The Innovation

Particulate matter exposure has a direct impact on airways diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and over the next 30 years, rising particulate air pollution is expected to increasingly affect disease outcomes. We identified transcriptional mechanisms of particulate exposure in the airway epithelium that connect with disease risk using genetics and multiomics. We first defined and compared rapid-transient nascent transcription responses across particulate exposures. Using hyaluronic acid metabolism as a prototype, we showed that rapid-transient responses to particulates were relevant to steady-state mRNA expression and COPD pathobiology. We then found genetic links between nascent transcription responses and asthma or COPD risk by associating single nucleotide polymorphisms (SNPs) with disease in the All of Us study. By combining nominal association statistics, pre- and post-association filters, and rigorous external validation, we identified SNPs associated with disease across multiple ancestries and cohorts. We then derived epigenetic and gene regulatory mechanisms from these SNPs. Our results highlighted plausible transcriptional mechanisms of disease, such as regulation of TOMM7 expression by rs13243243. By applying detailed transcriptional analysis to study particulate exposures, we identified novel SNPs and genes that define gene-environment interactions for airways disease.

Open air burn pits were used extensively during military operations in Iraq and Afghanistan, potentially exposing millions of US Veterans to toxic airborne hazards. Many of the airborne toxins released have been shown to induce lung inflammation and lung injury and are mutagenic. This is the first large-scale study of associations between self-reported burn pit exposures and the development of cancer. Using data from the Airborne Hazards and Open Burn Pit Registry, we found that Veterans reporting burn pit exposures are associated with a higher odds of developing cancer. However, investigations into the development of specific type of cancer and into a burn pit exposure dose-response effect were inconclusive.

Background: Climate mitigation policies can lower air pollutant concentrations and deliver substantial health co-benefits. The French Ecological Transition Agency (ADEME) proposed four contrasting Transitions 2050 net-zero scenarios. We quantified mortality, morbidity, and health-economic co-benefits from projected PM2.5 and NO2 reductions across all four scenarios in continental France. Methods: Emission projections were input to the CHIMERE chemistry-transport model to estimate PM2.5 and NO2 concentrations for 2030 and 2050. Health impacts were assessed using disease-specific cessation-lag assumptions relative to 2019, covering premature mortality, morbidity, DALYs, and economic benefits across nine outcomes (hypertension, lung cancer, ischaemic heart disease, stroke, COPD, type-2 diabetes, acute lower respiratory infections, and asthma in children and adults). Findings: Population exposure is projected to decline by about 40% for PM2.5 and 70% for NO2 by 2050, with health gains remaining substantial and broadly equivalent across all four scenarios and modest differences between sufficiency-oriented and technology-driven pathways. Under delayed-impact assumptions, avoided premature deaths ranged from 21,300 to 22,100 for PM2.5 and 24,500 to 26,200 for NO2. Morbidity and disability-adjusted life year (DALY) reductions, as well as economic savings, spanned similarly; total avoided morbidity cases were 84,000-88,000, direct medical cost reductions were e1.0-1.1 billion/year, and intangible cost savings of e41-43 billion and e36-39 billion, respectively. Interpretation: Health co-benefits are substantial, consistent across contrasting scenarios, and increase markedly from 2030 to 2050. Explicitly incorporating these co-benefits into climate policy appraisals may strengthen the case for ambitious mitigation and improve decision-maker acceptability.

Environmental exposures are increasingly examined in relation to mental health, yet large-scale epidemiological analyses remain constrained by fragmented geospatial data, heterogeneous spatial and temporal resolutions, and privacy-preserving linkage requirements, limiting systematic investigation of multiple environmental domains at the population level. We present environMAP, a harmonised set of analysis-ready environmental exposure layers derived from open, global sources. environMAP spans the built environment, green and blue spaces, light exposure (solar radiation and night-time light), terrain, weather and extremes, and air pollution. We document data provenance, spatial buffers, preprocessing, projection alignment, and metadata, and provide a reproducible workflow for privacy-preserving linkage to cohort residential locations. To demonstrate utility, we linked environMAP to >200,000 adults in the German National Cohort (NAKO) and summarised self-reported lifetime doctor-diagnosed depression across exposure gradients using sex-stratified descriptive analyses. Gradients were interpretable and broadly consistent with prior evidence, supporting feasibility, scalability, and hypothesis generation. The framework is adaptable to other outcomes, cohorts, and regions.

