Research Paper Volume 16, Issue 10 pp 8599—8610
Senolytic effects of exercise in human muscles require acute inflammation
- 1 Department of Anesthesiology, Far East Memorial Hospital, New Taipei City 220, Taiwan
- 2 Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Taoyuan 33378, Taiwan
- 3 Laboratory of Exercise Biochemistry, University of Taipei, New Taipei City 11153, Taiwan
- 4 Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu 525-8577, Japan
- 5 Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
- 6 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
- 7 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
- 8 Department of Health Management and Enhancement, Open University of Kaohsiung, Kaohsiung 812, Taiwan
Received: October 30, 2023 Accepted: February 8, 2024 Published: May 15, 2024
https://doi.org/10.18632/aging.205827How to Cite
Copyright: © 2024 Jean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Higher intensity exercise, despite causing more tissue damage, improved aging conditions. We previously observed decreased p16INK4a 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. p16INK4a+ cells were located surrounding myofibers in muscle tissues. The maximum decrease in p16INK4a mRNA levels within muscle tissues occurred at 3 h post-exercise (−82%, p < 0.01), gradually recovering over the next 3–24 h. A concurrent reduction pattern in CD11b mRNA (−87%, p < 0.01) was also found within the same time frame. Ibuprofen treatment attenuated the post-exercise reduction in both p16INK4a mRNA and CD11b mRNA. The strong correlation (r = 0.88, p < 0.01) between p16INK4a 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.