Ibuprofen attenuates senolytic effects of exercise in human skeletal muscle

Abstract Muscle regeneration after injury requires inflammation. In this study, we examine the role of inflammation on the exercise-induced senolytic effect in human skeletal muscle by ibuprofen treatment using a placebo-controlled counterbalanced crossover trial. Twelve men aged 20-26 consumed ibuprofen (total dose: 1200 mg) or placebo before and after high-intensity interval exercise (HIIE) at 120% maximum aerobic power (total work ~ 70 kJ). Multiple muscle biopsies were taken for tissue analysis before and after HIIE. p16 INK4a+ cells were located surrounding myofibers in human muscle. We found a quick decreased p16 INK4a mRNA levels (-82%, p = 0.01, d = 1.23) of p16 INK4a+ cells in muscle tissues at 3 hours post-exercise and persisting to 24 hours. Ibuprofen delayed this senolytic effects of HIIE in muscle tissues. A strong correlation between p16 INK4a mRNA and CD11b mRNA in muscle tissues (r = 0.88, p < 0.001) suggests a possibility that the senolytic effect of exercise lowered pro-inflammatory myeloid differentiation in human muscles. The result of the study suggests the role of inflammation in the senolytic effect of high intensity exercise in human skeletal muscle. This transient proinflammatory stimulus results in lowered basal inflammation persisting over an extended period.