Association Between Bilirubin and Klotho Levels in US Middleagedand Older Adults: NHANES 2007-2016

OBJECTIVE AND METHODS: Bilirubin, a potent endogenous antioxidant, protects against multiple diseases. This cross-sectional study explored the relationship between Serum Total Bilirubin (STB) and Serum Klotho (S-Klotho, an anti-aging biomarker) in 40-79-year-olds from the 2007-2016 NHANES survey. Statistical analysis used a multivariable regression model; a Restricted Cubic Spline (RCS) model evaluated potential non-linear STB-S-Klotho associations. Subgroup analyses and sensitivity tests ensured the robustness. RESULTS: The analysis included 4,562 individuals aged 40-79. Both unadjusted and adjusted models showed a significant positive association between STB and S-Klotho (β = 2.84, P = 0.02 in the weighted, fully adjusted model). The RCS curve indicated no significant non-linearity (P for non-linearity = 0.211). Subgroup analyses revealed stronger associations in females, normal-weight individuals, and those without diabetes mellitus (DM) or hypertension. DISCUSSION: This is the first study exploring the STB-S-Klotho relationship. While human studies on bilirubin's role in aging have inconsistent conclusions, animal and mechanistic research show that elevated bilirubin reduces oxidative stress and inflammation, potentially protecting against age-related conditions. CONCLUSION: Our findings confirm a positive STB-S-Klotho correlation in middle-aged and older adults, suggesting bilirubin may be a potential S-Klotho biomarker and reflect biological aging processes.