EGZERSİZ ANTRENMAN ADAPTASYON FARKLILIKLARININ GENETİK AÇIDAN İNCELENMESİ

Yıl 2019, Cilt: 13 Sayı: 2, 66 - 79, 01.08.2019

Beste Tacal Aslan Başak Funda Eken Korkut Ulucan

Öz

Düzenli egzersiz toplum sağlığı açısından çok önemli olmakla birlikte ve fiziksel aktivitenin de desteklenmesi ayrı bir önem arz etmektedir. Uzun dönem, bireye özel uygun dozda, düzenli uygulanan egzersizin, kardiyovasküler sistem, kas-iskelet sistemi, endokrin sistemi üzerine ve ayrıca psikolojiye de olumlu etkilerinin olduğu bilinmektedir. Bunun aksine sedanter yaşam diğer bir ifadeyle fiziksel inaktivite, beraberinde birçok hastalığı getirmektedir. Günümüze kadar diyabet, obezite, kardiyovasküler hastalıklar ve bunun yanında kas gücü ve boyutu, hemodinamik çeşitlilikler üzerine yapılan çok sayıda çalışmadan elde edilen sonuçlar doğrultusunda genetik polimorfizmlerin egzersiz adaptasyonuna etkisinin olduğu belirtilmektedir. Aynı zamanda uygulanan egzersiz programlarının tipi, süresi ve şiddeti de nöro-motor ve kardiyovasküler gibi sistemler üzerinde ve genetik yapıda oluşan değişiklikleri çeşitlendirmektedir. Egzersize oluşacak yanıtlar, akut ve kronik cevaplar ve adaptasyonlar olarak da farklılaşmaktadır. Bu derlemede inceleyeceğimiz çalışmaların odak noktası genel olarak egzersiz ve fiziksel aktivitede fenotip adaptasyonların doğrudan incelenmesidir. Bu alandaki çalışmalara 2009 yılından sonra daha da yoğunluk verilmeye başlanmıştır. Ayrıca egzersiz eğitimi ile verilen yanıtlardan ziyade bireylerin günlük yaşamını etkileyen fiziksel aktiviteleri de inceleyen çok sayıda çalışma bulunmaktadır. Bu derlemede egzersizlerin vücutta oluşturduğu yanıtlar, genetik açıdan güncel literatür ışığında ele alınmaktadır.

Anahtar Kelimeler

polimorfizm, egzersiz, yaşam tarzı modifikasyonu

GENETIC ANALYSIS OF DIFFERENCES OF EXERCISE TRAINING ADAPTATIONS

Öz

Regular exercise is very important to the health of society and the promotion of physical activity also poses a particular importance. It is known that if exercise is regularly, long period and appropriate dose administered to individual, has positive effects on cardiovascular system, musculoskeletal system, endocrine system and also psychology. In contrast, sedentary life, in other words physical inactivity, brings many diseases. To date, in accordance with the results obtained from a large number of studies about diabetes, obesity, cardiovascular diseases, as well as muscle strength and size, and also hemodynamic variables, genetic polymorphisms have been reported to have an effect on exercise adaptation. At the same time, differences of the type, duration and severity of the exercise programs affect the changes of the genetic structure of the systems such as the neuro-motor system, the cardiovascular system. The responses to exercise differ in both acute and chronic responses and adaptations. The focus of this review is the studies of genetic investigation of adaptations in exercise and physical activity in general. Studies in this area have started to be intensified after 2009. In addition the responses of exercise training to the body are discussed in the light of the current literature

