The Role of the Exposome in Aging and Age-Related Diseases: A Comprehensive Review

ABSTRACT

Aging is a very complex process, which is genetically and environmentally driven. Aging and age-related disease onset are strongly dependent on the exposome (all environmental exposures from conception to death). This review focuses on how environmental load accumulated throughout life, possibly through oxidative stress, inflammation, and epigenetic modulation, influence aging. Specific environmental contributors to neurodegenerative diseases like Alzheimer’s and Parkinson’s and how they have biological impact are explored by us. We also review recent advances performed in exposome research focusing on biomonitoring and multiomics approaches, which allow for novel discovery of the mechanisms for aging related to exposome. We also suggest potential preventive actions that will help to offset the environmental risks and achieve healthy aging. Knowing how the environment plays a role in aging gives the opportunity to develop better strategies to prevent and manage diseases related to age.

INTRODUCTION

The exposome encompasses all the environmental factors that a person encounters in its lifetime affecting biological processes and the overall health of the individual.[1] The exposomes range from air- and water-polluting agents to diet and lifestyle choices and occupational hazards.[2] Such environmental components, if prolonged, may lead to accelerating cellular aging, the disruption of metabolism,[3] or an increase in chronic diseases including cardiovascular diseases,[4] diabetes,[5] or cancer.[6] Environmental toxins and lifestyle factors are also associated with the later development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.[7]

This review describes how the exposome influences aging with emphasis on mechanistic focus and offers potential strategies to counteract the adverse effects of the exposome on health. First, we provide a basic structure, concerning environmental exposure and its impact on aging. Next, we examine the role of oxidative stress, inflammation, and epigenetic modifications.[8] Then we discuss advancement in exposome research and how the exposome is related to neurodegenerative diseases. We eventually propose future directions and preventive strategies that will reduce the risk of exposomes and aging positively.

KEY ENVIRONMENTAL EXPOSURES AND THEIR IMPACT ON AGING

Environmental factors are important for the aging process and the development of age-related diseases. Cellular and systemic aging is caused by air pollution, pesticides, and heavy metals, in addition to bad dietary habits and lifestyle choices [Figure 1]. The following sections provide a discussion of the major environmental exposure and its effect on aging, based on scientific findings [Table 1].

Figure 1.

External factors (or environmental factors) and internal factors (or lifestyle factors) contributing as an exposome that influence the aging process

Table 1.

Summary of key environmental exposures and their effects on aging

Environmental Exposure	Effects on Aging	Ref.
Air Pollution	Accelerates cellular aging, promotes inflammation, increases the risk of cardiovascular and neurodegenerative diseases.	[9]
Heavy Metals (Lead, Arsenic, Mercury)	Causes mitochondrial dysfunction, oxidative damage, and neurodegeneration.	[10,11]
Pesticides and Endocrine Disruptors	Disrupts hormonal balance, contributes to neurodegeneration and immune dysfunction.	[12,13]
Diet and Nutritional Factors	High processed food intake leads to chronic inflammation, while antioxidants help mitigate aging.	[14]
Lifestyle Factors (Smoking, Alcohol, Inactivity)	Increases oxidative stress, induces epigenetic alterations, and exacerbates aging-related inflammation.	[2]

Air pollution

Fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone exposure over a long time led to the acceleration of cell senescence and induced systemic inflammation. It has been shown in studies that air pollution increases rates of cognitive decline and cardiovascular diseases. These risks can be greatly reduced under regulatory measures that will improve air quality.[9]

Heavy metals

Mitochondrial function, oxidative stress, and neurodegeneration are known to be affected by heavy metals such as lead, arsenic, and mercury. Research has shown that these metals interfere with essential cellular function and are also involved in metabolic and neurodegenerative disorders.[10,11]

Pesticides and endocrine disruptors

Organophosphates, a type of pesticide, can impede both neurodegeneration and immune system dysregulation.[12] Endocrine disruptors, like bisphenol A (BPA) and phthalates, slow down biological aging and diminish the disease availability. There should be limitations of such chemicals and regulatory policies to minimize these risks.[13]

Diet and nutritional exposures

Consumption of AGEs and highly processed foods as part of a diet has been linked to induced chronic inflammation and metabolic diseases.[14] However, a diet rich in antioxidants and essential nutrients can not only prevent this oxidative damage but also take care of age and thus the probability of a decline in age-related diseases.[15]

Lifestyle factors

An unhealthy lifestyle like alcohol and tobacco consumption causes oxidative stress and epigenetic changes. Physical inactivity exacerbates inflammation, accelerating aging-related decline.[16] Public health initiatives promoting smoking and raising physical activity may reduce the prevention and mitigation of these risks.[17]

