Objectives: To determine the association between physical activity and physical fitness levels (i.e. cardiorespiratory fitness and muscular strength) and the shed form of the alpha-Klotho gene (S-Klotho plasma levels) in middle-aged sedentary adults. Study design and main outcome measures: A total of 74 middle-aged sedentary adults (52.7% women; 53.7 +/- 5.1 years old) were enrolled in the FIT-AGEING study. Physical activity and sedentary time were assessed with a wrist-worn accelerometer. Maximal oxygen uptake (VO(2)max) was determined by a maximum treadmill test using indirect calorimetry. Lower- and upper-body muscular strength were assessed by an isokinetic strength test and by the hand grip strength test, respectively. The S-Klotho plasma levels were measured in the EDTA plasma using a solid-phase sandwich enzyme-linked immunosorbent assay. Results: Based on the principal-component analysis, overall physical activity, moderate and vigorous physical activity levels, and sedentary time (as outcomes included in the ‘sedentary time and physical activity’ category) explained a total of 17.5% of the cumulative variance in S-Klotho plasma levels, while extension peak torque, hand grip strength, and maximal oxygen uptake (as outcomes included in the ‘physical fitness’ category) explained a total of 15.5% of the cumulative variance in S-Klotho plasma levels. Based on the loading of variables in these 2 categories, the percentage of the cumulative variance in S-Klotho plasma level explained was 28.9%s; this reached 33.0% of cumulative variance when sex was included in the model. Conclusions: In summary, our results indicate that physical activity and physical fitness levels are associated with S-Klotho plasma levels in middle-aged sedentary adults. Therefore, the S-Klotho protein could be a key factor in the relationship between physical activity and physical fitness and health improvements during the ageing process.
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