Phenotypic age mediates effects of life's essential 8 on reduced mortality risk in U.S. Adults

Abstract

Abstract Objective This study aimed to find out whether phenotypic age could mediate the protective effects of healthy lifestyles on mortality. Methods We included adult participants with available data for individual PhenoAge and LE8 scores from the National Health and Nutrition Examination Survey 2005–2010 (3 cycles) and linked mortality records utill Dec 31, 2019. Adjusted hazard ratios (HR) were estimated to evaluating the associations of PhenoAge and LE8 scores with all-cause and cardiovascular mortality risk. Mediation analyses were performed to estimate the proportional contribution of PhenoAge to the effect of LE8 on mortality risks. Results One-year increment in PhenoAge was associated with a higher risk of all-cause (HR = 1.04 [95% CI, 1.04–1.05]) and cardiovascular (HR = 1.04 [95% CI, 1.04–1.05]) mortality, independent of chronological age, demographic characteristics and disease histories. High level of LE8 (score: 80–100) was associated with a 3.30-year younger PhenoAge. PhenoAge was estimated to mediate 36% and 22% of the effect of LE8 on all-cause and cardiovascular mortality, respectively (all P < 0.001). As for single-metric scores of LE8, PhenoAge mediated 30%, 11%, 9%, and 7% of the effects of the healthy diet, smoking status, blood pressure and physical activity on all-cause mortality risk, respectively (all P < 0.05). Conclusion Adherence to LE8 recommendations slows phenotypic aging. PhenoAge could mediate the effect of LE8 on mortality risk.