Association between biological aging and the risk of mortality in individuals with non-alcoholic fatty liver disease: A prospective cohort study

Haili Wang; Zhenqiu Liu; Hong Fan; Chengnan Guo; Xin Zhang; Yi Li; Xinyu Han; Tiejun Zhang

doi:10.1016/j.archger.2024.105477

Association between biological aging and the risk of mortality in individuals with non-alcoholic fatty liver disease: A prospective cohort study

Arch Gerontol Geriatr. 2024 May 7:124:105477. doi: 10.1016/j.archger.2024.105477. Online ahead of print.

Authors

Haili Wang¹, Zhenqiu Liu², Hong Fan¹, Chengnan Guo³, Xin Zhang¹, Yi Li¹, Xinyu Han¹, Tiejun Zhang⁴

Affiliations

¹ Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032, China.
² State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, 200438, China.
³ Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China.
⁴ Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China; Yiwu Research Institue, Fudan University, Yiwu, China. Electronic address: tjzhang@shmu.edu.cn.

PMID: 38735225
DOI: 10.1016/j.archger.2024.105477

Abstract

Background: The biological process of aging plays an important role in nonalcoholic fatty liver disease (NAFLD) development. However, epidemiological evidence about the association of biological aging with mortality risk among people with NAFLD is limited.

Methods: A total of 2199 participants with NAFLD from the National Health and Nutrition Examination Surveys (NHANES) III were included. The outcomes were all-cause and cause-specific (cardiovascular disease [CVD], cancer, and diabetes) mortality. We computed three BA measures, the Klemera-Doubal method (KDM) age, Phenotypic age, and homeostatic dysregulation (HD), by using 18 age-associated clinical biomarkers, and assessed their associations with mortality risk using Cox proportional hazards (CPH) models.

Results: After a median follow-up of 16 years, a total of 1077 deaths occurred. People with NAFLD who died during follow-up period exhibited higher baseline biological age (BA) and biological age accelerations (BAAs). The multivariate-adjusted CPH suggested that a one-standard deviation (SD) increase in KDM age acceleration, Phenotypic age acceleration, or HD was associated with a 3 %, 7 %, or 39 % elevated risk of all-cause mortality, respectively. The results of age-varying HRs showed that the associations of KDM age accelerations (AAs) and Phenotypic AAs with all-cause mortality appeared to be stronger in people with NAFLD younger than 45 years.

Conclusions: Biological aging was positively associated with both all-cause and cause-specific mortality among people with NAFLD, particularly among younger individuals.

Keywords: Biological aging; Mortality; NAFLD; NHANES.