Prolonged exposure to triadimenol at environmentally relevant concentration accelerates aging process in Caenorhabditis elegans via DAF-16

Triadimenol is a widely used agricultural antifungal which is commonly detected in the environment due to its stable property. Triadimenol is able to disrupt genomic stability and modulate function of several transcription factors, yet the prolonged exposure of triadimenol and its age-related toxicity effects remain elucidated. This study utilized Caenorhabditis elegans (C. elegans) to study the toxicity of triadimenol on aging and the underlying mechanisms. The results showed that 0.1 % ETOH (ethanol) as solvent control did not affect the locomotive behaviors, reproduction, and growth in C. elegans. Therefore, 0.1 % ETOH was used as control throughout this study. Triadimenol at environmentally relevant concentrations (3, 30, 300 μg/L) significantly affected worm’s growth, and reduced the total brood size at 30 and 300 μg/L. Additionally, prolonged exposure to 3, 30, 300 μg/L triadimenol significantly inhibited locomotive behaviors of C. elegans in a dose-dependent manner. Moreover, under the most effective concentration, 300 μg/L triadimenol reduced C. elegans mean (17.3 days), median (18 days), and maximum (29 days) lifespan at 15, 15, 25 days, respectively. Further evidence showed that triadimenol (300 μg/L) accelerated the decline in pharyngeal pumping rate and the increase in defecation cycles, implying physiological aging. In addition, triadimenol (300 μg/L) significantly increased lipofuscin accumulation in day- 4, 8 adulthood, but did not significantly increase lipid peroxidation until day 8 adulthood. Similarly, triadimenol (300 μg/L) did not significantly elevate internal ROS (reactive oxidative species) levels such as H2O2 and O2•‒ until day 8 adulthood. By using the transgenic GFP strains, we found that triadimenol (300 μg/L) triggered DAF-16 translocation from cytosol into nucleus in C. elegans, suggesting that triadimenol exerted oxidative stress on C. elegans. In contrast, triadimenol did not affect SKN-1 translocation, suggesting that triadimenol toxicity in C. elegans is not SKN-1 mediated. In conclusion, this study demonstrated that prolonged exposure to triadimenol at environmentally relevant concentration resulted in oxidative stress and accelerated aging process in C. elegans via DAF-16.