Accelerated Aging Mediates the Associations of Unhealthy Lifestyles with Cardiovascular Disease, Cancer, and Mortality: Two Large Prospective Cohort Studies

Abstract

AbstractWith a well-validated aging measure – Phenotypic Age Acceleration (PhenoAgeAccel), this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9,972 adults (20-84 years) from US National Health and Nutrition Examination Surveys (NHANES). The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident cardiovascular disease, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (P values <0.001) in UKB, respectively. The mediation proportion of PhenoAgeAccel in associations of lifestyles with cancer mortality, and all-cause mortality were 25.7%, and 35.2% (P values <0.05) in NHANES, respectively. This study demonstrated that accelerated aging partially mediated the associations of lifestyles with adverse health outcomes in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late-life beyond lifestyle interventions.