Accelerated epigenetic aging and prospective morbidity and mortality among U.S. veterans.

Epigenetic measures of aging derived from DNA methylation are promising biomarkers associated with prospective morbidity and mortality, but require validation in real-world medical settings. Using data from 2,216 post-9/11 veterans, we examined whether accelerated DunedinPACE aging scores were associated with chronic disease morbidity, predicted healthcare costs, and mortality assessed over an average of 13.1 years of follow up in VA electronic health records. Veterans with faster DunedinPACE aging scores developed more chronic disease and showed larger increases in predicted healthcare costs over the subsequent 5, 10, and 15 years. Faster aging was associated with incident myocardial infarction, stroke, diabetes, cancer, liver disease, and renal disease, as well greater risk of mortality due to all-causes and chronic disease. These findings provide evidence that accelerated epigenetic aging is associated with worsening prospective health across multiple chronic diseases and organ systems assessed using electronic health records from an integrated healthcare system.