Chronic early-life exposure to diisopentyl phthalate, a plasticizer induced aging and impaired innate immunity via insulin-like and p38 MAPK pathways in Caenorhabditis elegans.

Plasticizers are widely used industrial chemicals, in addition, their extensive application has raised growing concerns about potential exposure-related health risks. Diisopentyl phthalate (DiPP), commonly used in the production of plastics and coatings, remains poorly characterized with respect to its toxicological effects. In this study, Caenorhabditis elegans was employed as the research model to evaluate the impact of early long-time exposure to DiPP on aging and innate immunity. The results demonstrated that DiPP exposure significantly shortened lifespan and induced the accumulation of lipofuscin and a reduced pharyngeal pumping rate, suggesting an accelerated aging phenotype. Molecular analysis revealed that DiPP upregulated the expression of daf-2 and age-1, while downregulating daf-16 and key components of the p38 MAPK signaling pathway. Additionally, DiPP exposure reduced nematode survival following Pseudomonas aeruginosa PA14 infection, indicating a decline in innate immunity. RT-qPCR and mutant validation experiments confirmed that both the insulin-like and p38 MAPK signaling pathways are implicated in DiPP-induced phenotypes consistent with accelerated immunological aging (defined here as an age-related decline in innate immune defenses, as measured by reduced pathogen resistance and decreased antimicrobial peptide gene expression). Collectively, these findings provide novel insights into the toxicological profile of DiPP and highlight its potential role in accelerating aging and impairing innate immunity.