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

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.

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.

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.

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.