Accelerated transcriptomic age and susceptibility to traffic-related air pollution among cardiac catheterization...

Accelerated transcriptomic and/or epigenetic age have been proposed as biomarkers of disrupted systemic health and of increased sensitivity to environmental exposures. Previously, we observed epigenetic age acceleration as a biomarker of sensitivity to air pollution, especially for traffic-related air pollution (TRAP) in urban cohorts.

Using 1024 participants from the CATHGEN cohort, we evaluated whether increased cardiovascular risk associated with TRAP was modified by transcriptomic aging. Residential proximity to major roadways was the measure of TRAP and peripheral arterial disease (PAD) and blood pressure were outcomes. Blood-based gene expression-based age acceleration (GEXAge AAD) and Horvath epigenetic age acceleration (DNAmAge AAD) were measures of age acceleration, and models were adjusted for chronological age, race, sex, smoking, socioeconomic status, body mass index, hyperlipidemia, and diabetes.

We observed significant interactions between TRAP and GEXAge AAD and DNAmAge AAD, but these interactions were weaker than in previous analyses including only urban communities. Constraining the cohort to those residing in more urban environments strengthened the interaction between GEXAge AAD and TRAP. Interactions indicated that increased transcriptomic or epigenetic age elevated associations between proximity to roadways and PAD; the strongest interactions were identified in individuals with both accelerated epigenetic and transcriptomic age. Exploratory sex-stratified analyses identified potentially stronger associations in males, but these results would require further validation in larger studies.

Similar to epigenetic age, elevated transcriptomic age may be an indicator of increased TRAP sensitivity. Individuals with jointly elevated epigenetic and transcriptomic age may have greater environmental health risks than those with elevated transcriptomic age alone.