The Association of Epigenetic Age Acceleration and Multimorbidity at Age 90 in the Women’s Health Initiative

Abstract Background Epigenetic age acceleration (EAA), a measure of accelerated biological aging, has been associated with an increased risk of several age-related chronic conditions. This is the first study to prospectively examine the relationship between EAA and both multimorbidity count and a weighted multimorbidity score among long-lived postmenopausal women. Methods We included 1 951 women from the Women’s Health Initiative who could have survived to age 90. EAA was estimated using the Horvath pan-tissue, Hannum, PhenoAge, and GrimAge “clocks.” Twelve chronic conditions were included in the multimorbidity count. The multimorbidity score was weighted for each morbidity’s relationship with mortality in the study population. Using mixed-effects Poisson and linear regression models that included baseline covariates associated with both EAA and multimorbidity, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for the relationships between each EAA measure at the study baseline with both multimorbidity count and weighted multimorbidity score at age 90, respectively. Results For every one standard deviation increase in AgeAccelPheno, the rate of multimorbidity accumulation increased 6% (RR = 1.06; 95% CI = 1.01–1.12; p = .025) and the multimorbidity score by 7% (RR = 1.07; 95% CI = 1.01–1.13; p = .014) for women who survived to age 90. The results for a one standard deviation increase in AgeAccelHorvath, AgeAccelHannum, and AgeAccelGrim with multimorbidity accumulation and score were weaker compared to AgeAccelPheno, and the latter 2 did not reach statistical significance. Conclusion AgeAccelPheno and AgeAccelHannum may predict multimorbidity count and score at age 90 in older women and, thus, may be useful as a biomarker predictor of multimorbidity burden in the last decades of life.