Uric acid mediates the association between testosterone and α-Klotho among males: results from the NHANES 2013-2016.

Purpose: This study initially conducted a cross-sectional analysis to examine the association between total testosterone (TT), uric acid, and Klotho. The investigation examined whether uric acid mediates the association between TT and Klotho in males.

Methods: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016, this study performed weighted multivariable-adjusted linear regression to evaluate the association between TT, uric acid, and α-Klotho. Then, mediation analysis was conducted to delineate the potential mediating role of uric acid in the TT-Klotho association.

Results: Multivariable linear regression analyses revealed inverse relationships between TT and uric acid (β = - 2.75, 95% CI: - 4.21, 1.28, p < 0.001) and between uric acid and α-Klotho (β = - 4.80, 95% CI: - 6.47, - 3.13, p < 0.001). Conversely, a positive correlation existed between TT and α-Klotho (β = 5.38, 95% CI: 2.23, 8.53, p < 0.001). Updated subgroup analyses show that the association strength between α-Klotho, TT, and uric acid levels was consistent across various population settings without significant variations. Restricted cubic spline analysis identified a non-linear association between TT and uric acid with an inflection point at 201 ng/mL. Mediation analysis confirmed uric acid-mediated 18.59% of the association between TT and α-Klotho (p < 0.001), highlighting its significant intermediary role.

Conclusion: This study elucidates the complex interrelationship between TT, uric acid, and α-Klotho, highlighting uric acid's significant mediating role. These findings provide novel insights into the hormonal and metabolic mechanisms underlying age-related processes and longevity.