New research highlights the dominant role of environmental exposures in health outcomes, disease risk and longevity.
The relative influence of genetics on health outcomes has been the subject of debate for decades; now, new research published in Nature Medicine today points to the overwhelming role of the exposome – the sum of environmental exposures throughout life – in determining mortality risk. According to the study, the exposome accounts for nearly ten times more variation in mortality risk than genetic predisposition, prompting renewed interest in how external factors influence disease, aging and healthspan [1].
The concept of the exposome encompasses all external exposures, from air quality and social conditions to diet and chemical contaminants, which interact with internal biological factors to shape health trajectories. The emerging field of functional exposomics seeks to systematically track and analyze these interactions using high-throughput biomarkers, AI and real-world testbeds such as cities, clinics and communities. Researchers in organizations such as the Biomarkers of Aging Consortium and the European Human Exposome Network are now working to establish standardized methodologies to quantify the exposome’s impact on health, providing actionable insights for precision medicine and public health policies.
While genetics contribute to disease susceptibility, emerging evidence suggests that the exposome exerts a significantly greater influence on healthspan and mortality risk. The study in Nature Medicine found that exposome-related factors account for nearly ten times more variation in mortality risk than genetic predisposition alone. Furthermore, certain exposures – such as air pollution [2], socioeconomic status, and psychological stress – can amplify genetic vulnerabilities, making it essential to examine these interactions rather than viewing genetics and environment in isolation. This emerging understanding has strengthened calls for a Human Exposome Project to systematically measure and analyze these factors, mirroring the scale and ambition of the Human Genome Project.
Longevity.Technology: The implications of this research extend far beyond academia; they challenge prevailing assumptions in healthcare and public policy, which have long prioritized genetic research and pharmaceutical interventions over environmental and behavioral determinants of health. If the exposome is indeed the dominant factor in longevity and disease risk, healthcare strategies must pivot toward preventive measures, public health interventions and systemic changes that mitigate harmful exposures. Governments and policymakers may need to reconsider urban planning, pollution control, workplace regulations and food quality standards to create healthier environments. A shift of this magnitude would not only influence clinical practice but also reshape insurance models, economic policies and global health initiatives.
The upcoming Exposome Moonshot Forum, scheduled to take place in Washington DC from 12-15 May, aims to build momentum for a coordinated international effort to map environmental exposures and integrate them into healthcare policy. The initiative seeks to define the necessary resources, policies and collaborations to advance the Human Exposome Project, ensuring long-term impact and implementation at a global scale. Experts hope this will lead to the standardization of methodologies for tracking environmental influences on health, facilitating the development of precision medicine approaches tailored to an individual’s exposomic profile.
Tina Woods, steering committee member of the Exposome Moonshot Forum, CEO of Collider Health and executive director of the International Institute of Longevity, emphasized the urgency of this endeavor. “The time for the Human Exposome Project has come and I am excited to participate in the Exposome Moonshot Forum to move it from concept to reality,” she said. “We need to measure the exposome to demonstrate the return on investing in health and incentivising prevention.”
Professor David Furman, from the Buck Institute for Research on Aging and Stanford 1000 Immunomes Project, highlighted the technological advancements that make exposome research viable. “At a time of increasing environmental threats to human health such as air pollution and microplastics, we have the technologies like applied artificial intelligence to help us to unravel the complex interactions between environment, immunity and health at an individual level that can be aggregated up to get a true picture of the relative impact drivers of population health,” he said.
Efforts to systematically study the exposome have already begun in several cities worldwide. In the Netherlands, the Exposome-NL program in Rotterdam is one of the most comprehensive urban exposome initiatives, integrating environmental sensors with health records to assess how urban design impacts public health. Similarly, Utrecht’s Exposome-City program is pioneering bicycle-based mobile monitoring to track child-specific exposures, air quality variations, and the impact of urban gardening. Meanwhile, Barcelona’s Exposome Research Hub uses geospatial data and environmental sensors to link urban exposures – such as pollution and green space access – to respiratory and cardiovascular disease risk, directly informing policy decisions on urban planning and health equity; early findings have already influenced air quality and green space regulations in select districts [3].
Professor Nic Palmarini, director of the National Innovation Centre for Ageing, noted the potential of real-world testbeds for exposome research. “We have the technologies and tools to understand the human exposome with clinics, communities and cities acting as ideal real-world testbeds to understand what solutions will promote healthier behaviours and ultimately, outcomes,” he said.
The Human Exposome Project could provide critical data to guide national health policies and industry regulations; by understanding which environmental exposures are most harmful, governments can implement evidence-based interventions that reduce chronic disease prevalence and extend healthspan. Researchers are particularly interested in how different exposures interact – for example, how air pollution might compound the negative effects of poor diet or chronic stress; such insights could enable policymakers to design more targeted public health interventions.
Beyond environmental pollutants, emerging research suggests that psychosocial factors such as chronic stress, social isolation and early childhood adversity may have long-term biological consequences [4]. The integration of exposomic data with biological markers from genomics and metabolomics may allow for a more comprehensive understanding of how lifestyle and environmental exposures accelerate aging and disease processes.
As research continues to establish the specific pathways through which environmental factors influence aging and disease, there is an opportunity to embed prevention into the core of healthcare systems, reducing reliance on costly, reactive treatments. Healthcare systems could benefit from expanding their focus beyond clinical diagnostics to include real-time monitoring of environmental influences on health, leveraging wearable technologies and AI-driven analytics to provide more personalized recommendations.
With increasing recognition that environmental and behavioral factors outweigh genetic predisposition in shaping health outcomes, the exposome has emerged as a critical frontier in aging research. The challenge now is to translate these findings into actionable policy changes that prioritize longevity, resilience and quality of life on a societal scale. The Exposome Moonshot Forum could lay the foundation for a global strategy, translating exposomic insights into science-driven policies that promote healthier, longer lives.
READ MORE: Unveiling the exposome: How environmental stressors impact cardiovascular health
[1] https://www.nature.com/articles/s41591-025-03519-8
[2] https://www.sciencedirect.com/science/article/abs/pii/S026974912400472X
[3] https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-025-21835-z
[4] https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1429137/full
