Lifestyle transitions and healthier biological aging in middle-aged and older adults: a prospective study in an East Asian cohort

Lifestyle modification is a key determinant of healthy aging; however, studies examining the associations between long-term lifestyle transitions and healthy aging remain limited. This prospective cohort study utilized a subset of participants from the Korean Genome and Epidemiology Study (KoGES). Lifestyle scores were derived from five modifiable behaviors: alcohol consumption, diet, physical activity, sleep, and smoking. Lifestyle transitions over 4- and 8-year intervals were classified as “Stable healthy”, “Improved”, “Worsened”, or “Stable poor”. Two healthy aging indices were assessed: (1) DNA methylation-based epigenetic age acceleration (EAA; PhenoAA, Grim2AA, and DunedinPACE) and (2) cardiovascular disease (CVD) risk, estimated using the Predicting Risk of CVD EVENTs equation (PREVENT) score. Associations were assessed via multivariable linear regression and generalized estimating equation models. Mediation analysis tested whether EAA mediated the association between lifestyle transitions and future CVD risk. This cohort study included 1020 participants (mean age 50.1 ± 8.2 years; 52.5% men). Compared with the “Stable healthy” group, participants with poor or worsening lifestyle patterns showed higher EAA. Over 8 years, EAA remained elevated in the “Improved” group (Grim2AA: β, 1.54; 95% CI 0.81–2.27; DunedinPACE: β, 2.20; 95% CI 0.38–4.02). EAA was higher in the “Worsened” (Grim2AA: β, 2.45; 95% CI 1.42–3.47; DunedinPACE: β, 2.81; 95% CI 0.25–5.37) and the “Stable poor” groups (Grim2AA: β, 3.81; 95% CI 3.11–4.52; DunedinPACE: β, 5.13; 95% CI 3.37–6.90). EAA partially mediated the association between lifestyle transitions and future CVD risk, accounting for 51.5–52.9% of the effect for Grim2AA and 15.2–15.7% for DunedinPACE. Unfavorable lifestyle transitions were associated with poorer healthy aging indices, and epigenetic aging partially mediated the association between lifestyle transitions and future CVD risk. These findings highlight the importance of early intervention and sustained healthy behaviors.