The Effect of Aerobic and Resistance Training on Levels of GDF11 in Cardiac Tissue of Elderly Rats

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

Authors

1 Master of Sports Physiology, Department of Sports Science, Shahed University, Tehran, Iran

2 Assistant Professor, Department of Physical Education and Sport Sciences, Faculty of Humanities, Shahed University, Tehran, Iran.

Abstract

Aim: Aging is associated with increased functional and morphological alteration in cardiac tissue which in turn increases the risk of cardiovascular diseases. Recently Growth Differentiation Factor 11 (GDF11) is suggested as anti-aging factor in cardiac tissue, so the present study aimed at investigating the effect of aerobic and resistance training on cardiac tissue levels of GDF11 in elderly rats. Methods:  Twenty four elderly male rats were used and divided into 3 groups: control, resistance training (Climbing the ladder with a resistance of 55 to 85% of a maximum repetition, 3 sessions per week) and aerobic training (swimming with a load equal to 3-6% of body weight, 4 sessions per week, 45 minutes per session). After eight weeks, heart weight and GDF11 levels of cardiac tissue were assessed. Results:   The results of one-way analysis of variance test showed that resistance and aerobic training increased GDF11 of cardiac tissue by 5.1% and 4.6%, respectively; however, the changes were not statistically significant (p= 0.59). Also, comparing to the control group the heart to body weight ratio was 5.9% and 3% lower in both resistance and aerobic training groups, respectively (p= 0.67). Conclusions: The trend of changes in GDF11 levels and heart to body weight ratio observed in the present study supports the proposed role for GDF11 in the control of aging related pathological hypertrophy. However, it seems that training, at least with the intensity, duration and type used in the present study, does not have a significant effect on the levels of this protein. 
 

Keywords

Main Subjects


   

 

This is an open access article distributed under the following Creative Commons license: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

