Higher Serum Klotho Correlates with Lower Systemic Inflammation
Klotho is a longevity-associated protein. More of it extends life span in mice, and higher levels correlate with human health in later life. Klotho improves kidney function in older individuals, and improves cognitive function at any age, but it is far from clear as to which of the many aspects of cellular biochemistry and systemic function affected by klotho are most important in longevity, and how they interact. It may be the case that a reduced level of chronic inflammation is an important effect that helps to improve tissue function throughout the body, but it will take more than a single correlation study to make a compelling case for that to be true.
The alpha-Klotho gene is responsible for encoding a transmembrane protein that is predominantly found in renal tubules. This protein is known as alpha-Klotho and its extracellular domain can be shed to form a soluble variant known as S-Klotho. Studies have shown that S-Klotho has the ability to protect against a range of systemic diseases, such as chronic kidney disease, interstitial lung disease, and cardiovascular events. Furthermore, investigations have demonstrated that S-Klotho plays a pivotal role in modulating oxidative stress, apoptosis, cellular senescence, and endothelial function, positioning it as a promising target in the development of treatments for aging-related diseases. There is a growing body of evidence that suggests a relationship between S-Klotho levels and inflammation. Reduced levels of S-Klotho have been associated with a heightened risk of chronic inflammation, whereas increased levels of Klotho have been shown to possess anti-inflammatory effects.
The Systemic Immune-Inflammation Index (SII) is a measure obtained by dividing the product of neutrophil counts (N) and platelet counts (P) by lymphocyte counts (L). Compared with other inflammatory biomarkers, SII provides a more comprehensive evaluation of the systemic immune-inflammatory status by incorporating multiple components. The objective of this research is to determine the linkage between soluble Klotho (S-Klotho) level and systemic immune-inflammation index (SII).
Eligible participants with complete information of S-Klotho level and SII were selected from the National Health and Nutrition Examination Surveys (NHANES). Subsequently, weighted multivariate linear regression and subgroup analysis were carried out to evaluate the association. Totally, 11,108 adults with complete data on S-Klotho level, SII and other important covariates were included in final analysis. Multivariate liner regression revealed that high level of S-Klotho was associated with low level of SII after multivariate adjustments. When classifying S-Klotho into tertiles, participants in the highest tertile showed a decrease in SII level compared with those in the lowest tertile. The negative associations remained significant regardless of age and gender, and varied depending on smoking status and BMI subgroups.