Individuals are exposed to thousands of toxic chemicals on a daily basis. Many toxic chemicals produce reactive oxygen species (ROS), which can greatly contribute to protein modification and the accumulation of protein carbonyl groups; often used as an indicator of cellular aging. The antioxidant response to toxic chemicals involves activation of the antioxidant response elements (AREs)/Electrophile Response Elements (EpREs), located in the promoter regions of the genes of antioxidant and phase two enzymes, and regulated by the nuclear factor-erythroid 2 subunit-related transcription factors (Nrf1, Nrf2, and Nrf3). Activation of the AREs/EpREs, in particular by Nrf1, in response to polybrominated diphenyl ether (PBDE) flame retardants was investigated. Protein damage as a result of PBDE treatment, as assessed by carbonyl assays, and cellular aging, as assessed by β-galactosidase assays, was also examined. We found that PDBE-induced oxidative stress causes activation of AREs/EpREs. We also found that PDBE-induced oxidative stress further promotes accumulation of carbonyl groups on proteins and general cellular aging. The results provide insight into how the antioxidant response is activated by PDBEs, how they damage proteins through ROS and how damage by these compounds is related to advanced cellular aging. As a significant proportion of our population will reach their senior years in the very near future, an understanding of how toxic chemicals influence the aging process is required.