Anahtar Kelimeler

polimorfizm, excercise, life style modification

Kaynakça

• -1. Ahmetov I.I., Williams A.G., Popov D.V., Lyubaeva E.V., Hakimullina A.M. ve ark., “The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes” Hum Genet.126.pp.751–776, 2009.
• 2. Ahmetov I. I., Kulemin N. A., Popov D. V., Naumov V. A., Akimov E. B., Bravy Y. ve ark., “Genome-wide association study identifies threenovel genetic markers associated with elite endurance performance” Biology of Sport. 32, 3– 9, 2015
• 3. Argyropoulos G., Stutz A.M, Ilnytska O., Rice T., Teran-Garcia M., Rao D.C., Bouchard C., Rankinen T., “KIF5B gene sequence variation and response of cardiac stroke volume to regular exercise” Physiological Genomics.36:pp.79–88, 2009.
• 4. Bacci S., De Cosmo S., Prudente S. ve Trischitta V., “ENPP1 gene, insulin resistance and related clinical outcomes” Current Opinion in Clinical Nutrition and Metabolic Care.10.pp.403–409, 2007.
• 5. Bamman M.M., Petrella J.K., Kim J.S., Mayhew D.L., Cross J.M., “Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans”. The Journal of Applied Physiology. 102: 2232–2239, 2007.
• 6. Baturin A.K., Pogozheva A.V., Sorokina E., Makurina O.N., Tutel’ian V.A., “The Trp64Arg polymorphism of beta3-adrenoreceptor gene study in persons with overweight and obesity” Vopr Pitan.81.pp.23–27, 2012.
• 7. Beer N.L., Tribble N.D., Mcculloch L.J., Roos C., Johnson P.R., Orho-Melander M., Gloyn A.L., “The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver” Human Molecular Genetics.18.pp.4081–4088, 2009.
• 8. Bouchard C., Leon A.S., Rao D.C., Skinner J.S., Wilmore J.H., Gagnon J., “THE HERITAGE family study. Aims, design, and meausurement protocol” Medicine & Science in Sports & Exercise. 27.pp.721-729, 1995.
• 9. Bouchard C., An P. ,Rice T., Skinner J.S. , Wilmore J.H., Gagnon J., Pérusse L., Leon A.S., Rao D.C., “Familial Aggregation of VO2max response to exercise training:results from the HERİTAGE Family study” The Journal of Applied Physiology. 87.pp.1003-1008, 1999.
• 10. Bouchard C., Sarzynski M.A., Rice T.K., Kraus W.E., Church T.S., Sung Y.J., ve ark., “Genomic predictors of the maximal O2 uptake response to standardized exercise training programs” The Journal of Applied Physiology.pp.110.1160– 1170, 2011.
• 11. Boulé N. G., Weisnagel S. J., Lakka T. A., Tremblay A., Bergman R. N., Rankinen T., et al., “Effects of exercise training on glucose homeostasis: the HERITAGE family study” Diabetes Care 28.pp.108–114, 2005.
• 12. Chew A., Buck E.A., Peretz S., Sirugo G., Rinaldo P., Isaya G., “Cloning, expression, and chromosomal assignment of the human mitochondrial intermediate peptidase gene (MIPEP)” Genomics.40:493-6, 1997.
• 13. Chew A., Sirugo G., Alsobrook 2nd J.P., Isaya G., “Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin” Genomics.65(2):104–12, 2000.
• 14. Clarkson P.M., Devaney J.M., GordishDressman H., ve ark., “ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women” The Journal of Applied Physiology. 99:154–63, 2005.
• 15. Devaney J.M., Tosi L.L., Fritz D.T., GordishDressman H.A., Jiang S., Orkunoglu-Suer F.E., Gordon A.H., Harmon B.T., Thompson P.D., Clarkson P.M. ve ark., “Differences in fat and muscle mass associated with a functional human polymorphism in a post-transcriptional BMP2 gene regulatory element. The Journal of Cellular Biochemistry 107:1073–1082, 2009.
