Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality

Abstract

BackgroundWith two well‐validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes.MethodsData were from 405,944 adults (40–69 years) from UK Biobank (UKB) and 9972 adults (20–84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0–5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all‐cause mortality in UKB; CVD mortality, cancer mortality, and all‐cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed.ResultsThe unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: β = 0.741; NHANES: β = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all‐cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure—BioAgeAccel.ConclusionsAccelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality 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.

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“…Aging is a general biological phenomenon that affects all human beings and is characterized by a progressive loss of physiological integrity, leading to functional decline and increased risk of chronic ailments and death [5] . The population of older persons is one of the fastest-growing age groups, representing 10% of the global population in 2022 and expected to reach 16% by 2050, exceeding more than twice the number of children under the age of five and approximately the same as the number of children under the age of twelve [6] . Although aging is a natural and inevitable process, accelerated aging (i.e., when biological age exceeds chronological age) is a primary risk factor for chronic illness and mortality [7] .…”

The Association between Dietary Nutrient Intake and Acceleration of Aging: Evidence from NHANES

“…Studies have shown that accelerated aging is a significant risk factor for numerous diseases, including heart disease [ 6 ], chronic respiratory disease [ 7 ], depression [ 8 ], cancer [ 2 ], and others. Li et al discovered that accelerated aging could mediate the associations between unhealthy lifestyles and the risk of cardiovascular disease, cancer, and all-cause mortality [ 9 ]. Additionally, accelerated aging may result in a deterioration of physiological functions, such as impaired lung function [ 10 ].…”