Epigenetic aging acceleration among World Trade Center-exposed community members

Aging is a complex biological process, and some individuals are aging faster or slower than expected. This phenomenon of aging acceleration occurs when biological age exceeds chronological age and can be assessed by epigenetic clock estimation. As aging acceleration is known to occur in response to some environmental exposures as well as trauma, we hypothesized that World Trade Center (WTC) exposures may have led to epigenetic aging acceleration. WTC-exposed women were selected from the World Trade Center Environmental Health Center (WTC EHC) clinic, with peripheral blood collected during routine clinical monitoring visits. The reference group was selected from the NYU Women's Health Study (NYUWHS), a prospective cohort study that collected blood samples before 9/11/2001. Epigenomes of WTC-exposed vs. unexposed women were profiled using the Infinium MethylationEPIC array. DNA-based epigenetic aging was estimated using Hannum, Horvath, PhenoAge and GrimAge epigenetic clocks. Age acceleration was defined as the residual from regressing estimated epigenetic age on chronological age. Ordinary least squares regression was used to investigate the relationship between WTC exposure and accelerated aging. After adjustment for race/ethnicity, smoking status, Body Mass Index (BMI), batch and cell type composition, WTC exposure was associated with epigenetic aging acceleration using the Hannum epigenetic clock (β_{WTC Exposed vs. Unexposed}: 3.789; p-value: <0.001). WTC exposure was also associated with epigenetic aging acceleration when using other epigenetic clock types (Horvath and PhenoAge, but not GrimAge), and when stratifying by breast cancer case (β_{WTC Exposed vs. Unexposed}: 3.473; p-value: <0.001) or cancer-free participant (β_{WTC Exposed vs. Unexposed}: 4.369; p-value: 0.001) status. Among all participants, having a breast cancer diagnosis was statistically significantly associated with accelerated aging (β_{Cancer vs. cancer-free}: 1.658; p-value: 0.021). WTC exposure is statistically significantly associated with epigenetic aging acceleration. This was true even after stratifying on cancer status. WTC exposure was positively associated with epigenetic aging acceleration in the overall cohort, among only those women who were cancer-free, and among breast cancer cases.