Fig. 4: Transient elevation in PT during early-adulthood triggers age-related proteostatic dysfunction and drives aging via juvenile hormone.
From: Early-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling
Early-adulthood=day 0–10. a Early-adulthood 1 µM CHX prevents age-related buildup of insoluble ubiquitinated proteins (IUP). n = 3/group; two-way ANOVA with Sidak correction. b No age-related buildup of IUP in long-lived chico homozygotes. S6KTE overexpression (day 0–4) causes age-related buildup of IUP in chico homozygotes. n = 3/group; two-way ANOVA with Sidak correction. c Volcano plots of proteomic analyses comparing Triton X-100 soluble fractions from day 2 vs. day 0 flies (top) and day 2 flies (±CHX, bottom). n = 8/group; two-tailed Student’s t-test, FDR < 0.05. d Volcano plot of proteomic analysis comparing Triton X-100 insoluble fractions from day 50 flies (±CHX (day 0–10)). n = 8/group; two-tailed Student’s t-test, FDR < 0.05. e (Left) Juvenile hormone levels measured via GC-MS normalized to wet mass in day 0 flies and day 2 flies treated with vehicle or CHX. n = 25/group. (Right) Early-adulthood CHX prevents buildup of IUP at day 50; however, early-adulthood CHX+Met (methoprene, 25 µg/mL) causes buildup of IUP at day 50 just like controls. n = 3/group; two-way ANOVA with Sidak correction. f Early-adulthood Met (25 µg/mL) largely abolishes CHX-mediated longevity (female: + 6.1% vs. + 36.7%, male: + 7.7% vs. + 34.6%; % change in median lifespan, p < 0.0001). Early-adulthood Met alone shortens lifespan (p < 0.0001), but the effect is smaller than what we observe under simultaneous CHX treatment (proportional hazard analysis in Supplementary Fig. 6). Whole adulthood Met shortens lifespan (p < 0.0001). Each sex: n = 250/group; log-rank test. g, Lifespan extension by early-adulthood CHX is diminished under CA (corpora allata) ablation (female: + 7.9% vs. + 41.5%, male: + 9.7% vs. + 42.5%). Control 1=Aug21-GAL4 > w1118; Control 2 = w1118 > UAS-NiPp1; CA ablated=Aug21-GAL4 > UAS-NiPp1. Each sex: n = 250/group; log-rank test. Proportional hazard analysis in Supplementary Fig. 6. Data shown as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Source data are provided as a Source Data file.