Fine particulate air pollution (PM2.5) in the United States has fallen by roughly half since 2000, yet linked health outcomes such as diabetes and childhood ADHD have not improved in parallel. One reconciling possibility is that pollution exposure in early life produces health effects that emerge only years or decades later, after pollution itself has declined. Using two decades of U.S. county-level data, we relate annual PM2.5 estimates to birth outcomes, diabetes prevalence, and small-area estimates of childhood attention-deficit/hyperactivity disorder (ADHD) across short and long time scales. Within counties, changes in low birth weight rates are associated with changes in PM2.5 during the same year and the year prior to birth. At longer time scales, cross-county comparisons show that PM2.5 exposure is associated with higher prevalence of adult diabetes and ADHD after approximately a decade. Together, these patterns suggest that population-level health risks from air pollution may persist over decades, even as pollution itself declines.

Background Wildfire activity and smoke exposure are increasing worldwide because of climate and land-use change. Although fine particulate matter (PM2.5) may impair pulmonary immune defences against tuberculosis (TB), population-level evidence remains limited. We estimated the effect of wildfire-related PM2.5 exposure on TB notification rates in Brazil. Methods We conducted a nationwide panel study linking municipality-level monthly TB notifications from Brazil's SINAN system with wildfire-related PM2.5 estimates from GEOS-Chem simulations across 5,545 municipalities (2003-2023). We estimated the impact of high-exposure days (PM2.5 > 25 g/m3) on monthly TB notifications using Poisson regression with fixed effects for municipalities, state-by-year, and state-by-month, controlling for time-invariant differences, secular trends, and seasonality. Distributed lag effects were estimated over 1-24 months before notification. Models accounted for meteorological conditions, GeneXpert diagnostic coverage, and spatial correlation using Conley standard errors. We computed attributable fractions among exposed municipality-months (AFE). Sensitivity analyses evaluated alternative PM2.5 thresholds (15 and 35 g/m3), co-pollutants, and agricultural expansion. Findings From Jan 1, 2003 to Dec 1, 2023, 1,758,982 TB cases were reported. Of these, 353,319 (20.1%) had at least one high-exposure day (PM2.5 > 25 g/m3) 1-24 months before notification. An additional 14 high-exposure days over the 24-month lag period was associated with an average monthly increase of 2.9% [95% CI: 0.9-4.9%] in TB notification rates. Effects peaked at 13 months (IQR: 11-14) prior to notification. Results showed a dose-response relationship across PM2.5 thresholds and were robust to controlling for NO2, O3, and agricultural expansion. Overall, wildfire-related PM2.5 exposure accounted for 2.1% [0.7-3.5%] of TB notifications in exposed municipality-months, corresponding to 7,802 [2,612-12,544] attributable cases. The AFE reached 10.7% [7.1-14.0%] in Pantanal and 7.3% [6.1-8.5%] in Amazonia, areas most impacted by wildfires. Interpretation Wildfire-related PM2.5 exposure may represent an increasingly important and modifiable risk factor for TB. As wildfire activity increases across many regions of the world, these findings highlight the need for integrating air quality into climate adaptation and TB control strategies.

Air pollution has well-documented negative cardiovascular and respiratory consequences. However, the impact of particulate matter pollution (PM2.5) on brain development is unclear. Animal studies suggest that exposure to early-life PM2.5 can cause adverse neurodevelopmental outcomes, but in vivo human work has been hampered by cross-sectional designs and heavily confounded PM2.5 exposure measures. Here we use an innovative natural experimental design to isolate the effects of wildfire pollution on neurocognitive development in a large cohort of children (N>9000, 4 waves, age 9-16). Doing so, we find that greater wildfire PM2.5 exposure is robustly associated with slower brain development and shallower cognitive improvement across early adolescence. Our study underscores the urgent public health concern that wildfire PM2.5 poses for childhood development.

