survival phenotype. Several
daf-2 alleles as well as mutations in
glp-1 (
glp-1(
q158),
glp-1(
e2141)) induce a long-term anoxia survival phenotype (20C). We are interested in identifying the molecular changes in
glp-1 and
daf-2 mutant animals that lead to a long-term anoxia survival phenotype. Both
glp-1 and
daf-2 mutations are known to have a longevity phenotype and the pathways involved with such are well understood. Therefore, we used RNAi to screen through several known genes required for the longevity phenotype in either
glp-1 or
daf-2 animals; these experiments will allow us to determine genetic pathways and genes required for anoxia survival and further elucidate components of signaling pathways required for longevity and/or stress resistance. We found that
aak-2,the catalytic subunit of AMP activated protein kinase (AMPK) is required for the anoxia survival phenotype in
daf-2(
e1370),25C preconditioned N2,and in a DAF-16 dependent fashion,
glp-1(
e2141);the other AMPK catalytic subunit (
aak-1) is not required,suggesting that
aak-1 and
aak-2 have distinct functions. Together,our findings indicate that stress and longevity pathways (Insulin-like, notch, TOR and AMPK signaling) overlap and may exhibit cross talk that is modulated depending upon the specific stress presented to the organism.