Biomarkers and Redox Balance in Aging Rats after Dynamic and
                    Isometric Resistance Training

Rodrigo Vanerson Passos Neves; Thiago dos Santos Rosa; Hugo Luca Corrêa; Kethelen Mariana da Silva Aires; Lysleine Alves Deus; Michel Kendy Sousa; Whitley Jo Stone; Lana Ribeiro Aguiar; Jonato Prestes; Herbert Gustavo Simões; Rosângela Vieira Andrade; Milton Rocha Moraes

doi:10.1055/a-1231-5410

International Journal of Sports Medicine, Table of Contents

Int J Sports Med 2021; 42(03): 283-290
DOI: 10.1055/a-1231-5410

Genetics & Molecular Biology

Biomarkers and Redox Balance in Aging Rats after Dynamic and Isometric Resistance Training

Authors

Rodrigo Vanerson Passos Neves

¹Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil
Thiago dos Santos Rosa

¹Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil
Hugo Luca Corrêa

¹Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil
Kethelen Mariana da Silva Aires

¹Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil
Lysleine Alves Deus

¹Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil
Michel Kendy Sousa

²Nephrology Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil
Whitley Jo Stone

³School of Nutrition, Kinesiology, and Physiological Sciences, University of Central Missouri, Warrensburg, MO, United States
Lana Ribeiro Aguiar

⁴Graduate Program in Genomic Science and Biotechnology, Catholic University of Brasília, Brasília, Brazil
Jonato Prestes

¹Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil
Herbert Gustavo Simões

¹Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil
Rosângela Vieira Andrade

⁴Graduate Program in Genomic Science and Biotechnology, Catholic University of Brasília, Brasília, Brazil
Milton Rocha Moraes

¹Graduate Program in Physical Education, Catholic University of Brasília, Brasília, Brazil

Abstract

Aging muscle is prone to sarcopenia and its associated telomere shortening and increased oxidative stress. Telomeres are protected by a shelterin protein complex, proteins expressed in response to DNA damage. Aerobic exercise training has shown to positively modulate these proteins while aging, but the effects of resistance training are less clear. This investigation was to examine the role of dynamic and isometric RT on markers of senescence and muscle apoptosis: checkpoint kinase 2, 53 kDa protein, shelterin telomere repeat binding 1 and 2, DNA repair, telomere length and redox state in the quadriceps muscle. Fifteen 49-week-old male rats were divided into three groups: control, dynamic resistance training, and isometric resistance training. Dynamic and isometric groups completed five sessions per week during 16 weeks at low to moderate intensity (20–70% maximal load). Only dynamic group decreased expression of 53 kDa protein, proteins from shelterin complex, oxidative stress, and improved antioxidant defense. There was no difference among groups regarding telomere length. In conclusion, dynamic resistance training was more effective than isometric in reducing markers of aging and muscle apoptosis in elderly rats. This modality should be considered as valuable tool do counteract the deleterious effects of aging.

Key words

exercise training - telomere attrition - muscle aging - oxidative stress - antioxidant defense - apoptosis

