Fig. 5: Estradiol valerate inhibits the ISR and extends lifespan.

a Fluorescence images of atf-4P::GFP::unc-54 3′UTR reporter animals grown on NGM plates supplemented with 10 µg/mL tunicamycin (TM) and with the indicated compounds (20 µM) or 1% DMSO vehicle control (Est Val = estradiol valerate, Propa = propafenone hydrochloride, Aza = azadirachtin). Scale bar is 75 µm, n = 1. b Survival of WT worms treated with 1% DMSO (control) or 20 µM estradiol valerate from day 1 (D1), day 5 (D5), or day 10 (D10) (representative data from n = 2 independent experiments). c Representative Western blot of day 1 worms treated with 1% DMSO (control) or 20 µM estradiol valerate. Worms were incubated without (−) or with 5 mM DTT (+) for 2 h. Levels of phospho-eIF2α (Ser51) were normalized to α-tubulin (error bars represent means +SEM, one-way ANOVA Dunnett’s post hoc test, **p = 0.0044 DTT vs. DMSO; ns = not significant vs. DMSO; n = 7 independent experiments). d Survival of WT worms treated with 1% DMSO (control) or 20 µM estradiol valerate from day 1 of adulthood upon RNAi treatment targeting kin-35 or control luciferase (representative data from n = 2 independent experiments). e Survival of ppp-1 mutants and WT controls treated with 1% DMSO (control) or 20 µM estradiol valerate from day 1 of adulthood (representative data from n = 2 independent experiments). See Supplementary Dataset 1 for survival statistics. Source data are provided as a Source Data file.