While exposure to volatile organic compounds such as ethylene dichloride and vinyl chloride monomer is a well-established cause of liver disease, particularly hepatic hemangiosarcoma, characterizing real-world exposure profiles in communities surrounding industrial centers remains challenging. Calvert City, Kentucky (population ~2,500), provides a unique setting characterized by both active industrial emissions and legacy sources of air toxics. To address these complexities, this method paper describes the framework for the Biomonitoring and Environmental Assessment for Community Outreach and Neighborhood Safety (BEACON) study. By utilizing a novel, multi-dimensional exposure assessment strategy, BEACON aims to characterize air toxic exposures and provide actionable data for community health and safety. For the BEACON study, we will leverage Kentucky Department of Air Quality measures of air toxics, analyze urine samples in a small cohort of community volunteers, analyze community urine via wastewater in an adjacent community, geocode citizen odor reporting, assess blood markers in wildlife, survey small and large animal veterinarians in the area for anomalies in morbidity and mortality, and work with the regional health system to enhance vigilance for health issues associated with toxicants present in the area. In addition, blood samples will be collected at three time points and biobanked for future analyses. Efforts will be made to link this study to additional large-scale long-term cohorts where possible. Throughout the project, community engagement will play a critical role by raising awareness, fostering collaboration, and ensuring that the voices of affected residents are heard.

This study aimed to clarify aerosol exposure risks throughout the workflow of a Biosafety Level 2 (BSL-2) polymerase chain reaction (PCR) laboratory, validate the suitability of the {Phi}X174 bacteriophage as an indicator virus, and provide evidence for biosafety control measures. The {Phi}X174 bacteriophage was used to simulate viral samples, and a concentration-bacteriophage plaque standard curve was constructed (R2=0.998). Five operational steps in a simulated PCR laboratory were quantitatively monitored for aerosol concentration using double-layer agar plates, with blank controls used to eliminate interference. Statistical analysis was employed to identify risk differences. Sample homogenization ((5.67 {+/-} 1.23) x 104 plaque-forming units (PFU)/m3) and nucleic acid extraction ((3.45 {+/-} 0.89) x 104 PFU/m3) were identified as high-/very high-risk steps. The viral load in the samples was strongly positively correlated with the aerosol concentration (r = 0.926, P <0.001), with aerosol levels linearly decreasing with increasing distance in high-risk steps. The {Phi}X174 bacteriophage demonstrated high detection sensitivity (101 PFU/ml) and demonstrated safety compatibility with BSL-2 laboratories. Aerosol risks in PCR laboratories exhibit step-specific differentiation, and {Phi}X174 serves as an ideal indicator virus. Proposed strategies such as equipment upgrades and personal protective equipment (PPE) grading can reduce exposure risks.

Human metapneumovirus (HMPV) causes acute lower respiratory infections, primarily affecting young children and older adults, with seasonal outbreaks peaking annually in March or April in the United States and other temperate regions in the Northern hemisphere. However, the factors driving HMPV seasonality in the United States remain poorly understood. We analyzed laboratory-confirmed HMPV cases and age-specific emergency department visits across 10 US regions, fitting an age-stratified dynamic transmission model to assess spatiotemporal patterns and investigate the influence of environmental variables and viral interference from RSV on HMPV transmission rates. We found that models incorporating climate variables into the transmission rate, including vapor pressure, precipitation, potential evapotranspiration, and minimum temperature, could not capture the timing of HMPV activity across all regions. Instead, HMPV timing was associated with RSV activity, with the HMPV transmission rate reduced in the presence of RSV. We showed that, unlike RSV, only models incorporating viral interference could reproduce the biennial pattern of HMPV observed in some regions, characterized by alternating late-small and early-large epidemics. Furthermore, our model successfully reproduced post-COVID-19 HMPV and RSV epidemics and predicted that RSV interventions are not likely to lead to a substantial increase in HMPV activity despite decreasing competition from RSV. Our work unravels the spatiotemporal dynamics of HMPV and its interaction with RSV, informing future seasonal forecasting and intervention strategies for HMPV.