• 16. Eynon N., Nasibulina E.S., Banting L.K., Cieszczyk P., Maciejewska-Karlowska A., Sawczuk M., Bondareva E.A., Shagi-mardanova R.R., Raz M., Sharon Y., Williams A.G., Ahmetov I.I., Lucia A., Birk R., “The FTO A/T polymorphism and elite athletic performance: a study involving three groups of European athletes” PLoS One .pp.8:e60570, 2013.
• 17. Fawcett K.A., ve Barroso I., “The genetics of obesity: FTO leads the way” Trends in Genetics.pp.26.266–274, 2010.
• 18. Franks P.W., Jablonski K.A., Delahanty L.M., McAteer J.B., Kahn S.E. ve ark., “Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity- related traits in the Diabetes Prevention Program” Diabetologia. 51.pp.2214–2223, 2008.
• 19. Hand B.D., Kostek M.C., Ferrell R.E., et al., “Influence of promoter region variants of insulinlike growth factor pathway genes on the strength-training response of muscle phenotypes in older adults” Journal of Applied Physiology.103:1678–87, 2007.
• 20. Harmon B.T., Orkunoglu-Suer E.F., Adham K., Larkin J.S., Gordish-Dressman H., Clarkson P.M., Thompson P.D., Angelopoulos T.J., Gordon P.M., Moyna N.M. ve ark., “CCL2 and CCR2 variants are associated with skeletal muscle strength and change in strength with resistance training” Journal of Applied Physiology.109, 1779–1785, 2010.
• 21. Hivert M.F., Jablonski K.A., Perreault L., Saxena R., McAteer J.B., Franks P.W., “Updated genetic score based on 34 confirmed type 2 diabetes Loci is associated with diabetes incidence and regression to normoglycemia in the diabetes prevention program” Diabetes. 60.pp.1340– 1348, 2011.
• 22. Hoffman E.P., Gordish-Dressman H., McLane V.D., Devaney J.M., Thompson P.D., Visich P., Gordon P.M., Pescatello L.S., Zoeller R.F., Moyna N.M., ve ark., “Alterations in osteopontin modify muscle size in females in both humans and mice” Medicine & Science in Sports & Exercise. 45(6):1060-8, 2013.
• 23. Hoggart C.J., Venturini G., Mangino M., Gomez F., Ascari G., Zhao J.H., Teumer A., Winkler T.W., Tsernikova N., Luan J., ve ark., “Novel approach identifies SNPs in slc2a10 and kcnk9 with evidence for parent-of-origin effect on body mass index” PLOS Genetics. 10.pp.e1004508, 2014.
• 24. Huffman K.M., Shah S.H., Steverns R.D., Bain J.R., Muehlbauer M., Slentz C.A. ve ark., “Relationships between circulating metabolic intermediates and insulin action in overweight to obese inactive men and women” Diabetes Care. 32.pp.1678-1683, 2009.
• 25. Huffman K.M., Slentz C.A., Bateman L.A., Thompson D., Muehlbauer M.J., Bain J.R., ve ark., “Exercise- induced changes in metabolic ıntermediates, hormones, and ınflammatory markers associated with improvements in insulin sensitivity” Diabetes Care.34.pp. 174-176, 2011.
• 26. Huggins G.S., Papandonatos G.D., Erar, B., Belalcazar L.M., Brautbar A., Ballantyne C., Kitabchi A.E., Wagenknecht L.E., Knowler W.C., Pownall H.J., ve ark., “Do Genetic Modifiers of High-Density Lipoprotein Cholesterol and Triglyceride Levels Also Modify Their Response to a Lifestyle Intervention in the Setting of Obesity and Type-2 Diabetes Mellitus?” Circulation: Cardiovascular Genetics. 6.pp.391– 399, 2013.
• 27. Kebede M.A., Attie A.D., “Insights into obesity and diabetes at the intersection of mouse and human genetics” Trends in Endocrinology & Metabolism.25.pp.493-501, 2014.
• 28. Kilpeläinen T.O., Lakka T.A., Laaksonen D.E., Mager U., Salopuro T., Kubaszek A., et al., “Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study” Metabolism. 57(3).pp.428–436, 2008a.
