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Research Paper|Volume 15, Issue 3|pp 765—776

Senolytic effect of high intensity interval exercise on human skeletal muscle

Wei-Horng Jean1, Yu-Wen Hsieh2, Li-Fan Lai2, Luthfia Dewi2, Yu-Chieh Liao2, Mengxin Ye2, Szu-Hsien Yu3, Chung-Lan Kao4, Chih-Yang Huang5,6,7, Chia-Hua Kuo1,8
  • 1Department of Anesthesiology, Far East Memorial Hospital, New Taipei City 220, Taiwan, ROC
  • 2Laboratory of Exercise Biochemistry, University of Taipei, Taipei City 11153, Taiwan, ROC
  • 3Department of Leisure Industry and Health Promotion, National Ilan University, Ilan, Taiwan, ROC
  • 4Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei City, Taiwan, ROC
  • 5Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROC
  • 6Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan, ROC
  • 7Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan, ROC
  • 8College of Physical Education, Chengdu University, Sichuan, China
* Equal contribution
Received: August 18, 2022Accepted: January 23, 2023Published: February 8, 2023
https://doi.org/10.18632/aging.204511

Copyright: © 2023 Jean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

p16INK4a expression is a robust biomarker of senescence for stem cells in human tissues. Here we examined the effect of exercise intensity on in vivo senescence in skeletal muscle, using a randomized counter-balanced crossover design. Biopsied vastus lateralis of 9 sedentary men (age 26.1 ± 2.5 y) were assessed before and after a single bout of moderate steady state exercise (SSE, 60% maximal aerobic power) and high intensity interval exercise (HIIE, 120% maximal aerobic power) on a cycloergometer accumulating same amount of cycling work (in kilojoule). Increases in cell infiltration (+1.2 folds), DNA strand break (+1.3 folds), and γ-H2AX+ myofibers (+1.1 folds) occurred immediately after HIIE and returned to baseline in 24 h (p < 0.05). Muscle p16Ink4a mRNA decreased 24 h after HIIE (−57%, p < 0.05). SSE had no effect on cell infiltration, p16Ink4a mRNA, and DNA strand break in muscle tissues. Senescence-lowering effect of HIIE was particularly prominent in the muscle with high pre-exercise p16INK4a expression, suggesting that exercise intensity determines the level of selection pressure to tissue stem cells at late senescent stage in human skeletal muscle. This evidence provides an explanation for the discrepancy between destructive nature of high intensity exercise and its anti-aging benefits.