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

Dora Aczel; Ferenc Torma; Matyas Jokai; Kristen McGreevy; Anita Boros; Yasuhiro Seki; Istvan Boldogh; Steve Horvath; Zsolt Radak

doi:10.3390/genes14020525

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

Genes (Basel). 2023 Feb 19;14(2):525. doi: 10.3390/genes14020525.

Authors

Dora Aczel¹, Ferenc Torma^{1

2}, Matyas Jokai¹, Kristen McGreevy³, Anita Boros¹, Yasuhiro Seki⁴, Istvan Boldogh⁵, Steve Horvath³, Zsolt Radak^{1

4}

Affiliations

¹ Research Institute of Sport Science, Hungarian University of Sport Science, 1123 Budapest, Hungary.
² Sports Neuroscience Division, Advanced Research Initiative for Human High Performance (ARIHHP), Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba 305-8574, Japan.
³ Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁴ Faculty of Sport Sciences, Waseda University, Tokorozawa 2-579-15, Japan.
⁵ Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.

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.

Keywords: aging; epigenetic clock; klotho; methylation; physical fitness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers / metabolism
DNA Methylation
Glucuronidase* / genetics
Humans
Male
Middle Aged
Physical Fitness
Promoter Regions, Genetic
Quality of Life*

Substances

Glucuronidase
Biomarkers

Grants and funding

ZR acknowledges support from the National Excellence Program (126823) and the Scientific Excellence Program, TKP2020-NKA-17, and TKP2021-EGA-37, at the Hungarian University of Sport Science, Ministry for Innovation and Technology, Hungary.