Micro- and Nanoplastics Exposure Across the Lifespan: One Health Implications for Aging and Longevity

Microplastics (MPs) have most frequently been described as solid plastic particles between 5 mm and 1 µm in size [58]. This size-based convention is now widely adopted across environmental monitoring and toxicology, although refinements increasingly emphasize that MPs are synthetic or heavily modified polymers that are persistent, insoluble, and particulate [1]. By contrast, nanoplastics (NPs) lack a single agreed definition. A commonly used working definition includes particles in the range of 1 nm to 1 μm in size that display colloidal properties like Brownian motion, high specific surface area, and high affinity to natural colloids [59,60,61].

Importantly with respect to aging biology, this operational differentiation has functional significance because with smaller size in the sub-micrometer range, there is an increased probability of translocation, cell internalization, and subcellular interactions, and thus a shift in fundamental questions from irritation and barrier function effects linked with MPs, towards immune recognition, mitochondria disruption, and relevance/retention effects with NPs [62,63,64].

MNPs are also frequently categorized by origin as primary or secondary. Primary particles are intentionally manufactured at micro- or nanoscale and deliberately added to personal care products, industrial abrasives, specialized applications, and pre-production pellets/powders [65,66,67,68]. Secondary particles result from the successive erosion of larger plastic debris, comprising packaging, textiles, tires, paints, and marine debris, facilitated by mechanical abrasion, UV radiation, thermal cycling, and biological activity [69,70,71].

For health-relevant risk interpretation, secondary particles are particularly important because they typically dominate environmental burdens and exhibit highly heterogeneous morphologies (irregular fragments, films, fibres) and complex “exposure histories” that include prolonged weathering, additive leaching, sorption of co-pollutants, and biofilm colonization [72,73,74].

Due to the fact that secondary MNPs accumulate complex exposure histories (weathering, additive loss, pollutant sorption, and biofilm growth), their surface properties and reactivity can differ markedly from pristine materials; accordingly, environmentally aged particles are typically considered more exposure-relevant test materials than pristine, uniform spherical beads frequently used in experimental studies [75].

MNPs are consistently detected in the atmosphere, seawater, rivers, lakes, estuaries, sediments, and aquatic organisms across all continents, confirming global distribution and persistence [105,107,108]. Rivers, stormwater, and runoff act as major hydrological arteries that transport MNPs from inland and urban environments toward coastal and marine ecosystems, where they accumulate in sediments and biota [106,122]. Several continental-scale syntheses indicate that concentrations in inland waters and stormwater often exceed those reported in downstream estuaries, highlighting strong terrestrial to aquatic gradients and continuous inputs from land-based sources [106,122].

Terrestrial systems function both as long-term reservoirs and as active contributors to onward dispersion. Inputs arise from sewage sludge application, manure, tire wear particles, degraded plastic mulches, and atmospheric deposition, with particles persisting in soils, altering soil structure, and interacting with organisms in soil [122,123,124].

Airborne transport is now recognized as a central component of MNP dispersal, and a major source of xenobiotic exposure via inhalation in humans. MNPs have been detected in urban, suburban, rural, and remote regions, including mountainous and remote environments, confirming long-range atmospheric movement and deposition to land and water systems [105,106,125,126]. Indoor environments are repeatedly highlighted as significant exposure environments for humans because textile fibres and household plastics contribute substantially to indoor air and dust, which is particularly important for vulnerable populations spending prolonged time indoors [123,125,126].

Collectively, converging evidence indicates that MNPs form a pervasive environmental reservoir that links air, soil, freshwater, and marine compartments into a single interconnected exposure continuum [105,106,107,108,125].

Overall, MNPs enter aquatic food webs through the bioaccumulation documented from plankton to fish, seabirds, and marine mammals. Evidence indicates trophic transfer and retention within biological tissues, supporting concerns regarding long-term accumulation and biological impacts across species [107,123,124,127]. Parallel findings in terrestrial species demonstrate ingestion in livestock and wildlife, with species-specific vulnerability and physiological consequences [36,128,129].

Specifically, within aquatic ecosystems, fish and seafood occupy a pivotal position in the transfer of MNPs from the environment to higher trophic levels, including humans. MNPs have been widely documented in commercially relevant finfish, bivalves, crustaceans, and processed seafood products across diverse geographic regions [127,130,131,132,133]. Particle burdens vary substantially with feeding strategy and trophic position. Filter feeders such as mussels and oysters, as well as shrimp and small fish consumed whole, typically exhibit the highest levels of ingestion because gastrointestinal contents are retained in the edible fraction [130,131,132,133]. In contrast, for most larger finfish where viscera are removed prior to consumption, MNP levels in muscle tissue are generally lower, although contamination can still arise from post-harvest processing and packaging [131,132,134].

