Biology of VO2max: looking under the physiology lamp

Acta Physiologica

Volumn 220, Issue 2, 2017, Pages 218-228

  Lundby, C ^a   Montero, D ^b   Joyner, M ^c  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^c MAYO CLINIC   (United States)

Author keywords

exercise; genetics; mitochondria; non responders; performance; red blood cell volume

Indexed keywords

DNA; HEMOGLOBIN; OXYGEN;

ADAPTATION; ATHLETE; BLOOD VOLUME; CARDIORESPIRATORY FITNESS; CROSS-SECTIONAL STUDY; ENDURANCE TRAINING; ERYTHROCYTE; ERYTHROCYTE VOLUME; ERYTHROPOIESIS; EXERCISE INTENSITY; EXERCISE PHYSIOLOGY; GENETIC ANALYSIS; GENETIC VARIABILITY; HEART STROKE VOLUME; HEART VENTRICLE COMPLIANCE; HEMATOCRIT; HEMOGLOBIN BLOOD LEVEL; HUMAN; MAXIMAL OXYGEN UPTAKE; MOLECULAR BIOLOGY; OXYGEN CONSUMPTION; PRIORITY JOURNAL; REVIEW; STIMULUS; ANIMAL; CARDIOVASCULAR FUNCTION; ENDURANCE; PHYSIOLOGY; RESPIRATORY FUNCTION;

ANIMALS; CARDIOVASCULAR PHYSIOLOGICAL PHENOMENA; HUMANS; OXYGEN CONSUMPTION; PHYSICAL ENDURANCE; RESPIRATORY PHYSIOLOGICAL PHENOMENA;

EID: 85006355710     PISSN: 17481708     EISSN: 17481716     Source Type: Journal    
DOI: 10.1111/apha.12827     Document Type: Review

References (110)