EPIGENETICS, OXIDATIVE STRESS, AND INFLAMMATION IN AGING

Epigenetic modifications occurring as a consequence of environmental exposures have a major impact on gene expression and on aging and disease susceptibility.[18] There is an imbalance of free radicals and antioxidants, which may cause oxidative stress and deteriorate cellular components accelerating aging.[15] Cellular decline also relies on mitochondrial dysfunction,[19] whereas chronic inflammation is a key pathway for environmental exposures to cause age-related diseases.[20]

Research into these mechanisms offers the opportunity to find interventions that might mitigate the downside of the environmental factors on aging. By making healthy lifestyle choices, eating a healthy diet, and taking the appropriate medications, one can lower the problem of oxidative stress and inflammation, thereby possibly slowing down aging and improved overall wellbeing.[21]

EXPOSOME AND NEURODEGENERATIVE DISEASES

Environmental exposures are now associated with the progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Oxidative stress, inflammation, and epigenetic modifications are influenced by the exposome and thus brain aging.

Alzheimer’s disease

It has been studied that air pollution and heavy metal exposure multiply the risk of Alzheimer’s disease by facilitating the formation of amyloid-beta and tau pathologies. Disease progression is modulated by lifestyle factors, which implies the possibility of the most basic intervention strategies.[22]

Parkinson’s disease

There is a strong association of pesticides, such as paraquat and rotenone, with an increased risk of Parkinson’s disease due to the ability of these compounds to damage dopaminergic neurons. Additionally, neurotoxicity is furthered by industrial chemicals, such as solvents and heavy metals, that should be regulated in the context of environmental exposures.[23]

Other cognitive disorders

Multiple environmental exposures exert combined effects on the risk of cognitive impairment and dementia.[24] It is emerging evidence that environmental toxins lead to a dysbiosis of the gut microbiome, which drives neurodegeneration, offering a possible target of future interventions.[25]

FUTURE DIRECTIONS, RESEARCH GAPS, AND PREVENTIVE STRATEGIES

Understanding the exposome’s contribution to aging and disease only emphasizes the importance of preventative interventions against environmental risks to enhance public health.

Policy implications

Using better environmental policies on pollutants, heavy metals, and endocrine disrupters is crucial to reducing their exposures. Environmental aging factors will be addressed through government policies promoting cleaner air, safer food sources, and lower chemical contaminants.[26]

Personalized medicine

The development of exposome research helps assess individual risk from environmental toxins and explains genetic susceptibilities to them. An exposome profile could be used to best optimize or mitigate exposure-related risks and/or health outcomes that are personalized to an individual.[27]

Intervention strategies

Dietary and lifestyle habits that are healthier to adopt include reduction of processed food intake, increased physical activity, and minimizing exposure to recognized toxins, which can mitigate the negative effects of the exposome. Prominent public awareness campaigns and preventive personal healthcare will be required to improve long-term wellbeing and healthy aging.

Future research gaps

Despite considerable progress in exposome research, many gaps exist. The relation and the interaction between genetic predisposition and environmental exposures need to be further investigated.[28] The knowledge of how genetic variability intersects with exposomic factors might be used for the personalization of intervention strategies. Second, while environmental exposure has been shown to cause neurodegeneration, the relevant molecular mechanisms through which environmental exposure might promote disease progression are not known. However, further research is required to determine specific biomarkers that are predisposing to exposome-induced aging and disease.

Also, the putative role of the gut microbiome in the response of the exposome on aging has yet to be explored.[29] There is known to be an important role of the gut-brain axis in neurodegeneration, but little is known about how environmental factors impact health and microbial communities and thereby affect aging-related diseases.[30] Finally, effective long-term epidemiological studies in which groups of individuals are followed throughout their lives are required to fully understand the cumulative effects of exposure to exposomic factors.

CONCLUSION

Aging and age-dependent adversely influencing diseases such as Alzheimer’s and Parkinson’s are of considerably high degree influenced by the exposome. Cellular aging is influenced by the exposures to environmental pollutants, heavy metals, pesticides, diet, and lifestyle choices, leading to occurrence of oxidative stress, inflammation, and epigenetic changes. With advances in exposome research, mainly biomonitoring, AI-driven analysis, and multiple omics approaches, these interactions are understood and personalized risk assessments to this heterogeneous exposure are possible.

Future efforts that minimize environmental risks include going beyond regulatory policies and adoption of personal medicine and lifestyle intervention. The development of suitable strategies to overcome exposome-related aging risks will require strengthening of interdisciplinary collaboration of researchers, policymakers, and healthcare professionals. With the help of scientific progress, we can help prevent age-related diseases and increase longevity, better quality of life, and lessen the world’s burden of the diseases associated with aging.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.