Relationship between aerobic fitness, antioxidant capacity and the anti-aging hormone, Klotho

BACKGROUND: It is well established that aerobic exercise training increases the expression of antioxidant enzymes. This results from exercise-induced oxidative stress which provides a stimulus to increase antioxidant capacity. Therefore, aerobic exercise training protects against oxidative damage by improving the body’s ability to maintain the balance between reactive oxygen species and antioxidants. The soluble form of the protein Klotho (s-Klotho) was previously shown to increase resistance to oxidative damage in mutant mice by activation of FoxO forkhead transcription factors (FOXO) and subsequent expression of manganese superoxide dismutase (MnSOD). Recent findings showed that s-Klotho concentrations also increased in response to acute and chronic aerobic exercise in both human and animal models. This led to the hypothesis that increases in s-Klotho may be a mechanism by which aerobic training improves antioxidant capacity. METHODS: Partial and zero-order correlations were used to investigate the relationship between aerobic fitness (measured by maximal oxygen consumption [VO_2max]), total antioxidant capacity (TAC) and s-Klotho concentrations in serum and plasma, respectively, in ten physically-active volunteers. RESULTS: When sex was controlled for, a significant positive correlation was observed between VO_2max and TAC (r=0.723, P=0.028). s-Klotho concentrations and TAC were also significantly correlated (r=0.664, P=0.036). CONCLUSIONS: These findings suggest that antioxidant capacity is positively related to both aerobic fitness and s-Klotho concentrations. The latter is a novel finding and supports the notion that s-Klotho works as a pro-antioxidant hormone. Considering previous findings showing an increase in s-Klotho concentrations following aerobic training, exercise-induced increases in Klotho expression or secretion may augment the production of antioxidant enzymes.