Effect of 12-weeks high-intensity interval training on SIRT1, PGC-1α and ERRα protein expression in aged rats

Document Type : Research Paper I Open Access I Released under (CC BY-NC 4.0) license


1 PhD Student, Department of Exercise Physiology, Faculty of Physical Education and Exercise Sciences, University of Tehran, Iran.

2 Professor, Department of Exercise Physiology, Faculty of Physical Education and Exercise Sciences, University of Tehran, Iran.

3 Associate Professor, Department of Exercise Physiology, Faculty of Physical Education and Exercise Sciences, University of Tehran, Iran

4 Associate Professor, Shaheed Beheshti University of Medical Sciences Cellular and Molecular Biology Research center, Tehran, Iran


Exercise training improved impaired mitochondrial protein and enzymatic functional induced aging. The purpose of this study was to investigate the effects of 12-weeks of high-intensity interval training on mitochondrial proteins of SIRT1, PGC-1α and ERRα in gastrocnemius muscle in aged rats. In this study 30 aged Wistar rats were randomly divided into HIIT and control group. Exercise training was performed 3 days per week for 8-weeks. Exercise training in the HIIT group was started in the first week by 16 minutes (four intervals (T=2min) at 85-90% VO2max with 4 recovery periods (T=2min) at 45-50% VO2max), which reached 28 minutes in the 12th week. Gastrocnemius was removed 48 h after the final training session. The expression levels of SIRT1, PGC-1α and ERRα proteins in gastrocnemius were assessed by Western blot method. Data analysis was done with independent samples t test. There were no significant differences in body weight and gastrocnemius muscle weight after the intervention. The protein expression of PGC-1α and ERRα were significantly increased in the HIIT compared to control group (p < 0.001). Moreover, SIRT1 expression was significantly elevated in the HIIT compared to control group (P <0.01). It seems that HIIT due to its high intensity and interval nature leads to an increased expression of SIRT1, PGC-1α and ERRα proteins in the gastrocnemius muscle of aging rat models.


