Urban environment is linked to the regulation of gene expression

The study identified which factors present in urban environments are associated with DNA methylation, a mechanism that regulates gene expression. The results show that the same factors can have different effects at different stages of life.

As urbanisation increases, the role of the urban environment in shaping human health becomes ever more important, given the accompanying environmental and social factors. The aim of the researchers was to examine how air pollution, nighttime light, green spaces, and the overall level of urbanisation are related to DNA methylation patterns that regulate gene expression.

Jaanika Kronberg, a systems biology researcher who analysed Estonian Biobank data for the study, explains that DNA is like a recipe book, and DNA methylation is like sticky notes placed between the pages telling which recipes to use more or less. Because this mechanism is sensitive to environmental influences, it reflects our exposure to the external environment throughout life. However, disentangling the precise and distinct epigenetic effects of different environmental factors is challenging, as exposures often occur together.

International collaboration enables the study of large, life‑course‑spanning datasets

The analysis was based on data from several European cohort studies, involving more than 8,600 participants ranging from young children (ages 4–10) to older adults (up to 87 years old). Each participant’s living environment was used to estimate exposure to various urban factors. Blood samples provided by participants were used to investigate how these exposures may influence biological processes across the life course.

Collaboration among partners across Europe—from Estonia and Sweden to the Netherlands, Switzerland, and Germany—made it possible to study all life stages with sufficiently large sample sizes. “None of the participating cohorts covers all life stages, and often the dataset within a single cohort is not large enough,” Kronberg explained, highlighting the importance of international cooperation.

The study conducted within the EXPANSE project is also significant because of its reuse of existing data. All methylation datasets were generated in previous studies and were now analysed together with a new pan‑European environmental dataset. The study was led by researchers from the Helmholtz Centre in Munich.

Links between the external environment and the immune system

Among children aged 4–6, the clearest association between methylation changes and environmental exposure was with monthly nitrogen dioxide levels. This gas originates mainly from vehicle emissions and is one of the most characteristic pollutants in urban environments. When the same children were examined four years later, methylation differences were primarily linked to urbanisation. Interestingly, in both age periods, the same DNA regions were associated with urban‑environment factors, but with different specific exposures.

Adults showed the greatest number of DNA methylation changes, and these were linked to nearly all the factors studied. Some DNA regions were associated with multiple factors. This is logical, as older adults often have chronic conditions that make them more vulnerable to environmental influences.

Nitrogen dioxide and urbanicity-associated regions were enriched in genes from pathways related to the immune system in both children and adults.

Green spaces offer protection

Some of the most remarkable findings were the opposite‑direction associations between urban environmental factors and greenness in relation to methylation patterns. According to the researchers, green areas may provide biological protection against the urban stressors described above. This supports the idea that planning green spaces in cities is justified on health grounds and that urban planning should focus not only on reducing pollution but also on increasing green spaces.

Read more: https://doi.org/10.1016/j.ebiom.2025.106084