Association of Blood Chemistry Quantifications of Biological Aging With Disability and Mortality in Older Adults

Abstract

Quantification of biological aging has been proposed for population surveillance of age-related decline in system integrity and evaluation of geroprotective therapies. However, methods of quantifying biological aging have been little studied in geriatric populations. We analyzed three clinical-biomarker-algorithm methods to quantify biological aging. Klemera-Doubal method Biological Age and homeostatic dysregulation algorithms were parameterized from analysis of U.S. National Health and Nutrition Examination Surveys (NHANES) data (N = 36,207) based on published methods. Levine method Biological Age was adapted from published analysis of NHANES data. Algorithms were applied to biomarker data from the Duke Established Populations for Epidemiologic Studies of the Elderly (Duke-EPESE) cohort of older adults (N = 1,374, aged 71-102 years, 35% male, 52% African American). We tested associations of biological aging measures with participant reported Activities of daily living (ADL), instrumental activities of daily living (IADL) dependencies, and mortality. We evaluated the sensitivity of results to the demographic composition of reference samples and biomarker sets used to develop biological aging algorithms. African American and white Duke-EPESE participants with more advanced biological aging reported dependence in more ADLs and IADLs and were at increased risk of death over follow-up through 2017. Effect sizes were similar across algorithms, but were strongest for Levine method Biological Age (per-quintile increase in ADL incidence rate ratio = 1.25, 95% confidence interval [1.17-1.37], IADL incidence rate ratio = 1.23 [1.15-1.32], mortality hazard ratio = 1.12 [1.08-1.16]). Results were insensitive to demographic composition of reference samples, but modestly sensitive to the biomarker sets used to develop biological aging algorithms. Blood-chemistry-based quantifications of biological aging show promise for evaluating the effectiveness of interventions to extend healthy life span in older adults.

Keywords: Age-related pathology; Bioinformatics; Human aging; Mortality.