1.             Merchant R, Morley J, Izquierdo M. Exercise, aging and frailty: guidelines for increasing function. Springer; 2021. p. 405-9.
2.             Francois A, Canella A, Marcho LM, Stratton MS. Protein acetylation in cardiac aging. Journal of Molecular and Cellular Cardiology. 2021;157:90-7.
3.             Wei X, Wu Ye, Wang W, Zhang S, Liu D, Liu H. Decreased dynamin-related protein 1-related mitophagy induces myocardial apoptosis in the aging heart. Acta Biochimica et Biophysica Sinica. 2021;53(10):1354-66.
4.             Liang WJ, Gustafsson ÅB. The aging heart: mitophagy at the center of rejuvenation. Frontiers in Cardiovascular Medicine. 2020;7:18.
5.             Tracy E, Rowe G, LeBlanc AJ. Cardiac tissue remodeling in healthy aging: the road to pathology. American Journal of Physiology-Cell Physiology. 2020;319(1):C166-C82.
6.             Hudobenko J, Ganesh BP, Jiang J, Mohan EC, Lee S, Sheth S, et al. Growth differentiation factor-11 supplementation improves survival and promotes recovery after ischemic stroke in aged mice. Aging (Albany NY). 2020;12(9):8049.
7.             Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR, Yalamanchi P, et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell. 2013;153(4):828-39.
8.             Ma Y, Liu Y, Han F, Qiu H, Shi J, Huang N, et al. Growth differentiation factor 11: a “rejuvenation factor” involved in regulation of age-related diseases? Aging (Albany NY). 2021;13(8):12258.
9.             Zhang C, Lin Y, Liu Q, He J, Xiang P, Wang D, et al. Growth differentiation factor 11 promotes differentiation of MSCs into endothelial‐like cells for angiogenesis. Journal of cellular and molecular medicine. 2020;24(15):8703-17.
10.           Li Z, Xu H, Liu X, Hong Y, Lou H, Liu H, et al. GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3. Cell death & disease. 2020;11(10):1-10.
11.           Wang L, Wang Y, Wang Z, Qi Y, Zong B, Liu M, et al. Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2018;315(6):G909-G20.
12.           Su H-H, Liao J-M, Wang Y-H, Chen K-M, Lin C-W, Lee I-H, et al. Exogenous GDF11 attenuates non-canonical TGF-β signaling to protect the heart from acute myocardial ischemia–reperfusion injury. Basic Research in Cardiology. 2019;114(3):1-16.
13.           Du G-Q, Shao Z-B, Wu J, Yin W-J, Li S-H, Wu J, et al. Targeted myocardial delivery of GDF11 gene rejuvenates the aged mouse heart and enhances myocardial regeneration after ischemia–reperfusion injury. Basic research in cardiology. 2017;112(1):1-14.
14.           Li H, Hastings MH, Rhee J, Trager LE, Roh JD, Rosenzweig A. Targeting age-related pathways in heart failure. Circulation research. 2020;126(4):533-51.
15.           Tanaka H. Antiaging effects of aerobic exercise on systemic arteries. Hypertension. 2019;74(2):237-43.
16.           Roh J, Rhee J, Chaudhari V, Rosenzweig A. The role of exercise in cardiac aging: from physiology to molecular mechanisms. Circulation research. 2016;118(2):279-95.
17.           Tao L, Bei Y, Zhang H, Xiao J, Li X. Exercise for the heart: signaling pathways. Oncotarget. 2015;6(25):20773.
18.           Olson KA, Beatty AL, Heidecker B, Regan MC, Brody EN, Foreman T, et al. Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts. European heart journal. 2015;36(48):3426-34.
19.           Heidecker B, Spencer RM, Meyer C, Beatty AL, Whooley M, Ganz P. Low Levels of Growth Differentiation Factor 11/8 and High Levels of Its Inhibitor Follistatin-Like 3 Are Associated With Poor Exercise Capacity During a 6-Minute Walk Test. Circulation. 2016;134(suppl_1):A18014-A.
20.           Garbern J, Kristl AC, Bassaneze V, Vujic A, Schoemaker H, Sereda R, et al. Analysis of Cre-mediated genetic deletion of Gdf11 in cardiomyocytes of young mice. American Journal of Physiology-Heart and Circulatory Physiology. 2019;317(1):H201-H12.
21.           Suh J, Lee Y-S. Similar sequences but dissimilar biological functions of GDF11 and myostatin. Experimental & molecular medicine. 2020;52(10):1673-93.
22.           Harper SC, Johnson J, Borghetti G, Zhao H, Wang T, Wallner M, et al. GDF11 decreases pressure overload–induced hypertrophy, but can cause severe cachexia and premature death. Circulation research. 2018;123(11):1220-31.
23.           Chen L, Luo G, Liu Y, Lin H, Zheng C, Xie D, et al. Growth differentiation factor 11 attenuates cardiac ischemia reperfusion injury via enhancing mitochondrial biogenesis and telomerase activity. Cell Death & Disease. 2021;12(7):1-14.
24.           Zhao Y, Zhu J, Zhang N, Liu Q, Wang Y, Hu X, et al. GDF11 enhances therapeutic efficacy of mesenchymal stem cells for myocardial infarction via YME1L-mediated OPA1 processing. Stem cells translational medicine. 2020;9(10):1257-71.
25.           Zimmers TA, Jiang Y, Wang M, Liang TW, Rupert JE, Au ED, et al. Exogenous GDF11 induces cardiac and skeletal muscle dysfunction and wasting. Basic research in cardiology. 2017;112(4):1-12.
26.           Duran J, Troncoso MF, Lagos D, Ramos S, Marin G, Estrada M. GDF11 modulates Ca2+-dependent Smad2/3 signaling to prevent cardiomyocyte hypertrophy. International Journal of Molecular Sciences. 2018;19(5):1508.
27.           Garrido-Moreno V, Díaz-Vegas A, Lopez-Crisosto C, Troncoso MF, Navarro-Marquez M, García L, et al. GDF-11 prevents cardiomyocyte hypertrophy by maintaining the sarcoplasmic reticulum-mitochondria communication. Pharmacological research. 2019;146:104273.
29.           Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nature reviews Molecular cell biology. 2006;7(8):589-600.