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.