Stacey E. Alexeeff

Methylation of deoxyribonucleic acid (DNA) is an epigenetic regulator of gene expression that changes with age, but its contribution to aging-related disorders, including high blood pressure (BP), is still largely unknown. We examined the relation of BP to the methylation of retrotransposon sequences of DNA and of selected candidate genes. This investigation included 789 elderly participants in the Normative Aging Study, ranging in age from 55 to 100 years, who had longitudinal measurements of DNA methylation. In these subjects' DNA we measured the proportion of methylated sites in retrotransposable sequences and in pro-inflammatory genes, expressed as the percent of 5-methylated cytosines (%5mC) among all cytosines. From one to four methylation measurements were made for each subject between 1999 and 2009. We fit mixed-effects models, using repeated measures of BP as the outcome and DNA methylation as the explanatory variable, adjusting for confounding variables. We also fit a Bayesian mixed-effects structural equation model to account for heterogeneity in the effects of methylation sites within each gene. An increase in inter-quartile range (IQR) in the methylation of Alu elements was associated with an increase of 0.97 mm Hg in diastolic blood pressure (DBP) (95% CI 0.32-1.57), but no such association was observed for long interspersed nuclear element-1 (LINE-1). We also found positive associations between DBP and methylation of the genes for toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS), and a negative association between DBP and methylation of the gene for interferon-γ (IFN-γ). Associations between methylation and systolic blood pressure (SBP) were weaker than those between methylation and DBP. Bayesian mixed-effects structural equation model results were similar for both DBP and SBP models. The results of our study suggest that changes in DNA methylation of some pro-inflammatory genes and retrotransposable elements are related to small changes in BP.

Objectives Particulate air pollution is associated with cardiovascular events, but the mechanisms are not fully understood. The main objective was to assess the relationship between long-term exposure to traffic-related air pollution and blood pressure (BP). Methods The authors used longitudinal data from 853 elderly men participating in the Veterans Administration Normative Aging Study, followed during 1996–2008. Long-term average exposures to traffic particles were created from daily predictions of black carbon (BC) exposure at the geocoded address of each subject, using a validated spatiotemporal model based on ambient monitoring at 82 Boston-area locations. The authors examined the association of these exposures with BP using a mixed model. The authors included the following covariates: age, body mass index, smoking, alcohol, fasting glucose, creatinine clearance, use of cardiovascular medication, education, census-level poverty, day of week and season of clinical visit. Results The authors found significant positive associations between 1-year average BC exposure and both systolic and diastolic blood pressure. An IQR increase in 1-year average BC exposure (0.32 μg/m³) was associated with a 2.64 mm Hg increase in systolic blood pressure (95% CI 1.47 to 3.80) and a 2.41 mm Hg increase in diastolic blood pressure (95% CI 1.77 to 3.05). Conclusions Long-term exposure to traffic particles is associated with increased BP, which may explain part of the association with myocardial infarctions and cardiovascular deaths reported in cohort studies.

A peer-reviewed open access journal published by the National Institute of Environmental Health Sciences