Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans

Background:preventing germline stem cell proliferation extends lifespan in nematodes and flies. so far,studies on germline-longevity signaling have focused on daf-16/foxo and daf-12/vdr. here,we report on nhr-80/hnf4,a nuclear receptor that specifically mediates longevity induced by depletion of the germ line through a mechanism that implicates fatty acid monodesaturation.methods and findings:nhr-80/hnf4 is induced in animals lacking a germ line and is specifically required for their extended longevity. overexpressing nhr-80/hnf4 increases the lifespan of germline-less animals. this lifespan extension can occur in the absence of daf-16/foxo but requires the presence of the nuclear receptor daf-12/vdr. we show that the fatty acid desaturase,fat-6/scd1,is a key target of nhr-80/hnf4 and promotes germline-longevity by desaturating stearic acid to oleic acid (oa). we find that nhr-80/hnf4 and oa must work in concert to promote longevity.conclusions:taken together,our data indicate that the nhr-80 pathway participates in the mechanism of longevity extension through depletion of the germ line. we identify fat-6 and oa as essential downstream elements although other targets must also be present. thus,nhr-80 links fatty acid desaturation to lifespan extension through germline ablation in a daf-16/foxo independent manner. © 2011 goudeau et al.