Introduction: Physical exercise improves cardiovascular health through pleiotropic mechanisms. One central mechanism is the exercise-induced release of exerkines. They act as molecular messengers, facilitating communication between different bodily systems via endocrine (bloodstream), paracrine (to nearby cells), and autocrine (on the originating cell) pathways. One such exerkine that has gained growing attention in the past few years is the anti-aging protein klotho.
Methods: In this study, we investigated the effects of an acute, high-intensity exercise intervention (cardiopulmonary exercise test on a bicycle ergometer until exhaustion) on klotho levels in young (n=20, age 27.5 ± 3.6 years, 10 female) and older adults (n=19, age 70.2 ± 2.7 years, 10 female). Additionally, we investigated the potential modulating effects of a single dose of the SGLT-2 inhibitor empagliflozin (10 mg) on klotho release given 24 hours before exercise in the older adult group. Blood samples were collected before, immediate after, and 24 hours after exercise.
Results: Statistical analysis revealed that older adults (865.0 pg/ml ± 593.6 pg/ml) had lower klotho levels than young adults (1315.9 pg/ml ± 828.95 pg/ml, p=.041). In both groups, exercise resulted in an acute (immediate after exercise, p<0.001) and persistent (24 h following exercise, p<0.001) increase of klotho levels. The klotho release dynamics were not influenced by inhibition of SGLT-2.
Discussion: Our findings show that high intensity exercise is associated with increased klotho levels in both, young and older adults, particularly in individuals with higher cardiovascular fitness. Future research is needed to investigate the clinical relevance of exercise-associated klotho release for the beneficial effects of exercise on cardiovascular health.