Background: Lead exposure is estimated to cause approximately 3.5 million premature deaths a year, yet the key ongoing sources of lead exposure are unclear. Methods: We estimated the contribution of dietary lead intake to global blood lead levels (BLLs) for 7-year-old children and 22-year-old adults by applying the All-Ages Lead Model (AALM) to calculate blood lead levels (BLLs) based on 25 total diet studies (TDS) that quantify dietary lead intake across 46 countries. Results: For children, the population-weighted average dietary lead intake in low- and middle-income countries (LMICs) (32.0 g/day) was found to be more than three times higher than in high-income countries (HICs) (9.3 g/day), and more than 10 times higher than the FDA reference level for children (2.2 g/day). The average impact on BLLs for children is estimated to be near 29 g/L in LMICs and near 12 g/L in HICs. Averaged across the TDS data, vegetables (27%) and cereals (24%) were found to contribute the most to dietary lead. Conclusions: While there are limitations associated with biokinetic modelling and the TDS data from LMICs, these results suggest that the contribution of dietary lead intake to global lead exposure is in the region of 40 to 50%, suggesting, in turn, that dietary lead intake is likely a major global driver of lead poisoning. Lead absorbed from the environment into food crops is expected to be the key driver of dietary lead. Current regulatory levels for maximum lead concentrations in foods (0.05-0.3 mg/kg) are out-of-date and may imply a dietary lead intake of 200 g/day, far higher than the FDA reference level (2.2 g/day). Collecting representative TDS data in high lead burden countries should be a priority. Further research is also recommended on upstream lead sources and pathways of lead uptake in plants, driving global food contamination.

Tomato yellow leaf curl virus (TYLCV) is a devastating viral pathogen threatening agricultural crops globally. In this study, we identified a novel TYLCV isolate (TYLCV-YN6244), which caused viral epidemic in resistant tomato cultivars at Yuanmo county, Yunnan Province of China. We determined the complete genome of TYLCV-YN6244 and found it encoded six viral proteins characteristic of Geminivirus. We identified its V2 protein as a potent viral suppressor of RNA silencing (VSR), and generated infectious clone of wildtype TYLCV-YN6244, or V2-defective TYLCV-YN6244 (TYLCV-YN6244-{Delta}V2) in which V2 was deleted. Both of infectious clones were capable of systemically infecting tobacco and tomato. However, TYLCV-YN6244 but not TYLCV-YN6244-{Delta}V2 could cause disease symptoms in wildtype tobacco or tomato plants, and viral accumulation was drastically reduced in plants infected with TYLCV-YN6244-{Delta}V2 compared to TYLCV-YN6244 while the efficiency of virus-derived small interfering RNAs (vsiRNAs) biogenesis was conversely increased in plants infected with TYLCV-YN6244-{Delta}V2. Surprisingly, small RNA profiling indicated that 21nt and 22nt rather than 24nt vsiRNAs were predominantly produced in tomato plants infected with either TYLCV-YN6244 or TYLCV-YN6244-{Delta}V2. Furthermore, transcriptome analyses revealed that TYLCV-YN6244 or TYLCV-YN6244-{Delta}V2 infection differentially modulated metabolism and defense-related pathways in tomato, probably underlying distinct viral pathogenicity and disease symptoms induced in plants. Overall, our research not only identified a novel pathogenic TYLCV isolate but also characterized molecular biology and host response in tomato with infectious clones firstly developed, with implications in untangling virus-host interaction for developing novel resistance in crop tomato.