Risk evaluations by EFSA and subsequent reviews suggest that, under conservative assumptions, MNPs in seafood currently contribute a relatively minor proportion to overall exposure to plastic-associated additives and contaminants [133,135,136]. However, these assessments are limited by sparse data on particles smaller than 150 μm and on NPs, which may exhibit higher bioavailability. Moreover, MNPs present in seafood can act as vectors for co-occurring contaminants, including plastic additives, metals, hydrophobic organic chemicals, and microorganisms, raising concern for combined toxicological effects along aquatic food webs [37,127,130,131,132,137]. From a One Health perspective, contamination of marine food webs therefore represents a shared challenge linking environmental pollution, fish health, food safety, and human exposure.

Human exposure occurs primarily through ingestion and inhalation. Drinking water, seafood, salt, fruits, vegetables, and processed foods have been shown to contain MNPs, with estimated annual intakes in the tens of thousands of particles per person, although significant methodological uncertainty remains [123,124,138]. Importantly, detection of MNPs in human faeces, placenta, blood, lung and brain tissue, and other biological matrices confirms internal exposure and indicates the potential for bioaccumulation across the lifespan [107,124,139,140,141,142].

Within a One Health perspective, terrestrial domestic animals and companion animals are increasingly viewed as environmental sentinels because they share indoor air exposure, interact with contaminated soils and food chains, and may reflect exposure burdens relevant to human health (Figure 2). Their role in manure to soil to crop pathways is particularly important for agricultural exposure cycles and food security [124,134,141].

Ingestion and inhalation currently represent the most established exposure pathways in humans [141,143]. Pharmacokinetic analyses indicate that gastrointestinal absorption is generally low, yet not negligible. Multiple mechanisms permit barrier passage, including transcytosis in enterocytes, uptake by M-cells, persorption through epithelial discontinuities, and phagocytosis by immune cells, with efficiency strongly dependent on particle size, surface charge, and chemistry [141,144,145]. Advanced intestinal co-culture models support the capacity of NPs to cross via passive diffusion and endocytic routes, reinforcing biological plausibility for systemic entry [146].

The respiratory tract represents an additional relevant entry point, with inhalation being the main exposure route to these xenobiotics. Only particles below approximately 5 µm efficiently reach the lower lung, although the presence of larger particles in lung tissue suggests possible vascular entrapment after systemic redistribution rather than direct deposition [141]. Human studies reporting MNPs in lung tissue, sputum, blood, placenta, and brain confirm that barrier translocation occurs in real-world contexts [147,148,149,150]. Collectively, the available evidence supports the conclusion that while the majority of ingested or inhaled MNPs may be cleared through mucociliary or gastrointestinal mechanisms, a consistent fraction of particles can penetrate biological barriers and enter systemic circulation, particularly when they fall within the micro-to-nano size range [141,147,151].

Experimental work in rodents demonstrates that absorbed particles do not remain confined to the entry site but distribute to multiple organs including the liver, kidney, gut, spleen, brain, and reproductive tissues, with smaller particles exhibiting broader distribution and higher tissue retention (Figure 3) [144,152,153]. Physiologically based toxicokinetic models in mice indicate that gastrointestinal absorption and faecal elimination dominate whole-body kinetics, while organ accumulation reflects size-dependent differences in binding and clearance, including reduced urinary elimination for smaller particles [23]. Model estimates indicate that nanoplastics and microplastics (1 to 10 μm) accumulate progressively in human tissues across the lifespan, reaching substantially higher levels in adults than in children. Specifically, cumulative intake is estimated at 8.32 × 10³ particles per capita (90% CI, 7.08 × 10² to 1.91 × 10⁶) or 6.4 ng per capita (90% CI, 0.1 to 2.31 × 10³) by 18 years of age, whereas accumulation increases to 5.01 × 10⁴ particles per capita (90% CI, 5.25 × 10³ to 9.33 × 10⁶) or 40.7 ng per capita (90% CI, 0.8 to 9.85 × 10³) by 70 years of age, indicating a substantial age-dependent increase in retained particles in body tissues [154].

