Fig. 6.

Dopamine D2 receptor antagonists and rotenone induce and extend lifespan in the DR pathway. A–B Images and quantification of fmo-2p::mCherry induction by strong drug hits under DR condition. Drugs that do not further induce fmo-2 are in red, while drugs that further induce are in gray. The DR condition (without drug treatment) is in purple. All fmo-2p::mCherry animals were synchronized to L4 stage and treated with indicated drugs under DR condition for 18 h. Worms were treated with 1-μM rotenone, 100-μM deguelin, 100-μM pinaverium bromide, 100-μM dihydrorotenone, 30-μM chlorhexidine, 100-μM trifluoperazine, 500-μM diphenyleneiodonium (DPI), 500-μM butaclamol, 100-μM methylbenzethonium, 100-μM thioridazine, and 100-μM mianserin as a control. Scale bar, 1 mm. C–F Survival curves of wild-type worms after drug treatments under DR condition. Rotenone and three DRD2 antagonists thioridazine, trifluoperazine, and butaclamol do not further extend lifespan under DR. Wild-type worms were synchronized to L4 stage, treated with 1-μM rotenone, 25-μM thioridazine, 0.1-μM trifluoperazine, or 5-μM butaclamol under DR condition, and lifespan was then measured. ***indicates P < 0.001; *indicates P < 0.05 when drug induced lifespan extension of worms under DR condition compared to fed condition (Cox regression) in C–F. P-values (log-rank test) and Cox regression analyses of lifespan curves comparisons were listed in Supplementary Table 3 by log-rank test. ****indicates P < 0.0001; **indicates P < 0.01; *indicates P < 0.05 when compared to control (Welch two-sample t-test, two-sided) in B