Background: Lung cancer in never-smokers is rising, with a substantial proportion harboring the EGFR mutation. While fine particulate matter (PM2.5) is a recognized risk factor, other intervenable pollutants and built environmental factors remain unknown. Objectives: To identify urban characteristics associated with EGFR-mutant (vs. wild-type) lung cancer using high-resolution spatiotemporal data. Methods: We analyzed 2,699 lung cancer patients with documented EGFR status treated at a high-volume academic medical center in New York City. Patient residential addresses were linked to high-resolution (300m x 300m) 5-year cumulative exposures to 3 air pollutants and 26 urban features. We developed Light Gradient Boosting Machine (LightGBM) models to classify EGFR status, comparing a basic clinical model with established predictors (Asian, female, never-smoking status, and adenocarcinoma histology) to an extended model with additional urban factors. Predictive performance was assessed based on discrimination (AUC). Results: We included 2,699 patients, of whom 54.1% were female and 25.8% self-identified as Asian, 11.2% as Black, and 7.4% as Hispanic; and 29% had EGFR-mutated cancer. The extended model showed modest improvements in discrimination (AUC: 0.775 [95% CI, 0.739-0.809] vs. 0.768 [0.723-0.811]), compared to the clinical model. Newly identified factors for EGFR-mutant status included black carbon (BC), nitrogen dioxide (NO2), proximity to airports, reduced access to public transportation, elevated noise levels, and lead exposure. Conclusions: Traffic-related pollutants (BC, NO2) from diesel engines and motor vehicles, and proximity to airports, were among the novel spatiotemporal features associated with EGFR-mutant lung cancer. These results may inform policy interventions.

Identifying the origin of an emerging epidemic wave within days of onset could enable targeted response before national spread, yet current methods rely on genomic sequencing that lags clinical detection by 2-4 weeks. We analysed daily COVID-19 cases from Japan's 47 prefectures across eight waves (2020-2023), aggregated into 11 regional blocks. Wave onset was defined by the first difference of the K-value (K'). Six surveillance indicators were evaluated with and without cumulative historical weighting ({lambda} = 0.75) and benchmarked against a large language model (Claude Haiku), scored by F1 against genomically confirmed origins. At 14 days after onset, cumulative weighting of peak and cumulative incidence (B1+prior, B3+prior) reached mean F1 = 0.622, exceeding the model (0.524); the gap was largest in Wave 7 (1.000 vs 0.333). Simple cumulative weighting of routine surveillance data identified wave origins more accurately than a language model, without proprietary tools or sequencing.

Background: Surgical care centralization in the U.S. delays access and increases carbon emissions. Global targets suggest patients live within 2-hours of a surgical facility. This study quantifies the environmental impact of travel for cataract surgery in rural Michigan and models the potential emissions reductions from decentralizing surgical and follow-up services. Methods: A retrospective, cross-sectional study analyzed electronic medical records from a rural Michigan ophthalmology practice (March-November 2023). We calculated travel distances using population-weighted centroids and estimated emissions using U.S. Department of Energy vehicle data. A k-means clustering model optimized additional facility placement, and a gradient analysis identified optimal numbers for decentralization points, for emissions reductions. Results: The 920 patients traveled a median of 55.45 km (IQR: 43.33-88.20 km) for surgery and 55.07 km (IQR: 43.54-87.82 km) for follow-up visits, generating Total Surgical Access Emissions (TSAE) of 57,168 kgCO2; (median of 59.20 kgCO2; IQR: 32.31-81.87) under the centralized model. The k-means decentralization model and gradient analysis identified 7 hospitals and 9 clinics, respectively, as the optimal expansion points, reducing emissions by 34.07% (19,475 kgCO2 saved) and 39.52% (22,590 kgCO2; saved). The Surgical Access Carbon Impact (SACI) model demonstrated that achieving two-hour access to clinic services reduced excess emissions by 54.7%. Sensitivity analyses using fuel-efficient vehicles (Toyota Prius and Tesla Model 3) or reducing follow-up visit frequency reduced emissions by 54.03% (30,888 kgCO2) and 25.83% (14,768 kgCO2), respectively. Conclusion: Decentralizing surgical services in rural U.S. settings could cut travel-related emissions by up to 40%, significantly reducing healthcare-related carbon footprints while improving timely access to care. The SACI metric provides a novel framework for integrating environmental sustainability into U.S. health policy and service planning

