Molecular and Cellular Effects of Microplastics and Nanoplastics: Focus on Inflammation and Senescence

Abstract

Microplastics and nanoplastics (MNPs) are ubiquitous environmental contaminants. Their prevalence, persistence, and increasing industrial production have led to questions about their long-term impact on human and animal health. This narrative review describes the effects of MNPs on oxidative stress, inflammation, and aging. Exposure to MNPs leads to increased production of reactive oxygen species (ROS) across multiple experimental models, including cell lines, organoids, and animal systems. ROS can cause damage to cellular macromolecules such as DNA, proteins, and lipids. Direct interaction between MNPs and immune cells or an indirect result of oxidative stress-mediated cellular damage may lead to increased production of pro-inflammatory cytokines throughout different MNP-exposure conditions. This inflammatory response is a common feature in the pathogenesis of neurodegenerative, cardiovascular, and other age-related diseases. MNPs also act as cell senescence inducers by promoting mitochondrial dysfunction, impairing autophagy, and activating DNA damage responses, exacerbating cellular aging altogether. Increased senescence of reproductive cells and transfer of MNPs/induced damages from parents to offspring in animals further corroborates the transgenerational health risks of the tiny particles. This review aims to provoke a deeper investigation into the notorious effects these pervasive particles may have on human well-being and longevity.

Keywords: DNA damage; cellular aging; cytotoxicity; environmental pollutants; human health; inflammation; microplastics; nanoplastics; reactive oxygen species; senescence.

Figure 1

Micro- and nanoplastic (MNP) weathering process, cellular uptake, and consequent oxidative stress in cells. Plastic particles undergo aging through UV radiation and photo- and thermal oxidation, leading to structural changes and chemical alterations on the surface of the particles. When transported into humans and animals, these microscopic particles are distributed across systems and ultimately taken up by various cell types. MNP internalization is accompanied by the generation of free radicals inside cells, meaning elevated reactive oxygen species (ROS) levels and ensuing oxidative stress. The presence of MNPs within cells and consequent ROS overload damage organelles and impair their functions. At molecular levels, lipid and protein oxidation debilitates their structure and function, while oxidative DNA damage may give rise to mutations.

Figure 2

Molecular and cellular events leading to inflammation and senescence upon MNP exposure. Orange cube: key molecular consequences; orange sphere: detailed expression of relevant biomarkers; green cube: key cellular consequences; green sphere: detailed expression of relevant biomarkers; solid lines indicate the interconnectedness of biomarkers and key events; double-sided arrow: evidence suggests that key events are linked; dashed lines suggest that the key event may, in part, be a consequence of another key event; asterisk (*): indicates that IL-6 expression is downregulated in certain contexts due to microplastic exposure.

Figure 3

MNP exposure elicits the molecular hallmarks of aging in human and animal cells. Mitochondrial dysfunction (in the forms of excessive ROS generation, loss of membrane potential, and mitochondrial DNA leakage) and ROS-mediated damages such as impaired autophagy, loss of proteostasis, DNA damage, and chromatin modifications trigger senescence in cells. Long-term senescence is detrimental to normal tissue function and ensues aging-related disease manifestations.