Chronic exposure to triadimenol at environmentally relevant concentration adversely affects aging biomarkers in Caenorhabditis elegans associated with insulin/IGF-1 signaling pathway

Triadimenol, an agricultural fungicide, is an emerging environmental concern due to its wide usage, detection in the environment, and its chemical persistency. Triadimenol has been found to disrupt endocrine signaling and alter function of several transcription factors, yet its age-related toxicity effects remain unclear. This study used Caenorhabditis elegans as an in vivo model organism to elucidate the age-related effects of triadimenol and its underlying mechanisms. The results showed that chronic exposure to triadimenol at environmentally relevant concentrations (3, 30, and 300 μg/L) adversely affected several toxicity endpoints including growth, total brood size, and locomotive behaviors. In addition, triadimenol (300 μg/L) significantly reduced the mean lifespan of wild-type N2 C. elegans from 17.9 to 16 days. Chronic exposure to triadimenol (300 μg/L) also significantly affected age-related behavioral changes, with a decreased pharyngeal pumping rate and an increased defecation cycle. Moreover, an increased accumulation of aging biomarkers including lipofuscin, lipid peroxidation, and reactive oxygen species (H2O2 and O2 −) level upon chronic triadimenol exposure was observed in aged worms. Furthermore, chronic triadimenol exposure increased the transcriptional factor DAF-16 nuclear localization. Finally, mutation of daf-2, age-1, pdk-1, akt-1, or akt-2 restored the accumulation of lipofuscin in aged worms upon chronic triadimenol exposure, while mutation of daf-16 led to more enhanced lipofuscin accumulation. Therefore, the insulin/IGF-1 signaling pathway may serve as an important molecular basis for triadimenol induced aging declines in C. elegans.