Full Text

References

References
1 Forbes GB, Reina JC. Adult lean body mass declines with age: Some longitudinal observations. Metabolism 1970; 19: 653-663
2 Staunton L, Zweyer M, Swandulla D. et al. Mass spectrometry-based proteomic analysis of middle-aged vs. aged vastus lateralis reveals increased levels of carbonic anhydrase isoform 3 in senescent human skeletal muscle. Int J Mol Med 2012; 30: 723-733
3 Baumann CW, Kwak D, Liu HM. et al. Age-induced oxidative stress: how does it influence skeletal muscle quantity and quality?. J Appl Physiol (1985) 2016; 121: 1047-1052
4 Jang YC, Lustgarten MS, Liu Y. et al. Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration. FASEB J 2010; 24: 1376-1390
5 Oikawa S, Kawanishi S, Site-specific DNA. damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett 1999; 453: 365-368 doi:10.1016/s0014-5793(99)00748-6
6 Henle ES, Han Z, Tang N. et al. Sequence-specific DNA cleavage by Fe2+-mediated fenton reactions has possible biological implications. J Biol Chem 1999; 274: 962-971
7 di Fagagna FdA, Reaper PM, Clay-Farrace L. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003; 426: 194-198
8 Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345: 458-460
9 Galati A, Micheli E, Alicata C. et al. TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization. Nucleic Acids Res 2015; 43: 5824-5837
10 Okamoto K, Bartocci C, Ouzounov I. et al. A two-step mechanism for TRF2-mediated chromosome-end protection. Nature 2013; 494: 502-505
11 Oeseburg H, de Boer RA, van Gilst WH. et al. Telomere biology in healthy aging and disease. Pflugers Arch 2010; 459: 259-268
12 Greider CW. Telomeres. Curr Opin Cell Biol 1991; 3: 444-451
13 De Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005; 19: 2100-2110
14 Childs BG, Durik M, Baker DJ. et al. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med 2015; 21: 1424
15 Van Steensel B, De Lange T. Control of telomere length by the human telomeric protein TRF1. Nature 1997; 385: 740-743
16 Van Steensel B, Smogorzewska A, De Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell 1998; 92: 401-413
17 Smogorzewska A, van Steensel B, Bianchi A. et al. Control of human telomere length by TRF1 and TRF2. Mol Cell Biol 2000; 20: 1659-1668
18 Karlseder J, Broccoli D, Dai Y. et al. p53-and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 1999; 283: 1321-1325
19 Gibson SL, Bindra RS, Glazer PM. Hypoxia-induced phosphorylation of Chk2 in an ataxia telangiectasia mutated–dependent manner. Cancer Res 2005; 65: 10734-10741
20 Squatrito M, Brennan CW, Helmy K. et al. Loss of ATM/Chk2/p53 pathway components accelerates tumor development and contributes to radiation resistance in gliomas. Cancer Cell 2010; 18: 619-629
21 Garatachea N, Pareja-Galeano H, Sanchis-Gomar F. et al. Exercise attenuates the major hallmarks of aging. Rejuvenation Res 2015; 18: 57-89
22 Aguiar SS, Rosa TS, Sousa CV. et al. Influence of body fat on oxidative stress and telomere length of master athletes. J Strength Cond Res 2019;
23 de Carvalho Cunha VN, dos Santos Rosa T, Sales MM. et al. Training performed above lactate threshold decreases p53 and shelterin expression in mice. Int J Sports Med 2018; 39: 704-711
24 Lavin KM, Perkins RK, Jemiolo B. et al. Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation. J Appl Physiol (1985) 2020; 128: 87-99
25 No M-H, Heo J-W, Yoo S-Z. et al. Effects of aging and exercise training on mitochondrial function and apoptosis in the rat heart. Pflugers Arch 2020; 472: 179-193
26 Valenzuela PL, Maffiuletti NA, Joyner MJ. et al. Lifelong endurance exercise as a countermeasure against age-related decline: physiological overview and insights from masters athletes. Sports Med 2020; 50: 703-716
27 Melov S, Tarnopolsky MA, Beckman K. et al. Resistance exercise reverses aging in human skeletal muscle. PLoS One 2007; 2: e465
28 Vezzoli A, Mrakic-Sposta S, Montorsi M. et al. Moderate intensity resistive training reduces oxidative stress and improves muscle mass and function in older individuals. Antioxidants (Basel) 2019; 8: 431
29 Inder JD, Carlson DJ, Dieberg G. et al. Isometric exercise training for blood pressure management: a systematic review and meta-analysis to optimize benefit. Hypertension Res 2016; 39: 88-94
30 Oranchuk DJ, Storey AG, Nelson AR. et al. Isometric training and long-term adaptations: Effects of muscle length, intensity, and intent: A systematic review. Scand J Med Sci Sports 2019; 29: 484-503
31 Peters PG, Alessio HM, Hagerman AE. et al. Short-term isometric exercise reduces systolic blood pressure in hypertensive adults: possible role of reactive oxygen species. Int J Cardiol 2006; 110: 199-205
32 Neves RVP, Rosa TS, Souza MK. et al. Dynamic, not isometric resistance training improves muscle inflammation, oxidative stress and hypertrophy in rats. Front Physiol 2019; 10: 4
33 Harriss D, MacSween A, Atkinson GJIJoSM. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817
34 O’Callaghan NJ, Fenech MJBpo. A quantitative PCR method for measuring absolute telomere length. Biol Proced Online 2011; 13: 3
35 Chandrasekaran A, Idelchik MdPS, Melendez JA. Redox control of senescence and age-related disease. Redox Biol 2017; 11: 91-102
36 Shay JW, Wright WE. Telomeres and telomerase: three decades of progress. Nat Rev Genet 2019; 20: 299-309
37 Beyfuss K, Hood DA. A systematic review of p53 regulation of oxidative stress in skeletal muscle. Redox Rep 2018; 23: 100-117
38 Mantovani F, Collavin L, Del Sal G. Mutant p53 as a guardian of the cancer cell. Cell Death Differ 2019; 26: 199-212
39 Lane DP. Cancer. p53, guardian of the genome. Nature 1992; 358: 15-16
40 Fox DK, Ebert SM, Bongers KS. et al. p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization. Am J Physiol Endocrinol Metab 2014; 307: E245-E261
41 Qi Z, He J, Zhang Y. et al. Exercise training attenuates oxidative stress and decreases p53 protein content in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. Free Radic Biol Med 2011; 50: 794-800
42 Davalli P, Mitic T, Caporali A. et al. ROS, cell senescence, and novel molecular mechanisms in aging and age-related diseases. Oxid Med Cell Longev 2016; 2016: 3565127.
43 Botha M, Grace L, Bugarith K. et al. The impact of voluntary exercise on relative telomere length in a rat model of developmental stress. BMC Res Notes 2012; 5: 697
44 Calado RT, Dumitriu B. Telomere dynamics in mice and humans. Semin Hematol 2013; 50: 165-174
45 Werner C, Furster T, Widmann T. et al. Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall. Circulation 2009; 120: 2438-2447
46 Chen Y, Liu K, Shi Y et al. The tango of ROS and p53 in tissue stem cells. Cell Death Differ 2018; 25: 639–641
47 Hwang J-w, Yao H, Caito S. et al. Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med 2013; 61: 95-110
48 Wang P, Zhang S-D, Jiao J. et al. ROS-mediated p53 activation by juglone enhances apoptosis and autophagy in vivo and in vitro. Toxicol Appl Pharmacol 2019; 379: 114647