Senolytic effects of exercise in human muscles require acute inflammation

• Published in: Aging (Albany, NY.) Vol. 16; no. 10; pp. 8599 - 8610
• Main Authors: Jean, Wei-Horng, Lin, Yin-Chou, Ang, Pei-Yao, Goto, Kazushige, Lin, Chao-An, Dewi, Luthfia, Liao, Yu-Chieh, Huang, Chih-Yang, Kuo, Chia-Hua
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 15.05.2024
• Subjects: Adult; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; CD11b Antigen - genetics; CD11b Antigen - metabolism; Cross-Over Studies; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Exercise - physiology; High-Intensity Interval Training; Humans; Ibuprofen - pharmacology; Inflammation - metabolism; Male; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Research Paper; RNA, Messenger - metabolism; Young Adult; cellular senescence; high-intensity intermittent exercise; inflammation; p16INK4a; NSAID
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.205827

Higher intensity exercise, despite causing more tissue damage, improved aging conditions. We previously observed decreased p16 mRNA in human skeletal muscle after high-intensity interval exercise (HIIE), with no change following equivalent work in moderate-intensity continuous exercise. This raises the question of whether the observed senolytic effect of exercise is mediated by inflammation, an immune response induced by muscle damage. In this study, inflammation was blocked using a multiple dose of ibuprofen (total dose: 1200 mg), a commonly consumed nonsteroidal anti-inflammatory drug (NSAID), in a placebo-controlled, counterbalanced crossover trial. Twelve men aged 20-26 consumed ibuprofen or placebo before and after HIIE at 120% maximum aerobic power. Multiple muscle biopsies were taken for tissue analysis before and after HIIE. p16 cells were located surrounding myofibers in muscle tissues. The maximum decrease in p16 mRNA levels within muscle tissues occurred at 3 h post-exercise (-82%, < 0.01), gradually recovering over the next 3-24 h. A concurrent reduction pattern in CD11b mRNA (-87%, < 0.01) was also found within the same time frame. Ibuprofen treatment attenuated the post-exercise reduction in both p16 mRNA and CD11b mRNA. The strong correlation (r = 0.88, < 0.01) between p16 mRNA and CD11b mRNA in muscle tissues suggests a connection between the markers of tissue aging and pro-inflammatory myeloid differentiation. In conclusion, our results suggest that the senolytic effect of high-intensity exercise on human skeletal muscle is mediated by acute inflammation.