Background: Randomized controlled trials have shown that computed tomographic (CT) screening reduces lung cancer mortality. Improved identification of at-risk groups, by leveraging non-smoking risk factors, could help refine screening selection. Aim: To evaluate polygenic risk scores (PRSs) and ambient air pollution (AAP) exposure for risk stratification in the NELSON lung cancer screening cohort. Methods: Two PRSs (PRS-McKay/PRS-Byun) and several AAPs (including nitrogen dioxide, ozone, and particulate matter [PM]) were assessed in the NELSON lung cancer screening trial (N=7,364). PRSs were validated in the Rotterdam Study (N=11,493). Associations with lung cancer, mortality, screening results, and discriminative ability to distinguish lung cancer were evaluated. Results: PRS-McKay and PRS-Byun were associated with lung cancer (odds ratio [OR] per SD [95%CI]: 1.22 [1.08-1.37] and 1.28 [1.13-1.44], respectively) and lung cancer-specific mortality (OR [95%CI]: 1.24 [1.05-1.47], for both), but not with non-lung cancer mortality (OR [95%CI]: 1.01 [0.94-1.10] and 1.03 [0.95-1.12], respectively). Exposure to PM2.5 was associated with lung cancer (OR [95%CI]: 1.11 [1.01-1.22]). PM constituents were associated with adenocarcinoma, particularly PM10 (OR [95%CI]: 1.16 [1.01-1.32]) and ultra-fine particles (OR [95%CI]: 1.16 [1.04-1.30]). PRS and AAP added modestly to the discriminative ability for lung cancer on top of pack-years, age, and sex (area under the curve [95%CI]: 0.659 [0.624-0.695] vs. 0.643 [0.608-0.679]). Conclusions: PRSs and exposure to PM were associated with lung cancer in a high-risk screening population. The primary potential of PRSs may reside in refining lung cancer screening selection toward individuals at higher risk of dying from lung cancer specifically.

Here, we present the first graph-based Korean Pangenome Reference (K-PanRef), constructed from 14 healthy Korean individuals. K-PanRef comprises 13 high-quality diploid Korean genome assemblies (mean QV ~62.0) and KOREF1-G-TTAGGA, the first complete Korean reference genome. Integration of these assemblies generated a ~3.2-Gb pangenome graph containing ~39.3 million nodes and ~53.8 million edges, with the accumulation of common sequences (frequency [&ge;]10%) reaching a plateau. Additionally, K-PanRef contains ~4.3 million Korean-specific small variants and ~76.0 thousand Korean-specific SVs absent from the Chinese and human pangenome references, improving the representation of Korean genetic diversity relative to these references. To evaluate its utility for short-read-based SV analysis, we genotyped 75 whole-genome sequencing (WGS) samples, including 15 patients with early-onset myocardial infarction (MI). Although constructed entirely from healthy genomes, K-PanRef supported the identification of putative disease-relevant SVs in this exploratory application. K-PanRef-based genotyping identified ~95.6 thousand small variants and 820 SVs observed only in the early-onset MI samples. Among the early-onset MI-group SVs, 491 were absent from public databases, suggesting that they may represent previously unrecognized candidate variants related to early-onset MI. Of these, 164 SVs overlapped 134 genes, of which 89 had reported associations with 42 cardiovascular diseases or traits, including eight genes previously linked to MI. Together, these results establish K-PanRef as a valuable resource for representing Korean genetic diversity and enabling more comprehensive discovery of population-specific and novel putative disease-relevant variants from short-read sequencing data.

