Serum klotho levels modify the positive relationship of depression and all-cause mortality risk

Sci Rep. 2025 Sep 18;15(1):32592. doi: 10.1038/s41598-025-04948-8.

ABSTRACT

The role of klotho on the association of depression and mortality has not been studies comprehensively. This study aims to examine this relationship in US adults. Data of 12,656 participants in the National Health and Nutrition Examination Surveys (NHANES) 2007-2016 was collected, of which 1265 participants (10.0%) with depression. Weighted Cox proportional hazards models were applied to detect the combined effects of klotho and depression on all-cause mortality risk. During the follow-up (Median 91.0 months), 1423 (11.2%) participants died. Klotho was nonlinearly associated with all-cause mortality risk (P _nonlinear: <0.001). When participants with high klotho level (≥ 902.33 pg/mL), depression did not increase all-cause mortality risk (HR: 0.94; 95% CI 0.58, 1.52; P: 0.802); when participants with low klotho level (< 902.33 pg/mL), depression increased all-cause mortality risk (HR: 1.59; 95% CI 1.23, 2.07; P: <0.001). A significant interaction was detected between depression and klotho on all-cause mortality risk (P _interaction = 0.040). Depression-associated mortality risk is only found in the low klotho group. Klotho can modify the positive relationship of depression and mortality. Serum klotho levels is a reliable predictor of prognosis and may be a promising therapeutic target to decrease mortality risk for individuals with depression.

PMID:40968120 | DOI:10.1038/s41598-025-04948-8