MP exposure generates excessive reactive oxygen species (ROS), surpassing the cellular antioxidant defense system, thereby creating a state of oxidative stress [3]. This redox imbalance disrupts mitochondrial function, triggering a vicious cycle of ROS overproduction, mitochondrial DNA (mtDNA) damage, and compromised bioenergetic efficiency [4]. Mitochondria, as central regulators of cellular metabolism, become primary sites of damage, contributing to inflammatory responses and metabolic dysregulation [5]. This short communication examines the mechanistic pathways linking MP-induced oxidative stress, mitochondrial dysfunction, and NEG, providing an integrative perspective on their role in disease progression.

MICROPLASTICS AND REDOX IMBALANCE: MOLECULAR BASIS

MPs induce oxidative stress through direct and indirect mechanisms. Direct effects include physicochemical interactions between MP particles and cellular membranes, leading to lipid peroxidation and protein carbonylation [6].

Indirectly, MPs act as carriers for heavy metals, persistent organic pollutants (POPs), and endocrine-disrupting chemicals (EDCs), all of which contribute to ROS generation and mitochondrial dysfunction [7]. The oxidative environment promotes glycoxidation, a process that accelerates AGE formation, further exacerbating metabolic dysfunction [8].

MP-associated AGEs interact with their receptors (RAGEs), initiating pro-inflammatory signaling cascades, activating nuclear factor kappa B (NF-κB), and upregulating cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) [9]. This chronic inflammatory state perpetuates cellular damage and accelerates age-related diseases, including insulin resistance and neurodegeneration [10].

MITOCHONDRIAL DYSFUNCTION AND AGE ACCUMULATION

Mitochondria play a dual role in MP-induced toxicity: they act as both a source and a target of oxidative stress. MP exposure disrupts mitochondrial membrane potential, leading to increased proton leakage, impaired ATP synthesis, and apoptosis [11]. The oxidative modifications of mitochondrial proteins and lipids contribute to defective mitophagy, further aggravating cellular stress [12]. Additionally, MP-induced mitochondrial dysfunction has been linked to impaired glucose metabolism and insulin signaling, reinforcing the association between MPs, NEG, and metabolic disorders [13].

IMPLICATIONS FOR AGING AND DISEASE PATHOGENESIS

The link between MP exposure and metabolic dysfunction highlights an urgent need for further research into its role in aging and chronic disease progression. Persistent MP exposure accelerates biological aging through oxidative stress-induced telomere attrition, DNA methylation alterations, and mitochondrial biogenesis impairment [14]. Additionally, the role of AGEs in neurodegenerative diseases, such as Alzheimer's and Parkinson's, underscores the relevance of MP-mediated glycation in neuronal aging [15]. Cardiovascular diseases, another significant aging-related pathology, are exacerbated by MP-induced endothelial dysfunction and inflammation, reinforcing their contribution to systemic metabolic imbalance [16].

FUTURE DIRECTIONS AND SCOPE

This short communication aims to consolidate existing evidence on the molecular mechanisms underlying MP-induced oxidative stress, mitochondrial dysfunction, and AGE accumulation. By integrating findings from environmental toxicology, molecular biology, and metabolic research, we seek to establish a comprehensive framework for understanding MP-associated disease risk. Future research should focus on:

1. Identifying biomarkers for MP-induced oxidative damage and glycation pathways [17].
2. Developing therapeutic strategies to mitigate MP-induced metabolic stress, including antioxidant supplementation and autophagy modulation [18].
3. Investigating potential interventions, such as dietary modifications and regulatory policies, to limit MP exposure and its systemic effects [19].

CONCLUSION

Microplastics are increasingly implicated in oxidative stress-mediated metabolic disruptions, highlighting their significant impact on human health. This short communication elucidates the molecular basis of MP-induced redox imbalance, mitochondrial dysfunction, and AGE accumulation, establishing a mechanistic link between environmental microplastic exposure and metabolic disease pathogenesis. The excessive ROS production associated with MPs disrupts mitochondrial integrity, exacerbates glycoxidation, and amplifies chronic inflammation, collectively accelerating aging-related diseases. Given the growing evidence of MPs’ systemic toxicity, future research should prioritize the identification of reliable biomarkers for MP-induced oxidative damage, the development of therapeutic strategies to mitigate metabolic stress, and policy-driven interventions to reduce human exposure. By addressing these critical knowledge gaps, this short communication contributes to a deeper understanding of MP toxicity and underscores the need for proactive public health measures to combat its biochemical and physiological consequences.

ACKNOWLEDGMENTS

The author would like to express sincere gratitude to Sri Aurobindo Medical College and PG Institute, SAIMS Hospitals, Sanwer Road, Indore, Madhya Pradesh, India, 45355, and Sri Aurobindo University (SAU), Indore, India. The support, facilities, and resources provided by both institutions were instrumental in the successful completion of this research.