Fig. 6. NHR-49 is required for GR-induced longevity.
a Lifespan showing that NHR-49 is required for GR-induced longevity. nhr-49 (nr2041) completely abolished GR-induced longevity (P = 1, P value determined by two-tailed Student’s t test). Results from one of three independent experiments are shown. b Lifespans showing that the effects of aak-2 and nhr-49 mutation on lifespan are not additive. The mean lifespan of nhr-49;aak-2 is comparable to that of nhr-49 animals (P = 1, P value determined by two-tailed Student’s t test). Results from one of three biological independent experiments are shown. c, d Lifespans showing that nhr-49 gain-of-function (gof) mutations, et7 (c) and et13 (d), in aak-2(ok524) animals gain the GR-mediated longevity (P < 1.0 × 10−10, P value determined by two-tailed Student’s t test). Results from one of three biological independent experiments are shown. e, f Lifespans showing that nhr-49gof transgenes, et7 (e) and et13 (f), rescued GR induced longevity in aak-2 mutants (P < 1.0 × 10−10, P value determined by two-tailed Student’s t test). Results from representative experiments are shown with additional repeats. g, h Lifespans showing that neither neuronal nor intestinal nhr-49 RNAi reduced the lifespan extension by GR diets (P < 1.0 × 10−10, Student’s t test). Tissue-specific RNAi animals are used for neuronal nhr-49 RNAi knockdown (g) and intestinal nhr-49 RNAi knockdown (h). Results from representative experiments are shown with additional repeats. i, j Lifespans showing that restoring NHR-49 to either neuron or intestine fully restored the lifespan extension by GR in nhr-49 mutants (P < 1.0 × 10−10, P value determined by two-tailed Student’s t test). The lifespans of nhr-49(nr2041) expressing NHR-49 in the indicated tissue are shown; pan-neuronal nhr-49 (i) and intestinal nhr-49 (j). Results from one of three independent experiments are shown. k Fat store of animals feeding AL vs. GR diets. Fixed worms are stained with Nile red dye. Intensity of posterior parts of intestine are quantified as fat contents (dotted boxes) using ImageJ software (***P < 0.001, ****P < 0.0001, P value determined by two-tailed Student’s t test). Error bars indicate standard error of mean (SEM). Results from representative experiments are shown with additional repeats. (n ≥ 18 for each condition). l Lifespan showing that Δ9 desaturases are implicated in GR-induced longevity. Lifespan extension by GR diets are significantly reduced in fat-5(tm420); fat-7(wa36); fat-6(RNAi) animals. Results from one of three independent experiments are shown. Source data are provided as a Source Data file.