In the environment, nanoplastic particles, such as nanopolystyrene, potentially cause toxicity on organisms at various aspects. We here employed endpoints of lifespan and aging-related phenotypes to further investigate the possible long-term effects of nanopolystyrene (100 nm) in Caenorhabditis elegans. After exposure from L1-larvae to adult day-3, nanopolystyrene at high concentrations (100 and 1000 μg/L) reduced the lifespan. Although nanopolystyrene (1 or 10 μg/L) did not affect the lifespan, nanopolystyrene (1 or 10 μg/L) could induce the more severe intestinal reactive oxygen species (ROS) production and decrease in locomotion behavior during the aging process compared with control. Moreover, nanopolystyrene exposure could cause the severe decrease in expressions of some immune response genes, hsp-6 gene, and genes encoding manganese-superoxide dismutases (Mn-SODs) during aging process, suggesting the severe suppression in innate immune response, inhibition in antioxidation defense system, and suppression in mitochondrial unfolded protein response (mt UPR) by nanopolystyrene. Our results highlight the potential of long-term nanopolystyrene exposure in reducing longevity and in affecting health state during the aging process in environmental organisms.