Association of Serum Total Bilirubin Concentration with Telomere Length: The National Health and Nutrition Examination Survey

INTRODUCTION: Mildly increased bilirubin concentration has a protective effect on oxidative stress–related diseases. However, it remains unknown whether elevated circulating bilirubin is associated with longer telomere length. The aim of this cross-sectional study was to examine the association between total bilirubin concentration and telomere length. METHODS: We used the data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The multivariable linear regression model was used to examine the association between total bilirubin concentration and telomere length. The nonlinear relationship was analyzed using a generalized additive model with the smoothing plot. RESULTS: A total of 7818 participants with a mean age of 49.20 ± 18.82 years were included. Compared with the lowest concentration of total bilirubin (Q1), the highest quartile of total bilirubin concentration was associated with longer telomere length in male (β = 0.04, 95 CI%: 0.00, 0.07, P = 0.024) and female (β = 0.04, 95 CI%: 0.02, 0.04, P = 0.002). Furthermore, an inverted U-shaped relationship between total bilirubin and telomere length was found. On the left of turning points (total bilirubin < 0.5 mg/dL), total bilirubin concentration was positively associated with telomere length (β = 0.23, 95 CI%: 0.14, 0.32, P < 0.001). However, the association between total bilirubin concentration and telomere length was not significant (β = 0.01, 95% CI: -0.01, 0.04, P = 0.346) above the turning point. CONCLUSION: This is the first evidence based on a nationally representative survey demonstrating a positive and nonlinear association between total bilirubin concentration and telomere length. Future large-scale prospective studies are warranted to confirm our findings.