Continuous and discontinuous multi-generational disturbances of tetrabromobisphenol A on longevity in Caenorhabditis elegans

Tetrabromobisphenol A (TBBPA) is one of the most prevalently used brominated flame retardants. Due to its persistence, it is predominantly found in environmental matrices and has the potential to generate multi-generational toxicity. However, knowledge of its adaptive response or long-term residual effect in multi-generations, and molecular mechanisms remain understudied. In the current study, the model animal nematode Caenorhabditis elegans (C. elegans) was exposed to TBBPA at environmentally realistic concentrations (0.1-1000 μg L⁻¹) for four consecutive generations (G₀ to G₃). Degenerative age-related multiple endpoints including lifespan, locomotion behaviors, growth, reproduction, oxidative stress-related biochemical responses, cell apoptosis, and stress related gene expressions were assessed in the continuous exposure generations (G₀ and G₃) and the discontinuously exposed generations (T₃ and T'₃). The results showed that changes in degenerative age-related response monitored four generations varied in direction and magnitude depending on the TBBPA concentrations, and the response intensify ranked as G₀ > T'₃/G₃ > T₃. TBBPA at 1 μg L⁻¹ dosage was detected as the lowest observed effect concentration in multi-biomarkers. The underlying mechanism of aging phenotypes was that reactive oxygen species accumulation led to cell apoptosis regulated by gene ape-1, and confirmed catalase enzyme and superoxide dismutase activity played a crucial role in the detoxification process of TBBPA at the molecular level. This study provided insights into the underlying mechanism of TBBPA-interfered longevity and its environmental multi-generational potential risks.