• 29. Kilpelainen T.O., Lakka T.A., Laaksonen D.E., Lindstrom J., Eriksson J.G., Valle T.T., Hamalainen H., Ilanne-Parikka P., KeinanenKiukaanniemi S., Lindi V., Tuomilehto J., Uusitupa M., Laakso M., “SNPs in PPARG associate with type 2 diabetes and interact with physical activity” Medicine & Science in Sports & Exercise. 40(1).pp.25–33, 2008b.
• 30. Kilpeläinen T.O., Qi L., Brage S., Sharp S.J., Sonestedt E., Demerath E., ve ark., “Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children” PLOS Medicine.8(11).pp.e1001116, 2011.
• 31. Kostek M.C., Delmonico M.J., Reichel J.B., Roth S.M., Douglass L., Ferrell R.E., Hurley B.F., “Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults” Journal applied of Physiology.98:2147–54, 2005.
• 32. Kraus W.E., Torgan C.E., Duscha B.D., Norris J., Brown S.A., Cobb F.R., ve ark., “Studies of a targeted risk reduction intervention through defined exercise (STRRIDE)” Medicine & Science in Sports & Exercise.33.pp. 1774–1784, 2001.
• 33. Lakka T. A., Rankinen T., Weisnagel S. J., Chagnon Y. C., Rice T., Leon A. S., ve ark., “A quantitative trait locus on 7q31 for the changes in plasma insulin in response to exercise training: the HERITAGE Family Study” Diabetes/Metabolism Research and Reviews.52.pp. 1583–1587, 2003.
• 34. Lakka T.A., Rankinen T., Weisnagel S.J., Chagnon Y.C., Lakka H.M., Ukkola O., Boulé N., Rice T., Leon A.S., Skinner J.S., Wilmore J.H., Rao D.C., Bergman R., Bouchard C., “Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: The HERITAGE family study” Diabetes.53(6).pp.1603-1608, 2004.
• 35. Lappalainen T.J., Tolppanen A.M., Kolehmainen M., Schwab U., Lindstro ̈m J., et al., “The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: The Finnish Diabetes Prevention Study” Obesity.17.pp.832–836, 2009.
• 36. Linke W.A. ve Hamdani N., “Gigantic business: titin properties and function through thick and thin” Circulation Research.114(6).pp.1052-68, 2014.
• 37.Locke A.E. ve ark., “Genetic studies of body mass index yield new insights for obesity Biology” Nature 518, 197–206, 2015.
• 38. Loos R.J., Hagberg J.M., Pe ́ russe L., Roth S.M., Sarzynski M.A., Wolfarth B., Rankinen T. ve Bouchard C., “Advances in exercise, fitness, and performance genomics in 2014” Medicine & Science in Sports & Exercise. 47.pp.1105–1112, 2015.
• 39. Loughna P.T., Msaon P., Bayol S., Brownson C., “The LIM-domain protein FHL1 (SLIM 1) exhibits functional regulation in skeletal muscle” Molecular Cell Biology Research Communications.3.pp.136–140, 2000.
• 40. Margolis L.M. ve Pasiakos S.M., “Optimizing intramuscular adaptations to aerobic exercise: effects of carbohydrate restriction and protein supplementation on mitochondrial biogenesis” Advances in Nutrition. 4(6).pp.657-64, 2013.
• 41. Mitchell J.A., Church T.S., Rankinen T., Earnest C.P., Sui X. ve ark., “FTO genotype and the weight loss benefits of moderate intensity exercise” Obesity.18.pp.641–643, 2010.
• 42. Moore A.F., Jablonski K.A., Mason C.C. ve ark., “The association of ENPP1 K121Q with diabetes incidence is abolished by lifestyle modification in the Diabetes Prevention Program” The Journal of Clinical Endocrinology and Metabolism.94.pp.449–55, 2009.
• 43. Pan Q., Delahanty L.M., Jablonski K.A. ve ark., “Variation at the melanocortin 4 receptor gene and response to weight‐loss interventions in the diabetes prevention program” Obesity.21.pp.E520–E526, 2013.
• 44. Pescatello L.S., Kostek M.A., GordishDressman H., ve ark., “ACE ID genotype and the muscle strength and size response to unilateral resistance training” Medicine & Science in Sports & Exercise.38(6):1074–81, 2006.
