Climate change and health: understanding mechanisms will inform mitigation and prevention strategies

The cellular and molecular mechanisms of health impacts of climate change must be better understood to plan interventions that mitigate harm.

Climate-related disasters, including heatwaves, tropical cyclones, floods, droughts, and wildfires, have increased dramatically in the last few decades.¹ Cumulative exposure to climate-related stressors creates a compounding impact over time on human health and well-being, particularly where there are limited resources and limited adaptive capacity. This impact is greater in susceptible and vulnerable groups, including older people and those marginalized or minoritized. Understanding the drivers of climate-related health stress is essential for safeguarding human health via appropriate resilience and recovery strategies and interventions.

Climate-related stressors are a complex set of exposures and include thermal stress from heatwaves, nutritional deficiencies from drought or floods, pollution from wildfires, vector-borne illnesses from tropical cyclones, and heightened mental stress from increased adversity. Each of these components impacts the body in unique but overlapping ways, and the systemic damage from their combined effects can induce immediate and prolonged inflammation, oxidative stress, and disruptions in energy metabolism (including mitochondrial dysfunction) and alterations in epigenetic regulation; all of which can contribute to heightened morbidity and mortality over short- and long-term periods. Poor mental health is likely both a consequence of climate change stressors and a cause of further biological stressors.

Cellular and molecular biomarkers can aid in the early detection of which people who are more susceptible and vulnerable to climate-related stress and enable the targeted application of early therapeutic interventions. In addition, investigations into the cellular and molecular responses to therapeutics can detect biological vulnerability.

Available knowledge is derived from direct and indirect evidence (such as air pollution acting as a surrogate for air pollution from wildfires) and experimental models.

Acute and long-term inflammation

Inflammation plays a critical role in the body’s response to tissue damage and injury caused by climate-related stressors. When tissue is damaged, whether due to trauma, infection, or other causes, the inflammatory response is initiated. Immediate response to injury, release of inflammatory mediators, immune cell activation, vasodilation, and increased permeability are common inflammatory pathways activated in response to climate change-related tissue damage. Other inflammatory mechanisms, such as phagocytosis and removal of debris, fibroblast activation, tissue repair, and regeneration, as well as scar formation, are also present. Although few studies are available on the effects of hurricanes and floods on inflammatory makers, Cheng et al. assessed the lagged effects of heatwaves on clinical and subclinical cardiovascular indicators and reported increases of 0.20 % to 2.66 % in systemic inflammation markers (neutrophils: 2.52 % and neutrophil proportion: 2.66 %).²

By exploring volunteers exposed to wood smoke particles, Ghio et al. reported blood samples with an increased percentage of neutrophils; bronchial and bronchoalveolar lavage revealed a neutrophilic influx.³ The absolute neutrophil count in the blood increased by 23% after wood smoke particle exposure, while at follow-up, the absolute count increased significantly by 17%.³ Local and systemic inflammation likely play a role in the acute, subacute, and chronic effects of climate change-related health outcomes.

Oxidative stress

Oxidative stress is the imbalance between the production of reactive oxygen species (ROS) and the ability to counteract or detoxify their harmful effects, including the release of highly reactive free radicals that can damage cells and tissues. Few studies have to date evaluated oxidative stress in humans after climate change-related tissue damage, but studies in ectotherms (such as lizards)⁴ and mice⁵ have shown that oxidative stress may mediate the damage induced by heatwaves.

Wildfires and associated smoke are a growing source of air pollution, which can result in free radical release as part of the oxidative stress response.⁶ Choi et al. evaluated particulate matter ≤2.5μm (PM_2.5, a known toxicant from wildfires)-induced oxidative stress in rat lung epithelial cells, finding increased malondialdehyde and catalase mRNA by PM_2.5. A randomized controlled trial by Fang et al. in young participants to observe the effects of heat exposure found that pantothenic acid, a critical metabolite that protects cells against oxidative stress, and pyroglutamic acid, a compound that accumulates during oxidative stress, were significantly modified after the heat-exposure intervention.⁷ Oxidative processes are likely to contribute to both the immediate, intermediate, and long-term impacts on health associated with climate change-related damage.

Abnormal energy metabolism

After the injury created by a climate change-related disaster or other types of tissue damage, the body must undergo a series of metabolic changes to support the healing process. These changes are aimed at providing the necessary energy and nutrients for tissue repair, immune function, and overall recovery.

