High-intensity physical exercise increases serum α-klotho levels in healthy volunteers

The recently discovered klotho proteins have roles in a diverse range of metabolic processes with the oldest protein, α-klotho, implicated in various cellular pathways in energy, glucose, and phosphate metabolism. Circulating soluble klotho (sKl), derived from membrane α-klotho cleavage, not only has effects on ion channels and insulin signaling pathways, but is inversely associated with mortality. Effects of physical exercise on sKl have not been well studied. The effect of a single high-intensity standardized exercise on sKl and serum phosphate (sPi) levels in healthy adults was investigated. A standard Bruce protocol treadmill exercise was undertaken by 10 fasting healthy volunteers. sKl, sPi, and blood glucose levels were measured in samples collected 1-week prior, immediately pre (T_pre), 0 (T_post), 30 (T₃₀), 240 (T₂₄₀) min, and 1-week after exercise. Median (interquartile range) age of participants was 47.5 (44-51) years; five (50%) were male. All study participants achieved at least 90% predicted maximum heart rate (MHR). sKl increased acutely after exercise (T_pre median 448 pg/mL vs. T_post median 576 pg/mL; p < 0.01). There was a nonsignificant sPi decline at T₃₀ (T_pre 0.94 ± 0.12 mmol/L vs. T₃₀ 0.83 ± 0.22 mmol/L). Exercise led to a reduction in blood glucose by T₂₄₀ with median glucose levels at T_pre, T_post, T₃₀, and T₂₄₀ of 6.0, 6.5, 6.3, and 5.7 mmol/L, respectively. In conclusion, a single high-intensity exercise session is associated with a transient increase in sKl, a delayed reduction in blood glucose, and a nonsignificant decrease in sPi levels in healthy adults. The evaluation of long-term effects of cardiovascular fitness programs on sKl and sPi in healthy individuals and disease cohorts are required to identify potential lifestyle modifications to help improve chronic disease management and long-term outcomes.