The joint effects of frailty and telomere length for predicting mortality in older adults: the National Health and Nutrition Examination Survey 1999–2002

Background: Frailty and short telomere length, which address different aspects of biological aging, are separately associated with mortality in older adults. Aims: To evaluate whether the combination of these two biomarkers would be a better predictor of mortality than either alone. Methods: This present study included participants 60 years of age or older from the National Health and Nutrition Examination Survey in the 1999–2002 phase. The frailty phenotype was identified based on the Fried definition. Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative polymerase chain reaction (PCR). Cox proportional hazards regression models were used to estimate the individual and combined effects of frailty phenotype and telomere length on all-cause and cardiovascular mortality. Results: Compared with participants with neither impairment, the mortality risks increased slightly among participants with short telomere length only (hazard ratio [HR] 1.19, 95% confidence interval [CI]: 1.00–1.42) or pre-frailty only (HR 2.16, 95% CI 1.80–2.60) and gradually elevated approximately 3 folds with both short telomere length and pre-frailty (HR 2.23, 95% CI 1.81–2.74) or frailty (HR 3.57, 95% CI 2.56–4.98). Moreover, participants with both short telomere length and frailty had the highest increased all-cause mortality (HR 5.16, 95% CI 3.38–7.85) and cardiovascular mortality (HR 4.67, 95% CI 2.02–10.82). Discussion and conclusions: The combined predictor had more capability of predicting mortality, which suggested that integrating both molecular biomarkers and physiological functional parameters would be a more informative measure of biological aging.