Research AppraisalSystematic Review

Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis

Journal of physiology and biochemistryde Oliveira, Túlio Medina Dutra, Felício, Diogo Carvalho, da Silva Ribeiro, Taynara et al.2 May 2026DOI

Clinical Snapshot

75CEBM
Evidence: ModerateSystematic Review

PICO Framework

P — PopulationHealthy individuals and patients with chronic diseases, aged 18-85 years (n=2,765)
I — InterventionAerobic, resistance, or combined exercise interventions classified as acute (single session), subacute (<12 weeks), or chronic (≥12 weeks)
C — ComparatorControl groups or baseline measurements
O — OutcomesPlasma s-Klotho levels measured as standardised mean difference

Bottom Line

This meta-analysis of 41 studies (2,765 participants) demonstrates that exercise interventions consistently increase plasma s-Klotho levels, a biomarker associated with healthy aging and longevity. Acute and subacute aerobic exercise showed moderate benefits in both healthy individuals and those with chronic diseases, while chronic resistance training (≥12 weeks) produced the largest effects, particularly in diseased populations. However, the clinical significance remains uncertain due to high risk of bias in most included studies and evidence quality ranging from very low to moderate. While these findings support the biological plausibility of exercise's anti-aging effects through s-Klotho pathways, clinicians should interpret results cautiously. The evidence supports existing recommendations for regular exercise in healthy aging, but routine s-Klotho monitoring is not yet justified for clinical practice. Further high-quality randomised controlled trials are needed to establish clinical utility and optimal exercise prescriptions.

Evidence: Moderate

Key Findings

  • P Value: Not reported in abstract

  • Effect Size: Acute/subacute aerobic: SMD 0.69 (healthy), 0.62 (diseased); Chronic exercise: SMD 0.57 (healthy), 1.51 (diseased)

  • Primary Outcome: Plasma s-Klotho levels measured as standardised mean difference

  • Nnt Or Sensitivity: Resistance exercise thrice weekly showed highest effect (SMD 1.60; 95%CI 0.81-2.38)

  • Confidence Interval: Healthy acute/subacute: 95%CI 0.41-0.97; Diseased chronic: 95%CI 0.87-2.16

Clinical Application

Exercise interventions are generally feasible and accessible, though optimal protocols require further research Relevant to Australian practice given aging population and chronic disease burden. Aligns with RACGP guidelines promoting physical activity for healthy aging, though s-Klotho testing not routinely available through PBS Adults aged 18-85 years, both healthy individuals and those with chronic diseases

Abstract

Exercise exerts beneficial effects on multiple physiological systems, influencing biomarkers associated with aging processes and chronic diseases. This systematic review and meta-analysis aimed to evaluate the acute, subacute, and chronic effects of exercise on s-Klotho levels in healthy individuals and patients with chronic diseases. A comprehensive search was conducted in electronic databases. Included studies were randomized and non-randomized studies assessing the effects of aerobic, resistance, or combined exercise on s-Klotho levels. Interventions were classified as acute (single session), subacute (< 12 weeks), or chronic (≥ 12 weeks). Risk of bias was assessed using RoB 2 and ROBINS-I tools, and quality of evidence was evaluated with the GRADE framework. Forty-one studies were included in the qualitative synthesis, and 30 in the meta-analysis, comprising 2,765 participants (18-85 years). Twenty-five involved healthy individuals, while 21 included patients with chronic diseases. Acute and subacute aerobic exercise increased s-Klotho levels in healthy individuals (SMD 0.69; 95%CI 0.41-0.97) and diseased populations (SMD 0.62; 95%CI 0.11-1.12). Chronic exercise (12-36 weeks) showed significant increases in healthy (SMD 0.57; 95%CI 0.33-0.82) and diseased populations (SMD 1.51; 95%CI 0.87-2.16). Resistance exercise thrice weekly demonstrated the highest effect (SMD 1.60; 95%CI 0.81-2.38). Most studies had high risk of bias, with quality of evidence ranging from very low to moderate. Exercise significantly increases s-Klotho levels, with acute and subacute aerobic sessions benefiting healthy and diseased populations, while chronic resistance exercise elicited greater responses in diseased populations. Despite promising findings, low methodological quality suggests cautious interpretation.

References

  1. 1.de Oliveira, T. M. D., Felício, D. C., da Silva Ribeiro, T., Filho, J. E., Amaro-Gahete, F. J., Costa, G. B., Nascimento, J. W. L., de Moura Reboredo, M., & Malaguti, C. (2026). Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis. Journal of Physiology and Biochemistry. https://doi.org/10.1080/0886022x.2023.2252093
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