Aging
Physiologic Aging and Longevity: The Association of 6 Blood Biomarkers with Age at Death in the Cardiovascular Health Study Lauren Q. Vuong* Lauren Vuong Vuong Vuong Vuong Vuong Vuong Vuong Department of Epidemiology & Population Health, Stanford University
Ageing is accompanied by dysfunction in inflammation, kidney and cardiovascular function, and metabolism, which can lead to earlier mortality. Prior studies have observed relationships between biomarkers reflecting these pathways and health outcomes, but few have evaluated longevity. Among participants of the Cardiovascular Health Study (CHS), who were followed from enrollment in 1989 through death, we examined the association between 6 blood biomarkers—high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cystatin C, B-type natriuretic peptide (BNP), insulin-like growth factor 1 (IGF-1), dehydroepiandrosterone sulfate (DHEAS)—and age at death.
This study included 5,795 Black and White participants from 4 sites in the U.S.: Pittsburgh, PA, Sacramento County, CA, Washington County, MD, and Forsyth County, MD. We used linear regressions of log-base-2 biomarkers taken near age 70 on age at death and adjusted for race, education, smoking, physical activity, body mass index (BMI), blood pressure, and estimated glomerular filtration rate (eGFR). In hs-CRP models, we stratified by sex to account for significant interaction, and a quadratic term was included for DHEAS and IGF-1 models to account for U-shaped relationships.
The median (IQR) age at biomarker measurement was 72.9 (70.0 – 77.0) years, and the median (IQR) age at death was 88.5 (83.0 – 93.1) years in females and 86.2 (80.8 – 91.0) in males. Unadjusted associations are shown in Figure 1. After adjusting for covariates, a 2-fold higher level of IL-6, cystatin C, and BNP was associated with significant 1.01-, 3.99-, and 1.02-year reductions in longevity (95% CIs: 0.80–1.22; 3.47–4.50; 0.75–0.99). A 2-fold higher level of hs-CRP was associated with a significant 0.30-year reduction longevity (95% CI: 0.14-0.46) among females and a significant 0.46-year reduction (95% CI: 0.29-0.64) among males. For DHEAS and IGF-1, significant U-shaped relationships between these biomarkers and age at death were observed, as indicated by p < 0.001 for coefficients of the quadratic terms in these models.
Higher levels of cystatin C, a biomarker reflecting worse kidney function, were most strongly associated with earlier death. Our results are consistent with prior literature and illustrate how these biomarkers relate to longevity outcomes.
