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

Xueqin Li; Xingqi Cao; Jingyun Zhang; Jinjing Fu; Mayila Mohedaner; Danzengzhuoga; Xiaoyi Sun; Gan Yang; Zhenqing Yang; Chia-Ling Kuo; Xi Chen; Alan A Cohen; Zuyun Liu

doi:10.1111/jgs.18611

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

J Am Geriatr Soc. 2024 Jan;72(1):181-193. doi: 10.1111/jgs.18611. Epub 2023 Oct 4.

Authors

Xueqin Li¹, Xingqi Cao¹, Jingyun Zhang¹, Jinjing Fu¹, Mayila Mohedaner¹, Danzengzhuoga¹, Xiaoyi Sun¹, Gan Yang¹, Zhenqing Yang¹, Chia-Ling Kuo², Xi Chen^{3

4}, Alan A Cohen^{5

6}, Zuyun Liu¹

Affiliations

¹ Center for Clinical Big Data and Analytics Second Affiliated Hospital, and Department of Big Data in Health Science School of Public Health, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Community Medicine and Health Care, Connecticut Convergence Institute for Translation in Regenerative Engineering, Institute for Systems Genomics, University of Connecticut Health, Farmington, Connecticut, USA.
³ Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA.
⁴ Department of Economics, Yale University, New Haven, Connecticut, USA.
⁵ Department of Family Medicine, Research Centre on Aging, CHUS Research Centre, University of Sherbrooke, Sherbrooke, Quebec, Canada.
⁶ Butler Columbia Aging Center and Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA.

PMID: 37789775
DOI: 10.1111/jgs.18611

Abstract

Background: With 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.

Methods: Data 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.

Results: The 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.

Conclusions: Accelerated 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.

Keywords: adverse health outcomes; biological age; lifestyles; mediation analysis; phenotypic age.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Aging
Cardiovascular Diseases*
Health Status Disparities
Humans
Life Style
Neoplasms* / complications
Nutrition Surveys
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding