Neophytadiene attenuates nano-polystyrene-elicited premature senescence of human lung epithelial cells correlating with RNA methylation

Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants that deposit in the deep respiratory tract and gain entry into cells. Yet, the precise mechanisms by which they induce cellular senescence, notably via RNA methylation, remain unclear. Although neophytadiene (NPT), as a food and medicine homology (FMH) agent, displays anti-inflammatory, antioxidant, and antipyretic effects, its protective role against oxidative injury in lung epithelial cells and the underlying mechanism await further clarification. A cellular senescence model was generated in human bronchial epithelial BEAS-2B cells using PS-NPs (0.04 and 0.08 mg/mL) as inducers, with NPT (15 μmol/L) administered as intervention to assess its regulatory impact on RNA methylation during premature senescence. Continuous exposure for 48 h induced a typical premature senescent phenotype, marked by higher β-galactosidase activity, ROS overproduction, S-phase arrest, and increased senescence-associated secretory phenotypes. NPT intervention efficiently attenuated these effects. Concomitantly, distinct alterations emerged in the expression profiles of RNA methylation regulators and the total m6A and m7G levels. Notably, expression of m6A writers, erasers, and hnRNPC, together with m7G writer METTL1 and NCBP2, was substantially elevated, which was effectively reversed by NPT intervention. RNA-seq further revealed predominant enrichment of DEGs from PS-NPs vs control comparison in senescence, p53, and DNA replication pathways, whereas DEGs from PS-NPs vs NPT contrast were mainly associated with p53, TGF-β, and senescence signaling. Candidate core senescence-related genes were subsequently validated by RIP-Q-PCR. PS-NPs increased both the expression and METTL1 binding of CAT, CCT2, IMP3 , and IMP4 transcripts, effects that were reversed by NPT. Together, these results uncover an epitranscriptomic dimension of PS‑NPs toxicity and support NPT as a promising candidate for mitigating senescence‑associated disorders.