• 45. Pescatello L.S., Devaney J.M., Hubal M.J., Thompson P.D., Hoffman E.P., “Highlights from the functional single nucleotide polymorphisms associated with human muscle size and strength or FAMuSS study” BioMed Research International 2013: 643575, 2013.
• 46. Petrella J.K., Kim J.S., Mayhew D.L., Cross J.M., Bamman M.M. “Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis” Journal of Applied Physiology 104: 1736 –1742, 2008.
• 47. Phillips B.E., Williams J.P., Gustafsson T., Bouchard C., Rankinen T., Knudsen S., Smith K., Timmons J.A., Atherton P.J., “Molecular networks of human muscle adaptation to exercise and age” PLoS Genet 9, e1003389, 2013.
• 48. Pickering C. ve Kiely J., “Understanding personalized training responses: can genetic assessment help?” The Open Sports Sciences Journal 10,2017.
• 49. Pollin T.I., Jablonski K.A., McAteer J.B., Saxena R., Kathiresan S., Kahn S.E. ve ark., “Triglyceride response to an intensive lifestyle intervention is enhanced in carriers of the GCKR Pro446Leu polymorphism” The Journal of Clinical Endocrinology and Metabolism.96(7).pp.E1142–E1147, 2011.
• 50. Pollin T.I., Isakova T., Jablonski K.A., de Bakker P.I., Taylor A., McAteer J. ve ark., “Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: The Diabetes Prevention Program” PLoS Genetics.8(8):.pp.1002895, 2012.
• 51. Raimondo A., Rees M.G., Gloyn A.L., “Glucokinase regulatory protein: complexity at the crossroads of triglyceride and glucose metabolism” Current Opinion in Lipidology.26(2).pp. 88-95, 2015.
• 52. Rangwala S.M. ve ark., “Peroxisome proliferator-activated receptor gamma in diabetes and metabolism” Trends in Pharmacological Sciences.25.pp.331–336, 2004.
• 53. Rankinen T., An P., Pérusse L. ve ark., “Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study” Physiological Genomics.10.pp.57-62, 2002.
• 54. Rankinen T., Rice T., Teran-Garcia M., Rao D.C., Bouchard C., “FTO genotype is associated with exercise training-induced changes in body composition” Obesity.18.pp.322–326, 2009.
• 55. Rankinen T., Argyropoulos G., Rice T., Rao D.C., Bouchard C., “CREB1 is a strong genetic predictor of the variation in exercise heart rate response to regular exercise: the HERITAGE Family Study” Circulation: Cardiovascular Genetics.3(3).pp.294–299, 2010.
• 56. Riechman S.E., Balasekaran G., Roth S.M., Ferrell R.E. “Association of interleukin-15 protein architecture of adult human height” Nature Genetics.46, 1173–1186, 2014. and interleukin-15 receptor genetic variation with resistance exercise training responses” Journal of Applied Physiology.97: 2214–2219, 2004.
• 57. Ruchat S.M., Rankinen T., Weisnagel S.J., Rice T., Rao D.C., Bergman R.N. ve ark., “Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study” Diabetologia. 53.pp.679–689, 2010.
• 58. Sailer C. ve ark., “FTO genotype interacts with improvement in aerobic fitness on body weight loss during lifestyle intervention” Obesity Facts.9(3).pp.174–181, 2016.
• 59. Santiago C., Ruiz J.R., Buxens A., Artieda M., Arteta D. ve ark., “Trp64Arg polymorphism in ADRB3 gene is associated with elite endurance performance” British Journal of Sports Medicine.45.pp.147–149, 2011.
• 60. Spielmann N., Leon A.S., Rao D.C., Rice T., Skinner J.S., Rankinen T. ve ark., “Genomewide linkagee scan for submaximal exercise heart rate in the HERITAGE family study” The American Journal of Physiology.293.pp.H3336- H3371, 2007.