Human-directed toxicokinetic assessments propose that most ingested particles are excreted, but a systemically absorbed fraction can accumulate in hepatosplenic organs and potentially the brain, with clearance likely involving macrophage-mediated processes and reticuloendothelial sequestration [141,147,151]. Importantly, existing evidence suggests the possibility of incomplete clearance and long residence times. At the cellular scale, MNPs can be internalized via endocytosis and persist over cell divisions, providing a mechanistic basis for cellular bioaccumulation and potentially chronic intracellular exposure [148,149].

Current knowledge strongly indicates size-dependent fate characteristics. NPs show the greatest capacity for barrier crossing and widespread tissue access, including convincing evidence of central nervous system entry in animal models [144,151,153]. Smaller MNPs demonstrate systemic translocation with accumulation in major metabolic and immune organs and are often associated with more tissue-level alterations [23,153]. Larger MPs are more likely confined to the gastrointestinal tract or become physically trapped within vascular structures, resulting in far more limited systemic distribution [141,143].

The relevance of these processes for aging relies on two intertwined considerations. First, MNPs engage biological pathways linked to the hallmarks of aging [147,156,157]. Second, aging itself alters barrier integrity, immune clearance mechanisms, and physiological resilience. Age-associated increases in gut and lung permeability, reduced macrophage efficiency, and altered inflammatory tone could theoretically enhance absorption, systemic persistence, and downstream tissue vulnerability [144,147,158]. However, these implications remain largely inferential, and more research is required. There is a paucity of direct, age-stratified toxicokinetic data, and lifetime accumulation dynamics remain unclear.

Across a wide range of models, exposure to MNPs has been shown to induce oxidative stress [163,164]. Studies demonstrate increased production of reactive oxygen species (ROS), depletion of antioxidant systems including glutathione, superoxide dismutase, and catalase, and accumulation of lipid peroxidation, protein oxidation, and DNA damage [156,159,161,162]. NPs are particularly potent, as they can enter mitochondria, impair electron transport chain function, cause membrane depolarization, and promote sustained oxidative stress [159,160,165]. Particle size, surface chemistry, and environmental aging modify these effects, with smaller, positively charged, and UV-aged particles presenting higher redox reactivity [153,161,162].

Aging organisms already exist in a state of weakened antioxidant capacity and heightened oxidative load; therefore this interaction provides strong mechanistic plausibility that chronic low-level exposure could intensify age-related redox imbalance, although robust long-term dose–response data in humans remain unavailable [46,156,159,165].

MNPs consistently activate innate immune signalling. Experimental work shows activation of NFκB, MAPK, and NLRP3 inflammasome pathways, with associated increases in cytokines such as TNFα, IL1β, IL6, and IL8 across gut, lung, liver, and immune cell systems [156,159,166,167,168,169,170,171,172,173]. Macrophages and dendritic cells internalize particles and show ROS-dependent activation with phenotype shifts [170,172,174,175,176].

This chronic, low-grade immune activation parallels the biology of inflammaging, suggesting that persistent tissue retention of particles could theoretically reinforce inflammatory tone and contribute to immune dysregulation over time. To date, however, direct evidence linking these immune effects to human aging trajectories remains limited and largely inferential [26,156,165,177,178].

Multiple studies indicate that NPs, and in some contexts, small MPs, reach mitochondria where they disrupt structure and function. Reported effects include cristae damage, mitochondrial membrane depolarization, ATP reduction, respiratory chain impairment, calcium imbalance, and excessive mitophagy [147,159,160,165,167,179]. Functional consequences include apoptosis, metabolic disturbance, insulin resistance in muscle systems, and neurodegeneration-like phenotypes in neuronal models [88,159,165,167,179].

Since mitochondrial decline is a central contributor to frailty, neurodegeneration, and metabolic disease in aging, these findings support a biologically plausible pathway through which environmental plastic exposure may exacerbate age-associated mitochondrial vulnerability [88,156,159,160,165].

Experimental and review evidence indicates that MNPs can promote cellular senescence. Reported mechanisms include oxidative DNA injury, mitochondrial dysfunction, impaired autophagy, activation of DNA damage responses, and p53-related signalling, together with secretion of cytokines consistent with senescence-associated secretory phenotype profiles [156,161,167]. Size-dependent and dosage-dependent mechanisms have been proposed, including ferroptosis and p53–Fosl1–Slc7a11 signalling for NPs, whereas MPs may drive metabolic reprogramming and inflammatory signalling involving YAP pathways [167].