Main Subjects


    1. Vina J, Borras C, Miquel J. Theories of ageing. IUBMB life. 2017; 59(4):249.
    2. Wheeler HE, Kim SK. Genetics and genomics of human ageing. Philosophical Transactions of the Royal Society B: Biological Sciences. 2011; 366(1561):43-50.
    3. Khosravan SH, Alaviani M, Alami A, Tavakolizadeh J. Epidemiology of loneliness in elderly women. Journal of Research & Health. 2014; 1(4): 871-7.
    4. Handschin, C. and Spiegelman, B. M. Peroxisome proliferator-activatedreceptor gamma coactivator 1 coactivators, energy homeostasis,and metabolism. Endocrine Reviews. 2006; 27, 728–735.
    5. Brenmoehl J, Hoeflich A. Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3. Mitochondrion. 2013; 13, 755–761.
    6. Ungvari Z, Sonntag WE, Csiszar A. Mitochondria and aging in the vascular system. Journal of Molecular Medicine. 2010; 88, 1021–1027.
    7. Kang C, Chung E, Diffee G, Ji LL. Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: Role of PGC-1α Arch. Experimental Gerontology. 2013; 501, 79–90.
    8. Bori Z, Zhao Z, Koltai E, Fatouros IG, Jamurtas AZ, Douroudos II, et al. The effects of aging, physical training, and a single bout of exercise on mitochondrialprotein expression in human skeletal muscle. Experimental Gerontology. 2012; 47 (6): 417–424.
    9. Suwa M, Nakano H, Radak Z, Kumagaia S. Endurance exercise increases the SIRT1 and peroxisomeproliferator-activated receptor γ coactivator-1α protein expressions in rat skeletal muscle. Metabolism Clinical and Experimental. 2008; 57 (7): 986–998.
    10. Schreiber SN,  Emter R,  Hock MB, Knutti D, Cardenas J, Podvinec M, et al. The estrogen-related receptor α (ERRα) functions in PPARγ coactivator 1α (PGC-1α)-induced mitochondrial biogenesis. Proc Natl Acad Sci U S A. 2004; 101 (17): 6472–6477.
    11. Giguère V. Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr Rev. 2008; 29 (6):677–696.
    12. Huang CC, Wang T, Tung YT, Lin WT. Effect of exercise training on skeletal muscle SIRT1 and PGC-1α expression levels in rats of different age. International Journal of Medical Science. 2016; 13(4):260-270.
    13. Lanza IR, Nair KS. Muscle mitochondrial changes with aging and exercise. The American journal of clinical nutrition. 2009; 89(1):467S-71S.
    14. Billat LV. Interval training for performance: a scientific and empirical practice. Sports Medicine. 2001; 31(1):13-31.
    15. Seldeen KL, Lasky G, Leiker MM, Pang M, Personius KE, Troen BR. High Intensity Interval Training (HIIT) improves physical performance and frailty in aged mice. The Journals of Gerontology: Series A. 2018; 73(4):429-437.
    16. Hoydal MA, Wisloff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practicalimplications for exercise training. European Journal of Cardiovascular Prevention Rehabilitation. 2007; 14 (6):753-60.
    17. Christopher,H,. Kathryn L. Weston,. W.The effect of 12 weeks of combined upper- and lower-body high-intensity interval training on muscular and cardiorespiratory fitness in older adults” Aging Clinical and Experimental Research. 2019. 31:661–671.
    18. MacInnis MJ, Zacharewicz E, Martin BJ, Haikalis ME, Skelly LE, Tarnopolsky MA, et al. Superior mitochondrial adaptations in human skeletal muscle after interval compared to continuous single-leg cycling matched for total work. Journal of Physiology. 2017; 595(9): 2955-2968.
    19. Granata C, Oliveira RS, Little JP, Renner K, Bishop DJ. Training intensity modulates changes in PGC-1α and p53 protein content and mitochondrial respiration, but not markers of mitochondrial content in human skeletal muscle. The FASEB Journal. 2015; 30(2):959-70.
    20. Sharafi Dehrhm F, Soori R, Rastegar Mogaddam Mansouri M, Abbasian S. The effect of high intensity interval training on muscular biomarkers ofmitochondrial biogenesis in male rats. Journal of Babol University of Medical Science. 2017; 19(6): 57-63.
    21. Bartlett JD, Hwa Joo C, Jeong TS, Louhelainen J, Cochran AJ, Gibala MJ, et al. Matched work high-intensity interval and continuous running induce similar increases in PGC-1α mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle. Journal of Applied Physiology. 2012; 112(7):1135-43.
    22. Little JP, Safdar A, Wilkin GP, Tarnopolsky MA, Gibala MJ. A practical model of low volume high -intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. Journal of Physiology. 2010; 588 (6): 1011-22.
    23. Deblois G, Giguere V. Functional and physiological genomics of estrogen-related receptors (ERRs) in health and disease. Biochim Biophys Acta 2017; 1812(8): 1032-40.
    24. Cartoni R, Leger B, Hock MB, Praz M, Crettenand A, Pich S, et al. Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. J Physiol 2018; 567(1): 349-58.
    25. Green HJ, Burnett M, Carter S, Jacobs I, Ranney D, Smith I & Tupling S. Role of exercise duration on metabolic adaptations in working muscle to short-term moderate-to-heavy aerobic-based cycle training. Eur J ApplPhysiol. 2013; 113, 1965–1978.
    26. Hatle H, Støbakk PK, Mølmen HE, Brønstad E, Tjønna AE, Steinshamn S, et al . Effect of 24 sessions of high-intensity aerobic interval training carried out at either high or moderate frequency, a Randomized Trial. PLoS One. 2014;9, e88375.
    27. Hoshino D, Yoshida Y, Kitaoka Y, Hatta H and Bonen A. High-intensity interval training increases intrinsic rates of mitochondrial fatty acid oxidation in rat red and white skeletal muscle. Appl Physiol Nutr Metab. 2013; 38: 326-333.
    28. Godin R, Ascah A and Daussin FN. Intensity-dependent activation of intracellular signalling pathways in skeletal muscle: role of fibre type recruitment during exercise. Journal of Physiology. 2010; 588: 4073-4074.
    29. Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1α in human skeletal muscle. Journal of Applied Physiology. 2009; 106(3), 929-934.