Fig. 5: Early-life exposure to Cyrene is sufficient to extend lifespan.

To determine the timing requirements for Cyrene’s geroprotective effects, lifespan assays were performed under temporally restricted exposure paradigms as outlined in (A). In the “Cyrene exposure begins” paradigm, animals were treated with 1% Cyrene starting at defined life stages (L1, young adult [YA], Day 3, Day 5, Day 8, or Day 12) and maintained on treatment thereafter. In the “Cyrene exposure ends” paradigm, worms were exposed to Cyrene from L1 and transferred to untreated plates at the same respective timepoints. A separate group received only transient exposure (48 hours from YA to Day 3). B The maximum lifespan was observed when Cyrene treatment was initiated at L1 or young adulthood with diminishing effects on lifespan when administered to older worms. Cyrene treatment at day 8 and beyond resulted in decreased lifespan. For worms treated with 1% Cyrene beginning at L1, the maximum lifespan was achieved when exposure lasted until day 12 of adulthood with diminishing effects with shorter durations of exposure. C A brief, early-life exposure (48 h; YA to Day 3) was sufficient to induce significant and lasting lifespan extension almost comparable to lifelong Cyrene treatment. Combined these results suggest that early life exposure to Cyrene is crucial for its lifespan extending activity. Error bars represent the standard error of the mean (SEM). Sample sizes (n-values) are indicated within each bar. Statistical analyses were performed using one-way ANOVA with Dunnet’s multiple comparisons test for (B), and log-rank test for (C). *p < 0.05, ****p < 0.0001.