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 (beta=0.04, 95 CI%: 0.00, 0.07, P=0.024) and female (beta=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 (beta=0.23, 95 CI%: 0.14, 0.32, P<0.001). However, the association between total bilirubin concentration and telomere length was not significant (beta=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.

Automated summary

This cross-sectional study using NHANES data found a positive and nonlinear association between total bilirubin concentration and telomere length. Higher total bilirubin concentration was associated with longer telomere length in both males and females. An inverted U-shaped relationship between total bilirubin and telomere length was observed as well.