Senescent cell accumulation contributes to tissue dysfunction and systemic inflammaging. Consequently, MNP-induced senescence represents a plausible contributor to accelerated biological aging. However, organism-level confirmation, particularly under environmentally relevant exposure scenarios, remains sparse and represents a major gap in the literature [156,161].

Overall, mechanistic evidence indicates that MNPs may activate biological pathways central to aging, including oxidative stress, inflammation, mitochondrial injury, and senescence signalling. This convergence supports biological plausibility that lifelong exposure could interact with aging biology and potentially influence healthspan. However, most studies rely on short-term and relatively high-dose exposures. Determining the relevance of chronic, low-dose environmental exposure for aging outcomes will require aging-focused experimental systems, longitudinal human studies, and integration within life-course exposomics frameworks.

MNP contamination affects all major environmental compartments. From a One Health and aging perspective, the critical observation is the common biological responses to MNP exposure across taxa. Laboratory and field studies in aquatic and terrestrial organisms consistently report oxidative stress, immune dysregulation, altered lipid and energy metabolism, mitochondrial dysfunction, and impaired reproduction following chronic exposure [25,194,195]. These pathways overlap substantially with hallmarks of aging, including mitochondrial dysfunction, loss of proteostasis, altered intercellular communication, and stem cell exhaustion [91].

Quantitatively, experimental studies in fish, mollusks, and rodents often report increased reactive oxygen species levels ranging from 20 to 200 percent above controls, accompanied by significant reductions in antioxidant enzyme activity and ATP production, depending on particle size and exposure duration [25,156]. While these exposure levels exceed current environmental estimates, the directionality and consistency of responses support the notion that MNPs activate conserved stress pathways rather than species-specific toxic effects.

From a surveillance standpoint, wildlife and domestic animals exposed to chronic environmental contamination can therefore function as sentinels showing the effects of cumulative biological stress due to MNPs. Observations of reduced reproductive fitness, impaired immune competence, and altered metabolic profiles in animal populations may provide early warnings of processes that, under prolonged exposure and in the context of declining resilience, could influence human aging trajectories.

Aging may fundamentally modify susceptibility to exposure and subsequent internalisation to MNPs. Age-related changes in epithelial barrier integrity, including increased intestinal permeability and reduced mucociliary clearance, may enhance internalization of inhaled or ingested particles [20,196]. Experimental and clinical studies indicate that intestinal permeability can increase in older adults, while immune surveillance and phagocytic capacity decline progressively with age, potentially impairing clearance of persistent particles.

Immunosenescence may further promote persistence of internalized MNPs and sustain low-grade inflammatory signalling [196]. These processes occur against a background of multimorbidity and polypharmacy, although it is still no clear understanding of how this may affect MNP absorption rates. Furthermore, older adults recovering from disease through rehabilitation already face limited physiological reserve, and chronic exposure to MNPs may further hinder successful rehabilitation and healthspan maintenance by sustaining inflammatory and metabolic stress, underscoring the need to explicitly consider these populations in MNP research.

Importantly, aging populations experience cumulative exposure to multiple environmental stressors. Fine particulate matter (PM2.5), for example, has been associated with increased mortality and accelerated biological aging, with long-term exposure above 10 µg/m³ linked to measurable reductions in life expectancy [197]. Many of the molecular pathways activated by PM2.5 overlap with those reported for MNPs, including oxidative stress, inflammation, and mitochondrial dysfunction. Within this broader exposomic context, MNPs should be viewed as incremental contributors to physiological burden rather than dominant drivers of pathology.

At the population level, the potential relevance of MNPs for aging emphasizes the importance of preventive environmental health strategies. Although current evidence does not support age-specific exposure thresholds or clinical guidelines, the mechanistic convergence between MNP-induced effects and hallmarks of aging supports their inclusion within healthy aging and longevity research agendas [91].

Primary prevention strategies include reduction of plastic production, more effective recycling, and addressing of environmental pollution. These measures align protection of human health with preservation of ecosystem services and biodiversity. Secondary prevention approaches may involve integration of MNP exposure metrics into exposomic and geroscience cohorts, enabling longitudinal evaluation of associations with biomarkers of biological aging, including epigenetic clocks, chronic inflammation profiles, mitochondrial function, and functional decline [198].

