Epigenetic Age Acceleration Correlates with Increased Mortality
Epigenetic clocks are produced by the application of machine learning techniques to epigenetic data obtained from people at various ages. Characteristic changes in DNA methylation take place with advancing age, and thus can be used to provide an assessment of biological age. Epigenetic age acceleration is the state of having an epigenetic age, as measured by an epigenetic clock, that is higher than chronological age. Numerous studies have shown that this acceleration correlates with a higher risk of age-related disease and mortality.
We analyzed data from 2,105 participants to the 1999-2002 National Health and Nutrition Examination Survey aged ≥50 years old who were followed for mortality through 2019. Epigenetic age accelerations (EAAs) were calculated from Horvath, Hannum, SkinBlood, Pheno, Zhang, Lin, Weidner, Vidal-Bralo and Grim epigenetic clocks regressed on chronological age. Using cox proportional hazards regression, we estimated the hazard ratio (HR) for the association of EAA (per 5-year) and the DunedinPoAm pace of aging (per 10% increase) with overall, cardiovascular, and cancer mortality, adjusting for covariates and white blood cell composition.
During a median follow-up of 17.5 years, 998 deaths occurred, including 272 from cardiovascular disease and 209 from cancer. Overall mortality was most significantly predicted by Grim EAA (HR: 1.50) followed by Hannum (HR: 1.16), Pheno (R: 1.13), Horvath (HR: 1.13) and Vidal-Bralo (HR: 1.13) EAAs. Grim EAA predicted cardiovascular mortality (HR: 1.55), whereas Hannum (HR: 1.24), Horvath (HR: 1.18) and Grim (HR: 1.37) EAAs predicted cancer mortality. DunedinPoAm pace of aging was associated with overall (HR: 1.23) and cardiovascular (HR: 1.25) mortality.