Middle East J Rehabil Health Stud. 2022 April; 9(2):e121818. Published online 2022 April 6. doi: 10.5812/mejrh.121818. Research Article Short and Long-Term Interval Effects of High-Intensity Interval Training on Pathways Related to Telomere Homeostasis in Rat Skeletal Muscle Iman Saffari 1 , Marziyeh Saghebjoo 1, * , Mehdi Hedayati 2 , Hadi Sarir 3 and Ivan Dimauro 4 1 Department of Exercise Physiology, Faculty of Sport Sciences, University of Birjand, Birjand, Iran 2 Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 Department of Animal Sciences, Faculty of Agriculture, University of Birjand, Birjand, Iran 4 Unit of Biology and Genetics of Movement, Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Piazza Lauro de Bosis 15, 00135 Rome, Italy * Corresponding author: Department of Exercise Physiology, Faculty of Sport Sciences, University of Birjand, Birjand, Iran. Email: m_saghebjoo@birjand.ac.ir Received 2021 December 11; Revised 2022 January 12; Accepted 2022 January 15. Abstract Background: Exercise training through various mechanisms leads to correct telomere homeostasis. The potential role of high- intensity interval training (HIIT) to keep up the telomere length has not been recognized in skeletal muscle. Objectives: This study investigated the influence of eight weeks of HIIT with short-term interval (HIITSh) and long-term interval (HIITL), and four weeks of detraining on the regulation of some pathways maintaining telomere length in skeletal muscle. Methods: Fifty-four male Wistar rats were randomly assigned into HIITSh, HIITL, and control groups. Rats were sacrificed after the end of the intervention (eight weeks of training and four weeks of detraining). Gastrocnemius muscle was collected, and telomerase activity, p53 protein, total oxidative status (TOS), and total antioxidant capacity (TAC) levels were measured. Results: We found no change in telomerase activity, p53, TOS, and TAC levels in both HIIT groups compared to the control group (P > 0.05). In addition, the p53 level was higher in the detrained HIITSh group than the control group (P = 0.004), and the TOS level was higher in the detrained HIITSh group than both HIIT groups. Conclusions: Short-term HIIT does not improve telomere length and some pathways contributing to maintaining telomere length in skeletal muscle. The training protocol’s duration is an essential factor in activating telomerase as a mechanism to keep up telom- ere length in skeletal muscle. Keywords: Telomerase Activity, High-Intensity Training, Detraining, p53 Level, Total Oxidant/Antioxidant Status 1. Background Physical activity (PA) is an inexpensive therapeutic strategy to prevent disease and extend healthspan (1). With increasing age, the physiological decline of muscle mass and strength must be counteracted to avoid the impair- ment of physical functions. Physical activity prevents func- tional decline among older people (2). Indeed, low-level PA may cause a vicious cycle that leads to disability and an in- creased incidence of adverse health outcomes. Nowadays, practicing PA as early as possible is highly recommended in the adolescent period (3). In particular, regular PA could counteract several biological characteristics of the aging process, such as oxidative stress and telomere attrition (4- 6). The telomere that is located at the end of all chromo- somes is the specialized nucleoprotein structure. It acts as a protective cap and contributes to the integrity and sta- bility of the genome (4). Telomere shortening is one of the critical hallmarks of aging and a risk factor associated with several age-related diseases such as type 2 diabetes, coro- nary artery disease, and Alzheimer’s disease (7). Some mechanisms have been identified to prevent the loss of telomere length and thus compensate for telom- ere shortening. The ribonucleic protein-enzyme complex is the most comprehensive mechanism for telomerase ex- tension. This complex synthesizes telomere repeats using a specific RNA template of the interval telomere sequence (6, 8). Human studies have shown that telomerase activ- ity is vital in germline proliferating and normal somatic cells to maintain correct telomere length homeostasis, de- laying senescence and tissue aging (9, 10). However, telom- erase activity is influenced by various environmental fac- Copyright © 2022, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.