Introduction Air pollution is a leading driver of cardiovascular disease with a growing body of literature implicating this in worse glucose homeostasis. Increases in fine particulate matter air pollution (PM2.5) are associated with increased blood glucose and hemoglobin A1c across the glycemic spectrum from normoglycemia to prediabetes to all forms of diabetes. Despite strong evidence for positive associations of PM2.5 with dysglycemia, it remains unknown if reducing air pollution exposure through air filtration can effect improvements in glucose. This study aims to test the hypothesis that short-term, in-home air pollution reduction using high efficiency particulate air (HEPA) filtration will improve blood sugar in adults with prediabetes. Methods and analysis This trial is a randomized, double-blind, sham-controlled trial of the effects of lowering air pollution exposure using HEPA filtration on cardiometabolic health in adults with prediabetes living in the New York City area. Participants will be randomly assigned to use bedroom air cleaners, or sham air cleaners, while measuring PM2.5 continuously for 1 month. The primary outcomes will be continuous glucose monitoring metrics measured before and after HEPA air filtration. Exploratory outcomes will include insulin resistance measures, serum biomarkers and transcriptomics measured before and after HEPA intervention. We will quantify effects of HEPA filtration with models using treatment arm (true versus sham filtration) as the independent variable. Secondary analyses will model continuous measures of PM2.5 as the independent variable. Ethics and Dissemination This study has undergone peer review; and the work was supported by Grant 2023-0214 from the Doris Duke Foundation, who had no other role in study design or implementation. The study was registered in ClinicalTrials.gov (NCT05994937) prior to recruitment. Clinical Trials Clinical Trials NCT05994937; https://clinicaltrials.gov/study/NCT05994937

Background Increasingly accessible satellite imagery provides scalable measures of the built and natural environment relevant to population health. However, whether such imagery can capture subnational variation in mortality and life expectancy remains unclear. We therefore assessed its predictive value for regional mortality and life expectancy across OECD regions. Methods We conducted an ecological, cross-sectional prediction study using 2023 data from OECD Territorial Level 3 (TL3) regions. Annual cloud-masked composites from the Harmonized Landsat and Sentinel-2 collection were processed in the Google Earth Engine, tiled at 224 x 224 pixels, and encoded with the pretrained Prithvi foundation model to derive region-level satellite embeddings. For each outcome, we trained LightGBM regressors for a country-only baseline, a satellite-only model, a combined model (country + satellite), and a final contextual model that additionally included prespecified socioeconomic and environmental covariates. Performance was evaluated using 10-fold outer cross-validation with held-out test folds; R2 was the primary metric. Results The analytic sample comprised 2,414 OECD TL3 regions across 38 countries, for which 939,959 satellite image tiles were processed. In paired bootstrap comparisons, adding satellite features to country indicators improved predictive performance for all outcomes, with incremental R2 ranging from 0.097 to 0.233. The final contextual model achieved R2 values of 0.78 (95% CI, 0.74-0.81) for crude mortality, 0.87 (0.84-0.89) for age-adjusted mortality, 0.86 (0.82-0.88) for infant mortality, and 0.76 (0.69-0.84) for life expectancy. In SHAP analyses, the aggregated satellite image effect consistently ranked among the top predictors across outcomes. Conclusion Satellite imagery captures subnational environmental heterogeneity relevant to regional mortality and life expectancy beyond country identity alone. Earth observation may therefore provide a scalable, complementary data source for characterizing geographic disparities in population health.

Environmental exposures are major modifiable determinants of human aging, yet the evidence remains fragmented across organ-agnostic summaries and rarely confronts population inequity. Here we present an exposomic atlas of pan-organ aging in ~300,000 UK Biobank adults, mapping 164 environmental and behavioural exposures onto biological aging of the whole body and nine organ subsystems. Comprising 1,476 systematically tested exposure-subsystem associations, the atlas reveals that environmental effects on human aging are pervasively organ-specific, with 65.9% of exposures acting divergently across organ subsystems. This landscape resolves into nine navigable modules that preserve organ selectivity, predict 23 major age-related diseases, and expose distinct dimensions of health inequity. In-silico analyses further show that priorities for ameliorating aging are target-dependent rather than universal, diverge markedly from the whole-body ranking (Kendall's {tau} = 0.52 to 0.39), reorder substantially across population strata, with findings externally validated in an ethnically distinct cohort. The atlas establishes an organ-resolved and target-aware foundation for precision environmental health.