Metabolic processes, including glucose utilization, hormonal response to facilitate gluconeogenesis, and protein and fat metabolism, are activated to respond to climate change-related tissue damage. In prospective evaluations of people before and after Hurricane Katrina in the United States, Kamps et al. reported a significant decrease in the percent of blood glucose values between 71 and 299 mg/dL, the Children’s Hypoglycemia Index (CHI) total score and the CHI Situation subscale score, and an increase in the percent of blood glucose values ≥300 mg/dL.⁸ Climate change-related tissue damage may be present and contribute in the short-term, intermediate, and long-term, with consequences on health.

Mitochondrial dysfunction

Mitochondria are important for heat production and thermal regulation, playing a critical role in climate adaptation and extreme heat. Few studies exist about the impact of climate change-related disasters on mitochondria function; however, climate change-related disasters, such as heatwaves, may affect mitochondrial function by increased replication induced by increased energy demands,⁹ as well as by oxidative stress.¹⁰

An increased mitochondrial fission rate may lead to mtDNA mutation profiles during DNA replication. Systemic oxidative stress and chronic inflammation, both associated with climate change-related disasters,¹⁰ are two major pathways to tissue damage and have been shown to induce mtDNA somatic mutations and accelerate age-related mutation rates, leading to declining mitochondrial function.¹¹ Mitochondria with reduced functionality further increase oxidative damage, leading to greater systemic oxidative stress, systemic inflammation, and injury in specific organs.

Epigenetic changes

The epigenome is impacted by the environment, leading to phenotypic changes in cells and tissues. An epigenetic memory of past and recent climate could help humans to adapt over time to climate changes. For instance, epigenetics regulate heat shock proteins and unfolded protein response-related gene expression under heat stress; however, persistent epigenetic changes following heat stress may lead to maladaptive responses in the future.¹²

Cardenas et al. summarized the epigenetic changes in allergic and airway diseases associated with climate change-related disasters, highlighting differential DNA methylation of multiple genes and pathways, some of which were previously associated with asthma or allergy.¹³ Air pollution derived from wildfires may also impact DNA methylation. Studies from Xu et al. have reported 26 CpGs and 33 differentially methylated regions associated with wildfire-related particulate matter; these changes map to several genes related to inflammatory regulation and platelet activation.¹⁴

Health interventions

More funding is needed for research on early cellular and molecular biomarkers in response to climate change. The molecular and cellular mechanisms behind climate change-related health outcomes must be better understood in order to inform disaster responses; this will require infrastructure to collect samples, analyze data, and evaluate treatments. Improved risk prediction assessment tools based on molecular biomarkers could inform targeted interventions for long-term health treatments, in particular for at-risk individuals after climate change-related disasters. Special attention should be given those with higher biological susceptibility and vulnerability, including pregnant women, older people, children, as well as minoritized and marginalized communities.

Protecting the vulnerable

The impacts of climate change-related stressors are unequally distributed, as is access to resources and opportunities.¹ Discrimination, structural racism, redlining, and socioeconomic challenges combine with stressful life events in historically marginalized racial groups; these can contribute to chronic stress and aging-related processes. Susceptible individuals face heightened risks and challenges due to evolving climate change-related disasters. Older adults are particularly susceptible, as they may struggle to biologically adapt or behaviorally adapt to climate change-related disasters. Children, especially those living in poverty, are at risk due to their dependence on adults for support and limited capacity to adapt to climate change-related threats.¹⁵ Indigenous communities, whose livelihoods often rely on natural resources and ecosystems, face dislocation and cultural disruption as their traditional lands are impacted by climate change. Low-income individuals and communities are also vulnerable, as they may lack the resources and infrastructure to cope with the repercussions of climate change, with inadequate housing, limited access to healthcare, and reduced economic opportunities. There is an urgent need to include underrepresented groups in biomarker studies of climate change-related stressors and health outcomes to inform resilience strategies.

A biomarker approach to disaster preparedness and adaptation strategies will detect the people who are more vulnerable and help mitigate the impact of climate change on human health.

Figure 1. Cellular and molecular mechanisms of damage in climate-related health outcomes.

Environmental stresses cause local and systemic damage via molecular and cellular mechanisms.