Fig. 3: Preventing age-related decline in PT causes accelerated aging and shortens lifespan and healthspan.
From: Early-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling
a Immunoblots of phospho-S6K and S6K. Actin was used as a loading control. n = 3; one-way ANOVA with Tukey’s post-hoc test. b Puromycin incorporation in daGS > UAS-S6KTE flies (±RU486 after day 2). n = 3/group; two-way ANOVA with Sidak correction. c Experimental scheme to block age-related decline in PT; 200 µM RU486, 200 µM RU486 + 1 µM CHX, or vehicle given to daughterless-GeneSwitch GAL4 (daGS)>UAS-S6KTE flies after day 2 (the PT peak). d S6KTE overexpression after day 2 shortens lifespan (: −41.8%, male: −45.6%; % change in median lifespan), but concurrent CHX treatment restores lifespan comparable to that of controls. Each sex: n = 250/group; log-rank test. e S6KTE overexpression after day 2 impairs locomotion at day 40. n = 200 female/group; two-way ANOVA with Sidak correction. f S6KTE overexpression after day 2 causes premature defects in gut-barrier integrity in Smurf assays. n = 250 female/group; two-way ANOVA with Sidak correction. g S6KTE overexpression after day 2 impairs cognition in olfaction aversion training at day 40. n = 200 female/group; Chi-square test. h (Left) representative images of eggs laid on vials at day 30 by daGS > UAS-S6KTE flies and daGS > w1118 (control) flies treated with ± RU486 after day 2. (Middle) S6KTE overexpression after day 2 causes faster age-related decline in egg production. n = 100/group; two-way ANOVA with Sidak correction. (Right) Area under the curve was calculated to determine lifetime egg production. S6KTE overexpression after day 2 impairs lifetime egg production. Two-tailed Student’s t-test. Data shown as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. male healthspan data in Supplementary Fig. 4. Source data are provided as a Source Data file.
