Accelerated aging modifies impact of ozone on QT interval and markers of inflammation in healthy humans
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Background/Aim: Older individuals often have increased health risks from environmental exposures, but this has been rarely investigated using molecular measures which reflect biological age. DNA methylation is a common means to measure biological age and difference between biological and chronological age (epigenetic age acceleration, EAA), is a mortality and chronic disease risk factor. However, we have yet to determine if EAA modifies responses to environmental exposure. Here, we investigated how EAA be a predictor of cardiovascular and inflammatory responses to ozone.
Methods: LAMARCK was a controlled exposure study where 17 healthy participants were exposed to 0.3-ppm ozone or to clean air for two hours in a randomized single-blind crossover study design. Inflammation and cardiac function measures were collected immediately before and 24-hours after exposures. Epigenetic age was estimated using the Horvath method from cells extracted from BALFs collected 24 hours after exposure. Here, we used linear regression models to examine if EAA (epigenetic age – chronological age) measured during air exposure is associated with the causal risk difference (CRD; Ozone – Clean Air) observed for clinical indicators of inflammation and cardiac function measured 24 hours after exposure. Outliers were removed using Cook’s distance and the standardized residuals. All outcomes were normalized to their pre-exposure values, and are presented as percentage of the mean value measured during air exposure.
Results: One-year EAA was associated with a 0.44% (95% confidence interval = 0.13%, 0.75%) increase in the CRD for QT interval in response to ozone exposure. EAA was also associated with a -15.3% (95% confidence interval = -23.2%, -7.41%) change in the CRD for C-reactive protein in response to ozone.
Conclusions: Accelerated aging in the lung is associated with worsened cardiac and depressed inflammatory responses to short-term ozone exposure. This work does not necessarily reflect the view or policies of the US EPA.