Photoaged Polystyrene Microplastics Accelerate Aging in <i>Caenorhabditis elegans</i> via Ferroptosis-Linked Insulin Signaling Pathway

Microplastics (MPs) are known to induce diverse toxic effects across biological systems; however, how environmentally photoaged MPs influence organismal aging and the underlying mechanisms remain poorly understood. Here, virgin polystyrene (PS-0) and 45-day photoaged polystyrene (PS-45) were evaluated at environmentally relevant concentrations (0-100 μg/L) to assess aging-related effects and molecular pathways in <i>Caenorhabditis elegans</i>. Photoaging markedly altered PS physicochemical properties, including surface morphology, crystallinity, and functional groups. Exposure to 100 μg/L PS-0 or PS-45 significantly shortened lifespan, impaired physiological behaviors, and increased lipofuscin accumulation, whereas PS-45 at 10-100 μg/L elicited substantially stronger pro-aging effects. These enhanced toxicities were driven by particle-associated processes, particularly elevated environmentally persistent free radical generation and increased particle accumulation in nematodes. Mechanistically, PS-45 inhibited DAF-16 nuclear translocation and dysregulated insulin/IGF-1 signaling genes (<i>daf-2, age-1, pdk-1, akt-1</i>, and <i>daf-16</i>). Concurrently, PS-45 induced ferroptosis, as evidenced by increased Fe²⁺ and malondialdehyde levels, glutathione depletion, and suppression of <i>ftn-1</i>; these effects were alleviated by the ferroptosis inhibitor ferrostatin-1. Mutations in <i>daf-2, age-1, pdk-1, akt-1, daf-16</i>, and <i>ftn-1</i> significantly altered PS-45-induced aging phenotypes and ferroptotic stress, identifying the DAF-2-AGE-1-PDK-1-AKT-DAF-16-FTN-1 axis as a central regulatory pathway. Collectively, this study reveals a mechanistic link between insulin signaling and ferroptosis in MPs-induced aging and highlights the elevated environmental health risks posed by photoaged MPs.