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Peer-reviewedCC BY 4.0Journal of Clinical Medicine

Acute Effects of Exhaustive Exercise on the Anti-Aging Protein S-Klotho in Young Females and Males with Obesity

4 affiliations
  1. 1Department of Community Medicine and Rehabilitation, Section of Sports Medicine, and Umeå School of Sport Sciences, Umeå University, 901 87 Umeå, Sweden
  2. 2Själevad Health Care Center, Sjukhemsvägen 2 B, 894 30 Örnsköldsvik, Sweden
  3. 3Department of Medical Sciences, Clinical Chemistry, Uppsala University, 751 85 Uppsala, Sweden
  4. 4Department of Medical and Translational Biology, Umeå University, 901 87 Umeå, Sweden

Abstract

Background: Circulating S-Klotho is increasingly recognized as an anti-aging protein linked to cardiovascular protection and metabolic regulation. Although exercise elevates S-Klotho, the dose–response threshold and metabolic determinants of this response in young adults with obesity, a population at heightened risk for cardiometabolic dysfunction, remain poorly characterized. To examine the acute effects of submaximal and maximal cycling on circulating S-Klotho in young adults with obesity and to identify key metabolic predictors of exercise-induced changes. Methods: Eighteen young (26 ± 3 years, BMI 30 ± 2 kg/m2) males and females completed incremental cycling to exhaustion. Serum S-Klotho was assessed at rest, after submaximal (SubMax), and post-maximal (Max) exercise. Covariates included cardiorespiratory fitness (VO2max), iDXA body composition, HOMA-IR, and hsCRP. Predictor Screening and Partial Least Squares (PLS) regression with fivefold cross-validation were used to identify determinants of exercise-induced S-Klotho responses. Results: A significant acute increase in S-Klotho was observed (Main Effect of Time: F(2,32) = 9.4, p = 0.0006). Post hoc analysis revealed an intensity-dependent threshold, with a significant surge occurring only between submaximal and maximal exertion (p = 0.021; Rest to Max: p = 0.0005). No significant sex differences or interactions were observed (p > 0.05). The PLS model explained 74% of the variance in S-Klotho changes, identifying systemic inflammation (Log10[hsCRP]) and visceral adiposity as the primary predictive factors. Conclusions: Exhaustive exercise acutely increases circulating S-Klotho in young adults with obesity, independent of sex. This response is intensity-dependent and primarily driven by baseline metabolic risk factors. S-Klotho may represent an acute exercise-responsive biomarker linked to metabolic health in at-risk populations. These exploratory findings warrant confirmation in larger and adequately powered studies.

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BibTeX
@article{svensson2026acute,
  title = {{Acute Effects of Exhaustive Exercise on the Anti-Aging Protein S-Klotho in Young Females and Males with Obesity}},
  author = {Michael Svensson and Lisa Blomqvist and Torbjörn Åkerfeldt and Pär Steneberg and Christer Malm},
  journal = {Journal of Clinical Medicine},
  year = {2026},
  month = oct,
  doi = {10.3390/jcm15218313},
  url = {https://www.mdpi.com/2077-0383/15/21/8313},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Acute Effects of Exhaustive Exercise on the Anti-Aging Protein S-Klotho in Young Females and Males with Obesity
AU  - Michael Svensson
AU  - Lisa Blomqvist
AU  - Torbjörn Åkerfeldt
AU  - Pär Steneberg
AU  - Christer Malm
PY  - 2026
DA  - 2026/10/26
JO  - Journal of Clinical Medicine
DO  - 10.3390/jcm15218313
UR  - https://www.mdpi.com/2077-0383/15/21/8313
AB  - Background: Circulating S-Klotho is increasingly recognized as an anti-aging protein linked to cardiovascular protection and metabolic regulation. Although exercise elevates S-Klotho, the dose–response threshold and metabolic determinants of this response in young adults with obesity, a population at heightened risk for cardiometabolic dysfunction, remain poorly characterized. To examine the acute effects of submaximal and maximal cycling on circulating S-Klotho in young adults with obesity and to identify key metabolic predictors of exercise-induced changes. Methods: Eighteen young (26 ± 3 years, BMI 30 ± 2 kg/m2) males and females completed incremental cycling to exhaustion. Serum S-Klotho was assessed at rest, after submaximal (SubMax), and post-maximal (Max) exercise. Covariates included cardiorespiratory fitness (VO2max), iDXA body composition, HOMA-IR, and hsCRP. Predictor Screening and Partial Least Squares (PLS) regression with fivefold cross-validation were used to identify determinants of exercise-induced S-Klotho responses. Results: A significant acute increase in S-Klotho was observed (Main Effect of Time: F(2,32) = 9.4, p = 0.0006). Post hoc analysis revealed an intensity-dependent threshold, with a significant surge occurring only between submaximal and maximal exertion (p = 0.021; Rest to Max: p = 0.0005). No significant sex differences or interactions were observed (p > 0.05). The PLS model explained 74% of the variance in S-Klotho changes, identifying systemic inflammation (Log10[hsCRP]) and visceral adiposity as the primary predictive factors. Conclusions: Exhaustive exercise acutely increases circulating S-Klotho in young adults with obesity, independent of sex. This response is intensity-dependent and primarily driven by baseline metabolic risk factors. S-Klotho may represent an acute exercise-responsive biomarker linked to metabolic health in at-risk populations. These exploratory findings warrant confirmation in larger and adequately powered studies.
SN  - 2077-0383
ER  -