Fig. 4.

Higher biological age is associated with increased risk of premature dying and/or developing age-related chronic diseases. a-c) Comparison of predictive value of chronological and biological age for all-cause-mortality: people from 4th quartile of BA, but not chronological age, as well as people whose BA age is more than 7 years higher than their age (4th quartile) have more that 50% increased risk of premature dying. The ARIC study participants were divided in four quartile groups based on a) Age; b) Biological age (BA) calculated using nine biomarkers and on c) Difference between BA and Age (BA-Age). Left panels: Distributions of the study participants based on Age, BA and BA-Age with four quartile groups shown by different colors. Middle panels: Kaplan–Meier Survival Analysis. P values for difference between survival curves are shown (log-rank statistical analysis). People in 4th quartile of BA and BA-Age have higher mortality rate (pairwise multiple comparison of survival curves: ∗∗∗P < 0.0001 (Holm-Sidak method); . Right panels: Time-to-event analysis: COX proportional hazard models for all-cause mortality as outcome and four quartiles of Age, BA and BA-Age as exposure variables. The models are adjusted for age, sex, race and smoking status. See Table S5 for full models results. BA predicts mortality better than chronological age: age is no longer significant when BA is considered.d, e) Analysis of risk for chronic diseases in relation to BA: people whose BA is higher than chronological age (3rd and 4th quartiles) have up to 70% higher risk to develop chronic diseases.d) CIFs for diagnosis of first out of 4 diseases from set 1 constructed separately for four quartiles of BA-Age calculated from nine biomarkers. e) Time-to-event analysis: COX proportional hazard models for diagnosis of first disease as outcome and four quartiles of BA-Age as exposure variable. See also Fig. S4 for the same analysis performed for seven chronic diseases (set 2).