A large prospective cohort study drawing on 181,955 participants from the UK Biobank has found that cardiovascular health and the pace of biological aging are jointly associated with the risk of developing chronic respiratory diseases, including chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis. The research, published in Clinical Epigenetics, also used genetic and epigenetic analyses to identify DNA methylation signatures that may connect these factors to disease risk.
The researchers assessed cardiovascular health using the Life’s Essential 8 score, a composite measure of cardiovascular health, and evaluated biological aging through phenotypic age acceleration, a measure of how much faster or slower a person is aging biologically compared with their chronological peers. Cox proportional hazards models were then applied to examine how these two measures relate to the risk of overall chronic respiratory disease and to each of the disease subtypes individually.
The results showed a consistent pattern. Higher phenotypic age acceleration was associated with increased risks of overall chronic respiratory diseases and of the individual subtypes, whereas a higher Life’s Essential 8 score was associated with lower disease risk. In other words, participants whose biological aging was running ahead of schedule faced greater respiratory disease risk, while those with better cardiovascular health faced less.
Joint analysis reinforced this picture. Participants who combined high cardiovascular health with a biologically younger status had the lowest risks of overall chronic respiratory disease and of each subtype examined. At the opposite end of the spectrum, additive interaction analyses indicated that the coexistence of low cardiovascular health and biologically older status conferred excess risks of overall chronic respiratory disease, COPD, and idiopathic pulmonary fibrosis beyond what would be expected from either factor alone.
Beyond these observational associations, the study turned to epigenetic mechanisms. The team performed epigenetic Mendelian randomization and colocalization analyses to prioritize DNA methylation CpG sites related to aging and to the Life’s Essential 8 score that are associated with COPD, asthma, and idiopathic pulmonary fibrosis. These analyses identified 287 aging-related and 42 Life’s Essential 8-related CpG sites as candidates linked to the three diseases.
To probe how these methylation marks might influence disease, the researchers conducted a three-stage Mendelian randomization analysis integrating DNA methylation, gene expression, and chronic respiratory disease risk. This analysis suggested that 14 CpG sites may influence disease risk through changes in the expression of 8 mapped genes, offering a possible regulatory pathway connecting cardiovascular health, biological aging, and respiratory disease development.
The authors conclude that these findings highlight the potential interplay between cardiovascular health, biological aging, and underlying epigenetic mechanisms in the development of chronic respiratory diseases and their subtypes. The study was designed as a large-scale prospective cohort analysis, which allows disease outcomes to be observed over follow-up rather than assessed at a single point in time, and the epigenetic components used genetic instruments to test potential causal directions.
As with any Mendelian randomization and colocalization work, the gene findings are described as suggestive rather than definitive: the three-stage analysis indicated that the 14 CpG sites may influence risk through the 8 mapped genes, and the prioritized CpG sites are candidates for further investigation. The article is published as an open-access, peer-reviewed accepted manuscript, a version that is subject to further edits before the final Version of Record appears. The work was conducted by Jian Liu, Liu-Dan Gu, Zheng-Qi Song, Yi-He Chen, and Yi-Jia Xiao, and appears in Clinical Epigenetics.
Subject of Research: Associations of cardiovascular health, biological aging, and blood DNA methylation with chronic respiratory disease risk in the UK Biobank.
Article Title: Dissecting the associations of cardiovascular health, biological aging, and blood DNA methylation signatures with chronic respiratory disease risk
Article References: Liu, J., Gu, L.-D., Song, Z.-Q., Chen, Y.-H., & Xiao, Y.-J. (2026). Dissecting the associations of cardiovascular health, biological aging, and blood DNA methylation signatures with chronic respiratory disease risk. Clinical Epigenetics. https://doi.org/10.1186/s13148-026-02248-0
Image Credits: AI Generated
DOI: 10.1186/s13148-026-02248-0
Keywords: cardiovascular health, biological aging, DNA methylation, chronic respiratory disease, COPD, asthma, idiopathic pulmonary fibrosis, UK Biobank, Mendelian randomization, epigenetics, Life's Essential 8, phenotypic age acceleration
News Source: Barbara Leach. (October 28, 2026). Heart health, biological aging, and DNA methylation linked to chronic respiratory disease risk. Scienmag.
