Polystyrene nanoplastics are associated with telomere-associated alterations and senescence-related changes in intestinal epithelial cells involving PPARα-POT1 regulation.

Nanoplastics have emerged as important environmental contaminants with potential risks to animal and human health; however, their effects on intestinal epithelial cells remain unclear. In this study, polystyrene nanoplastics (PS) were used to investigate cytotoxic mechanisms in porcine intestinal epithelial cells(IPI-2I). PS exposure was associated with oxidative stress, as evidenced by elevated reactive oxygen species levels, altered oxidative stress-related indicators, and mitochondrial structural alterations. Increased γ-H2AX expression suggested activation of DNA damage responses. Transcriptomic analysis revealed enrichment of pathways associated with oxidative stress and telomere maintenance. PS exposure was also associated with telomere-associated alterations, including altered expression of shelterin complex proteins (TERF1, TERF2, and POT1), decreased telomerase activity, and shortened relative telomere length. In addition, PS treatment was associated with senescence-related phenotypes, including increased p53 and p21 expression and a higher proportion of SA-β-gal-positive cells. Bioinformatic and experimental analyses suggested a potential association between PPARα and POT1 regulation under PS exposure conditions. Chromatin immunoprecipitation-qPCR analysis suggested that PPARα could associate with the POT1 promoter region, and this enrichment was reduced after PS exposure. Collectively, the present findings suggest that PS exposure is associated with oxidative stress, DNA damage, telomere-associated alterations, and senescence-related changes in intestinal epithelial cells. In addition, PPARα may participate in telomere-associated cellular responses under PS exposure conditions.