Sport Physiology & Management Investigations

Sport Physiology & Management Investigations

Comparison of two models of high-intensity interval training and moderate-intensity continuous training on genes related to autophagy in heart muscle of elderly rats

Document Type : Original Article

Authors
Azadeh Taheri 1
Mandana Gholami 2
Behzad Bazgir 3
Hosein Abednatanzi 4
1 PhD student, Department of Exercise Physiology, Faculty of Literature, Humanities and Social Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 Associate Professor, Department of Physical Education and Sport Sciences, Faculty of Literature, Humanities and Social Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
3 Exercise Physiology Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
4 Assistant Professor, Department of Professional Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
10.22034/spmi.2025.414278.2515
Abstract
Aging populations experience increased cardiomyocyte death due to a decline in autophagy, a crucial anti-aging mechanism for cardiac cells. This study compared the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on autophagy-related gene expression in the cardiac muscle of elderly rats. Twenty-four aged male Wistar rats (~20 months old; 350 ± 50 g) were randomized into three groups: control (n=8), MICT (n=8), and HIIT (n=8). The 4-week exercise protocols were as follows: MICT: 5-minute warm-up (30–40% VO₂max), 30-minute continuous running (60–65% VO₂max), and cooldown. HIIT: 30-minute sessions comprising a 5-minute warm-up (30–40% VO₂max), 8 × 3-minute high-intensity intervals (85–90% VO₂max) interspersed with 2-minute active recovery (30–35% VO₂max). Gene expression (FOXO3a, Beclin-1, LC3-II) was quantified via real-time PCR. One-way ANOVA (α = 0.05) revealed: FOXO3a: HIIT significantly upregulated expression vs. control (*p* < 0.05) and MICT; no difference between MICT and control. Beclin-1: Both HIIT and MICT groups exhibited higher expression than control (*p* < 0.05), with no intergroup difference. LC3-II: Both exercise groups surpassed control levels, with HIIT showing greater elevation than MICT. Both HIIT and MICT enhance autophagy-related gene expression in aged rats, suggesting exercise-induced autophagy activation. HIIT demonstrated superior efficacy, particularly in upregulating FOXO3a and LC3-II, implicating its potential advantage for mitigating age-related cardiac autophagy decline.
Keywords
Autophagy
Continuous Training
FOXO3a
High intensity interval training
LC3-II
Beclin-1
1. Sangaralingham SJ, Wang BH, Huang L, Kumfu S, Ichiki T, Krum H, et al. Cardiorenal fibrosis and dysfunction in aging: imbalance in mediators and regulators of collagen. Peptides. 2016;76:108-14.
2. Xie J, Chen Y, Hu C, Pan Q, Wang B, Li X, et al. Premature senescence of cardiac fibroblasts and atrial fibrosis in patients with atrial fibrillation. Oncotarget. 2017;8(35):57981.
3. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147(4):728-41.
4. Akbari-Kelishomi M, Karizi S, Karimipoor M. Increased expression of Beclin1 and LC3 genes involved in autophagy in non-small cell lung cancer patients. Journal of Cell & Tissue. 2018;9(2):112-22.
5. Dejamfekr M, Ghaffari SH, Ahmadian S. Arsenic trioxide induction autophagy in human acute promyelocytic leukemia. Koomesh. 2018;20(4):764-71.
6. Zarringol M. A review on regulation of autophagy by ROS (Reactive Oxygen Species). Razi Journal of Medical Sciences. 2018;24(164):93-105.
7. Fiuza-Luces C, Delmiro A, Soares-Miranda L, González-Murillo Á, Martínez-Palacios J, Ramírez M, et al. Exercise training can induce cardiac autophagy at end-stage chronic conditions: insights from a graft-versus-host-disease mouse model. Brain, behavior, and immunity. 2014;39:56-60.
8. Jokar M, Sherafati Moghadam M, Daryanoosh F. The Effect of an 8-Week Endurance Training Program on the Content of FOXO3a and Beclin-1 Proteins in Heart Muscle of Rats With Type 2 Diabetes. Journal of Inflammatory Disease. 2020;23(6):484-93.
