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

Background: Epigenetic aging measures have promise as surrogate health outcomes in randomized control trials and observational cohort studies. The value of these measures, however, will reflect the extent to which they are associated with prospective health outcomes in real-world medical settings.

Methods: Using data from 2,216 post-9/11 veterans from the VISN 6 MIRECC's Post-Deployment Mental Health Study, we examined whether accelerated epigenetic aging, assessed by DunedinPACE, was associated with prospective chronic disease morbidity, predicted healthcare costs, and mortality over an average of 13.1 years of electronic health record follow-up.

Results: Veterans with faster DunedinPACE aging scores developed more chronic disease over the subsequent 5 years (RR, 1.25; 95% CI, 1.14-1.36), 10 years (RR, 1.31; 95% CI, 1.21-1.40), and 15 years (RR, 1.36; 95% CI, 1.22-1.52). Faster aging scores were also associated with increases in predicted healthcare costs over the next 5 years (β = 0.08; 95% CI, 0.03-0.13), 10 years (β = 0.23, 95% CI, 0.15-0.31), and 15 years (β = 0.21; 95% CI, 0.11-0.30). Faster DunedinPACE aging scores were associated with greater risk for incident myocardial infarction (84%), stroke (38%), diabetes (56%), cancer (25%), liver disease (44%), and renal disease (34%), as well as greater risk of mortality due to all-causes (38%) and chronic disease (74%). These results remained when adjusting for demographic, biomarker, and smoking covariates.

Conclusions: Our findings suggest DunedinPACE is a biomarker of accelerated aging that is prospectively associated with chronic disease morbidity and mortality, as assessed using health records from an integrated healthcare system.