• 61. Teran-Garcia M., Santoro N., Rankinen T. ve ark., “Hepatic lipase gene variant -514C>T is associated with lipoprotein and insulin sensitivity response to regular exercise: the HERITAGE Family Study” Diabetes.54.pp.2251–2255, 2005.
• 62. Teran-Garcia, M., Rankinen, T., Rice, T., Leon, A.S., Rao, D.C., Skinner, J. S. ve ark., “Variations in the four and a half LIM domains 1 gene (FHL1) are associated with fasting insulin and insulin sensitivity responses to regular exercise” Diabetologia. 50.pp.1858–1866, 2007.
• 63. Teslovich T.M., Musunuru K., Smith A.V., Edmondson A.C., Stylianou I.M., Koseki M., Pirruccello J.P., Ripatti S., Chasman D.I., Willer C.J. ve ark., “Biological, clinical and population relevance of 95 loci for blood lipids” Nature.466.pp.707–713, 2010.
• 64. Thalacker-Mercer A., Stec M., Cui X., Cross J., Windham S., Bamman M., “Cluster analysis reveals differential transcript profiles associated with resistance training-induced human skeletal muscle hyper-trophy” Physiological Genomics.45, 499 –507, 2013.
• 65. Thiebaud D., Jacot E., DeFronzo R.A., Maeder E., Jequier E., Felber J.P., “The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man” Diabetes. 31.pp.957–963, 1982.
• 66. Thomaes T., Thomis M., Onkelinx S., Fagard R., Matthijs G., Buys R. Ve ark., “A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CARAGENE study” BMC Genetics.12.pp.84, 2011.
• 67. Timmons J.A., Knudsen S., Rankinen T., Koch L.G., Sarzynski M., Jensen T. ve ark., “Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans” Journal of Applied Physiology.108.pp.1487–1496, 2010.
• 68. Venezia A.C. ve Roth S.M., “Recent research in the genetics of exercise and training adaptation” In Genetics and sport, eds. M. Posthumus, and M. Collins, 29–40. Basel: Karger, 2016.
• 69. Wadden T.A., West D.S., Delahanty L., Jakicic J., Rejeski J., Williamson D., Berkowitz R.I., Kelley D.E., Tomchee C., Hill J.O., Kumanyika S., “The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it” Obesity (Silver Spring).14(5).pp.737–52, 2006.
• 70. Walsh S., Kelsey B. K., Angelopoulos T. J., Clarkson P. M., Gordon P. M., Moyna N.M. ve ark., “CNTF 1357 G-A polymorphism and the muscle strength response to resistance training” Journal of Applied Physiology.107,1235–1240, 2009.
• 71. Warburton D.E., Nicol C.W. ve Bredin, S.S., “Health benefits of physical activity: the evidence” Canadian Medical Association Journal. 174.pp.801-809, 2006.
• 72. Wen W., Zheng W., Okada Y., Takeuchi F., Tabara Y., Hwang J.Y. ve ark., “Meta-analysis of genome-wide association studies in East Asianancestry populations identifies four new loci for body mass index” Human Molecular Genetics.23.pp.5492–5504, 2014.
• 73. Willer C.J., Schmidt E.M., Sengupta S., Peloso G.M., Gustafsson S., Kanoni S. ve ark., “Discovery and refinement of loci associated with lipid levels” Nature Genetics. 45.pp.1274– 1283, 2013.
• 74. Wolfarth B., Rankinen T., Muhlbauer S., Scherr J., Boulay M.R. ve ark., “Association between a beta2-adrenergic receptor polymorphism and elite endurance performance” Metabolism. 56.pp.1649–1651, 2007.
• 75. Wood A.R., ve ark., “Defining the role of common variation in the genomic and biologicaarchitecture of adult human height” Nature Genetics.46, 1173–1186, 2014.
• 76. Zarebska A., Jastrzebski Z., Kaczmarczyk M., Ficek K., Maciejewska-Karlowska A., Sawczuk M. ve ark., “The GSTP1 c.313A>G polymorphism modulates the cardiorespiratory response to aerobic training” Biology of Sport.31.pp.261–266, 2014.