9. Jokar M, Sherafati Moghadam M, Daryanoosh F. The Effect of an 8-Week Endurance Training Program on the Content of FOXO3a and Beclin-1 Proteins in Heart Muscle of Rats with Type 2 Diabetes. The Journal of Qazvin University of Medical Sciences. 2020;23(6):484-93.
10. Deng Y, Wu W, Guo S, Chen Y, Liu C, Gao X, et al. Altered mTOR and Beclin-1 mediated autophagic activation during right ventricular remodeling in monocrotaline-induced pulmonary hypertension. Respiratory research. 2017;18(1):1-15.
11. Li J-Y, Pan S-S, Wang J-Y, Lu J. Changes in autophagy levels in rat myocardium during exercise preconditioning-initiated cardioprotective effects. International Heart Journal. 2019;60(2):419-28.
12. KAZEMZADEH Y, BANAEIFAR A, SHIRVANI H, GHARAAT A. THE EFFECT OF HIGH INTENSITY INTERVAL TRAINING HIIT ON BODY COMPOSITION, LIPID PROFILE AND INSULIN SENSITIVITY IN OVERWEIGHT YOUNG MEN. 2016.
13. Mejías-Peña Y, Estébanez B, Rodriguez-Miguelez P, Fernandez-Gonzalo R, Almar M, de Paz JA, et al. Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects. Aging (Albany NY). 2017;9(2):408.
14. Ferrara N, Rinaldi B, Corbi G, Conti V, Stiuso P, Boccuti S, et al. Exercise training promotes SIRT1 activity in aged rats. Rejuvenation research. 2008;11(1):139-50.
15. Marfe G, Manzi V, Tafani M, Pucci B, Gambacurta A, Russo M, et al. The modulation of sirtuins and apoptotic proteins in rats after exhaustive exercise. 2012.
16. Li F-H, Li T, Ai J-Y, Sun L, Min Z, Duan R, et al. Beneficial autophagic activities, mitochondrial function, and metabolic phenotype adaptations promoted by high-intensity interval training in a rat model. Frontiers in physiology. 2018;9:571.
17. Høydal MA, Wisløff U, Kemi OJ, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European Journal of Preventive Cardiology. 2007;14(6):753-60.
18. Kraljevic J, Marinovic J, Pravdic D, Zubin P, Dujic Z, Wisloff U, et al. Aerobic interval training attenuates remodelling and mitochondrial dysfunction in the post-infarction failing rat heart. Cardiovascular research. 2013;99(1):55-64.
19. Sultan M, Amstislavskiy V, Risch T, Schuette M, Dökel S, Ralser M, et al. Influence of RNA extraction methods and library selection schemes on RNA-seq data. BMC genomics. 2014;15(1):1-13.
20. Weng T-P, Huang S-C, Chuang Y-F, Wang J-S. Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men. PloS one. 2013;8(11):e80248.
21. Asgari Hazaveh D, Riyahi Malayeri S, Babaei S. Effect of eight weeks high intensity interval training and medium intensity interval training and aloe vera intake on serum vaspin and insulin resistance in diabetic male Rats. Journal of Arak University of Medical Sciences. 2018;20(11):67-75.
22. Jafari A, Nikookheslat S, Karimi P. THE EFFECT OF HIGH-INTENSITY INTERVAL TRAINING (HIIT) WITH AND WITHOUT CAFFEINE INJECTION ON EXPRESSION OF MYOCARDIAL AUTOPHAGY-RELATED PROTEINS IN DIABETIC RATS. Iranian Journal of Diabetes and Metabolism. 2020;19(4):183-94.
23. Lira VA, Okutsu M, Zhang M, Greene NP, Laker RC, Breen DS, et al. Autophagy is required for exercise training‐induced skeletal muscle adaptation and improvement of physical performance. The FASEB Journal. 2013;27(10):4184-93.
24. Jokar M, Sherafati Moghadam M. HIGH INTENSITY INTERVAL TRAINING INHIBITS AUTOPHAGY IN THE HEART TISSUE OF TYPE 2 DIABETIC RATS BY DECREASING THE CONTENT OF FOXO3A AND BECLIN-1 PROTEINS. Iranian Journal of Diabetes and Metabolism. 2019;18(6):292-9.
25. Tian H, Chen P, Ren J. Physical exercise, autophagy and cardiometabolic stress in aging. Aging (Albany NY). 2019;11(15):5287.
26. Biglari S, Gaeini AA, Kordi MR, GhardashiAfousi A. The Effect of 8 Weeks High-intensity Interval Training on Myostatin and Follistatin Gene Expression in Gastrocnemius Muscle of the Rats. Journal of Arak University of Medical Sciences. 2018;21(1):1-10.