Taken together, these considerations position MNPs as components of a shared ecological and biological context that may modulate aging trajectories across species. A One Health approach therefore provides a scientifically coherent framework for addressing environmental sustainability, animal health, and human healthy aging in an increasingly plastic-dependent world.

Limitations in MNP research arise not only from analytical constraints but also from experimental design. Conflicting results frequently reflect uncontrolled variation in particle type, size, aging, dose, and exposure matrix, which are rarely standardized across studies [199,200,201]. A major bias is the extensive use of monodisperse spherical polystyrene as a model plastic, despite its poor representativeness of heterogeneous environmental polymers, limiting extrapolation to real exposure scenarios [202,203].

Many studies also rely on supra-environmental concentrations, short exposures, and simplified endpoints such as cytotoxicity or oxidative stress, which can overestimate hazard and reduce comparability [201,204,205]. Inconsistent quality control and reporting of particle characterization and experimental conditions further limits reproducibility and risk assessment [8,206]. Together, these issues hinder generalization of findings from idealized nanoplastics to complex environmental mixtures.

Detection and quantification of NPs in environmental and biological samples remains one of the most significant barriers. Spectroscopic approaches such as micro-FTIR and Raman spectroscopy progressively lose discriminatory capability below 1 µm, while thermal analytical platforms including pyrolysis-GC/MS and TED-GC/MS provide polymer mass but do not resolve particle number, morphology, or surface chemistry, especially in complex matrices such as blood or tissues [207,208,209,210,211,212,213]. Reported detections often vary widely across studies, and there is credible concern regarding contamination and false positives, particularly when detection limits may approach or exceed expected environmental exposure levels [143,212,213]. Many studies still lack harmonized quality assurance protocols, including blanks, recovery efficiencies, and standardized reporting units, which limits cross-study comparison and risk assessment frameworks [207,211,212,213]. Ongoing work is exploring enhanced Raman detection, SERS, advanced imaging mass spectrometry, and tracer-labelled plastics to improve traceability across the lifespan [77,207,213]. Parallel development of standardized internal body burden metrics in blood, brain, and other organs is essential to characterize lifetime accumulation and exposure variability [139,140,212,214,215].

Most toxicological knowledge is derived from experiments using young animals, short exposures, or simplified polystyrene spheres at concentrations that often exceed realistic human levels [25,37,144,204]. Experimental work rarely incorporates aging physiology, despite clear mechanistic overlaps between MNP toxicity and processes such as inflammaging, mitochondrial decline, and cellular senescence [144,156,204]. There is a strong need for aged animal models, disease-susceptible organisms, senescent cell systems, and aged human organoid platforms. Lifespan-oriented study designs spanning prenatal development to late life, combined exposures with sorbed pollutants or microbial biofilms, and environmentally realistic particle sizes and concentrations, and polymer compositions will be essential for relevance to human aging biology [156,204,216].

Human evidence remains limited to small or cross-sectional biomonitoring studies and lacks long-term epidemiological designs capable of assessing frailty, multimorbidity, cognitive decline, or mortality outcomes across decades [139,143,212,214]. Older adults undergoing rehabilitation often present with reduced physiological reserve and multiple comorbidities, underscoring the need for MNP research to explicitly consider aging populations whose compromised resilience may amplify the functional consequences of chronic environmental exposures. There are few integrative One Health studies tracing particles from environmental reservoirs into food webs and ultimately to human internal dose and biological effect [25,217]. Brain accumulation and potential links to neurodegenerative processes and dementia have emerged as an important research frontier following the recent detection of MPs in human brain tissue, but mechanistic and epidemiological understanding remains limited [139,218]. Integration of exposomics, multi-omics biomarkers of aging, exposure–response modelling, and advanced analytics represents a widely recognized path forward to move beyond association toward causal inference [25,156,198,217].

Critical next steps include: (1) development and harmonization of high-resolution NP detection with rigorous quality assurance and control; (2) implementation of aging-relevant, disease-sensitive in vitro and in vivo models at environmentally realistic doses; and (3) integration of exposomics and multi-omics platforms to elucidate mechanistic pathways linking MNP exposure to aging and chronic disease [139,156,198,204,217,219]. Additionally, future studies should also incorporate detailed kinetic analyses of adsorption–desorption processes of other pollutants, such as heavy metals, carried by MNPs and intracellular pollutant release, including time-resolved investigations of how particle aging or photo-oxidation alters cargo dynamics and toxicity under realistic exposure conditions [3,43,218,220].