Abstract P017: Biomarkers Representing Aging-Related Biological Pathways Are Associated With All-Cause Mortality: The Framingham Study

Abstract

Background: Chronological aging is the result of different biological processes and molecular mechanisms that, if identified, may increase our ability to mitigate aging-related decline in body functions. We hypothesized that aging-related biomarkers reflecting multiple biological pathways are associated with all-cause mortality. Methods and Results: We related leukocyte telomere length (LTL) expressed by terminal restriction fragment (TRF) length, urinary concentrations of creatinine-corrected isoprostanes, circulating concentrations of insulin-like growth factor (IGF)-1, and asymmetrical dimethylarginine (ADMA) in up to 2314 Framingham Offspring Study participants attending routine examination cycles (mean age 58 yrs, 55% women) to all-cause mortality using Cox proportional hazards regression models. Biomarkers were modeled individually and in combination, adjusting for age, sex, body mass index, systolic blood pressure, diabetes, smoking status, hypertension medication, total cholesterol/HDL. We created also a biomarker score as a composite of biomarkers associated with mortality risk. Kaplan Meier curves were created ( Figure ) to graphically present the survival time as a function of tertiles of the biomarker score. There were 593 deaths (274 women) during a median follow-up of 20 years. TRF and IGF-1 values were inversely related to all-cause mortality (multivariable-adjusted hazard ratios [HR] per SD increase, 0.86, 95% confidence interval [CI], 0.75-0.998 and 0.89, 95% CI 0.81-0.97 for TRF and IGF-1, respectively). Isoprostanes and ADMA values were positively related to all-cause mortality (multivariable-adjusted HR per SD increase, 1.17, 95% CI, 1.11-1.23, and 1.09, 95% CI, 1.01-1.18, respectively). Conclusion: In our prospective community-based study, aging-related biomarkers were associated with all-cause mortality, supporting the concept that molecular pathways represented by these biomarkers may reflect the processing of aging in the community.