The Circulating Level of Klotho Is Not Dependent upon Physical Fitness and Age-Associated Methylation Increases at the Promoter Region of the Klotho Gene

Abstract

(1) Background: Higher levels of physical fitness are believed to increase the physiological quality of life and impact the aging process with a wide range of adaptive mechanisms, including the regulation of the expression of the age-associated klotho (KL) gene and protein levels. (2) Methods: Here, we tested the relationship between the DNA methylation-based epigenetic biomarkers PhenoAge and GrimAge and methylation of the promoter region of the KL gene, the circulating level of KL, and the stage of physical fitness and grip force in two groups of volunteer subjects, trained (TRND) and sedentary (SED), aged between 37 and 85 years old. (3) Results: The circulating KL level is negatively associated with chronological age in the TRND group (r = −0.19; p = 0.0295) but not in the SED group (r = −0.065; p = 0.5925). The age-associated decrease in circulating KL is partly due to the increased methylation of the KL gene. In addition, higher plasma KL is significantly related to epigenetic age-deceleration in the TRND group, assessed by the biomarker of PhenoAge (r = −0.21; p = 0.0192). (4) Conclusions: The level of physical fitness, on the other hand, does not relate to circulating KL levels, nor to the rate of the methylation of the promoter region of the KL gene, only in males.

Higher levels of serum α-Klotho are longitudinally associated with less central obesity in girls experiencing weight gain

“…Another limitation is the lack of physical activity data in our subjects, as recent studies have described Klotho as an emerging exerkine ( 35 ) and as a factor with ergogenic potential, which can enhance physical performance ( 36 ). Klotho levels increase with exercise ( 9 , 37 ), regardless of the health condition of the individual ( 35 ) or the physical fitness ( 38 ) and this may explain, at least in part, the inverse association between physical fitness and cardiometabolic risk in school-age children ( 39 , 40 ).…”

The Longevity Protein Klotho: A Promising Tool to Monitor Lifestyle Improvements

“…Because the reported studies primarily measured α-klotho, only α-klotho will be discussed in this article and will be referred to as klotho. The transmembrane klotho isoform forms a complex with fibroblast growth factor receptor 23 (FGF23) [27]. It can be cleaved by cell-surface protease (sheddases), thus creating a soluble circulating klotho [20].…”

“…This soluble form acts as a hormone and is associated with longevity [27]. As reviewed by Arroyo et al, KL expression decreases with age in mice and in humans and is associated with a shorter lifespan [21].…”