Figure 1. Deguelin requires
fmo-4 to promote lifespan extension and improve healthspan in C. elegans.: (A) Lifespan assessment of wild-type (WT) worms exposed to DMSO control, 1 µM deguelin, 5 µM deguelin, or 10 µM deguelin (n = ~120 worms per condition, three replicate experiments performed. Significance was determined at p < 0.05 using log-rank analysis). (B) Healthspan analysis of wild-type (WT) worms exposed to DMSO control or 10 µM deguelin thrashing in a drop of M9 solution for 30 seconds on days 1 and 8 of adulthood (n = ~10 worms per condition, three replicate experiments). (C) Fluorescence intensity of
fmo-4p::mCherry transcriptional reporter worms exposed to DMSO control or 10 µM deguelin (n = ~20 worms per condition, three replicate experiments), quantified in (D). (E) Lifespan assessment of wild-type (WT) and
fmo-4 knockout (KO) worms exposed to DMSO control or 10 µM deguelin (n = ~120 worms per condition, three replicate experiments performed. Significance was determined at p < 0.05 using log-rank analysis and significant interactions between the condition of interest and genotype was determined at p < 0.01 using Cox regression analysis). (F) Healthspan analysis of wild-type (WT) and
fmo-4 knockout (KO) worms exposed to DMSO control or 10 µM deguelin thrashing in a drop of M9 solution for 30 seconds on days 1 and 8 of adulthood (n = ~10 worms per condition, three replicate experiments). (G) Lifespan assessment of wild-type (WT) and
mcu-1 knockout (KO) worms exposed to DMSO control or 10 µM deguelin (n = ~120 worms per condition, three replicate experiments performed. Significance was determined at p < 0.05 using log-rank analysis and significant interactions between condition of interest and genotype was determined at p < 0.01 using Cox regression analysis). For healthspan and imaging experiments, * denotes significant change at p < 0.05 using unpaired two-tailed t test. NS = not significant. All replicate data can be found in the Source Data files.