The relationship between serum α-Klotho with all-cause and cause-specific mortality

Area of Science:

• Biochemistry
• Gerontology
• Epidemiology

Background:

• The association between alpha-Klotho (αK) and mortality remains debated, lacking investigation in large, diverse populations.
• Serum αK protein levels are a potential biomarker, but their prognostic value for mortality requires further clarification.

Purpose of the Study:

• To examine the relationship between serum αK protein levels and all-cause and cause-specific mortality.
• To investigate this association in a cohort representative of the US population using a large dataset.

Main Methods:

• Utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007-2016.
• Employed Cox proportional hazard and competing risk models to analyze nonlinear associations between αK levels (as a quadratic variable) and mortality.
• Adjusted for numerous covariates including age, BMI, diabetes, smoking, and estimated glomerular filtration rate.

Main Results:

• A U-shaped relationship was observed between serum αK levels and all-cause mortality in multivariable-adjusted models.
• This U-shaped association was also noted for cancer mortality, with both low and high αK levels correlating with increased risk.
• No significant relationship was found between αK levels and cardiovascular or other causes of mortality.

Conclusions:

• A significant U-shaped association exists between serum αK levels and both all-cause and cancer mortality in a large, diverse US population.
• Further research is warranted to elucidate the biological mechanisms underlying these observed relationships.