1. Arbab-Zadeh, A., Perhonen, M., Howden, E., Peshock, R.M., Zhang, R., Adams-Huet, B., Haykowsky, M.J. & Levine, B.D. 2014. Cardiac remodeling in response to 1 year of intensive endurance training. Circulation 130, 2152–2161.
2. Astrand, P.O. & Rodahl, K. 1986. Chapter 10: physical training. In: D.B.V. Dalen, (ed) Textbook of Work Physiology, pp. 412–485. McGraw-Hill Book Company, Singapore.
3. Bacon, A.P., Carter, R.E., Ogle, E.A. & Joyner, M.J. 2013. VO2max trainability and high intensity interval training in humans: a meta-analysis. PLoS ONE 8, e73182.
4. Bassett, D.R. Jr & Howley, E.T. 1997. Maximal oxygen uptake: “classical” versus “contemporary” viewpoints. Med Sci Sports Exerc 29, 591–603.
5. Beere, P.A., Russell, S.D., Morey, M.C., Kitzman, D.W. & Higginbotham, M.B. 1999. Aerobic exercise training can reverse age-related peripheral circulatory changes in healthy older men. Circulation 100, 1085–1094.
6. Bodary, P.F., Pate, R.R., Wu, Q.F. & McMillan, G.S. 1999. Effects of acute exercise on plasma erythropoietin levels in trained runners. Med Sci Sports Exerc 31, 543–546.
7. Bonne, T.C., Doucende, G., Fluck, D., Jacobs, R.A., Nordsborg, N.B., Robach, P., Walther, G. & Lundby, C. 2014. Phlebotomy eliminates the maximal cardiac output response to six weeks of exercise training. Am J Physiol Regul Integr Comp Physiol 306, R752–R760.
8. Bouchard, C., Sarzynski, M.A., Rice, T.K., Kraus, W.E., Church, T.S., Sung, Y.J., Rao, D.C. & Rankinen, T. 2011. Genomic predictors of the maximal O2 uptake response to standardized exercise training programs. J Appl Physiol (1985) 110, 1160–1170.
9. Bouchard, C., Blair, S.N., Church, T.S., Earnest, C.P., Hagberg, J.M., Häkkinen, K., Jenkins, N.T., Karavirta, L., Kraus, W.E., Leon, A.S., Rao, D.C., Sarzynski, M.A., Skinner, J.S., Slentz, C.A. & Rankinen, T. 2012. Adverse metabolic response to regular exercise: is it a rare or common occurrence? PLoS ONE 7, e37887.
10. Boushel, R., Gnaiger, E., Calbet, J.A., Gonzalez-Alonso, J., Wright-Paradis, C., Sondergaard, H., Ara, I., Helge, J.W. & Saltin, B. 2011. Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans. Mitochondrion 11, 303–307.
11. Bray, M.S., Hagberg, J.M., Perusse, L., Rankinen, T., Roth, S.M., Wolfarth, B. & Bouchard, C. 2009. The human gene map for performance and health-related fitness phenotypes: the 2006-2007 update. Med Sci Sports Med 41, 35–73.
12. Brink-Elfegoun, T., Kaijser, L., Gustafsson, T. & Ekblom, B. 2007. Maximal oxygen uptake is not limited by a central nervous system governor. J Appl Physiol (1985), 102, 781–786.
13. Brotherhood, J., Brozovic, B. & Pugh, L.G. 1975. Haematological status of middle- and long-distance runners. Clin Sci Mol Med 48, 139–145.
14. Calbet, J.A., Lundby, C., Sander, M., Robach, P., Saltin, B. & Boushel, R. 2006a. Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans. Am J Physiol Regul Integr Comp Physiol 291, R447–R453.
15. Calbet, J.A.L., Lundby, C., Koskolou, M. & Boushel, R. 2006b. Importance of hemoglobin concentration to exercise: acute manipulations. Respir Physiol Neurobiol 151, 132–140.
16. Calbet, J.A., Losa-Reyna, J., Torres-Peralta, R., Rasmussen, P., Ponce-Gonzalez, J.G., Sheel, A.W., de la Calle-Herrero, J., Guadalupe-Grau, A., Morales-Alamo, D., Fuentes, T., Rodriguez-Garcia, L., Siebenmann, C., Boushel, R. & Lundby, C. 2015. Limitations to oxygen transport and utilization during sprint exercise in humans: evidence for a functional reserve in muscle O2 diffusing capacity. J Physiol 593, 4649–4664.
17. Convertino, V.A. 2007. Blood volume response to physical activity and inactivity. Am J Med Sci 334, 72–79.
18. Convertino, V.A., Mack, G.W. & Nadel, E.R. 1991. Elevated central venous pressure: a consequence of exercise training-induced hypervolemia? Am J Physiol 260, R273–R277.
19. Coyle, E.F., Hemmert, M.K. & Coggan, A.R. 1986. Effects of detraining on cardiovascular responses to exercise: role of blood volume. J Appl Physiol (1985) 60, 95–99.
20. Davies, K.J., Maquire, J.J., Brooks, G.A., Dallman, P.R. & Packer, L. 1982. Muscle mitochondrial bioenergetics, oxygen supply, and work capacity during dietary iron deficiency and repletion. Am J Physiol 242, 418–427.
21. Dill, D.B., Braithwaite, K., Adams, W.C. & Bernauer, E.M. 1974. Blood volume of middle-distance runners: effect of 2,300-m altitude and comparison with non-athletes. Med Sci Sports 6, 1–7.
22. Ehsani, A.A., Ogawa, T., Miller, T.R., Spina, R.J. & Jilka, S.M. 1991. Exercise training improves left ventricular systolic function in older men. Circulation 83, 96–103.
23. Ekblom, B., Astrand, P.O., Saltin, B., Stenberg, J. & Wallstrom, B. 1968. Effect of training on circulatory response to exercise. J Appl Physiol 24, 518–528.
24. Emerson, G.G. & Segal, S.S. 1997. Alignment of microvascular units along skeletal muscle fibers of hamster retractor. J Appl Physiol (1985) 82, 42–48.
25. Engel, A. & Pagel, H. 1995. Increased production of erythropoietin after application of antidiuretic hormone. A consequence of renal vasoconstriction? Exp Clin Endocrinol Diabetes 103, 303–307.
26. Fleg, J.L., Schulman, S.P., O'Connor, F.C., Gerstenblith, G., Becker, L.C., Fortney, S., Goldberg, A.P. & Lakatta, E.G. 1994. Cardiovascular responses to exhaustive upright cycle exercise in highly trained older men. J Appl Physiol (1985) 77, 1500–1506.
27. Fujimoto, N., Prasad, A., Hastings, J.L., Arbab-Zadeh, A., Bhella, P.S., Shibata, S., Palmer, D. & Levine, B.D. 2010. Cardiovascular effects of 1 year of progressive and vigorous exercise training in previously sedentary individuals older than 65 years of age. Circulation 122, 1797–1805.
28. Gleser, M.A. 1973. Effects of hypoxia and physical training on hemodynamic adjustments to one-legged exercise. J Appl Physiol 34, 655–659.
29. Haennel, R., Teo, K.K., Quinney, A. & Kappagoda, T. 1989. Effects of hydraulic circuit training on cardiovascular function. Med Sci Sports Exerc 21, 605–612.
30. Hawkins, M.N., Raven, P.B., Snell, P.G., Stray-Gundersen, J. & Levine, B.D. 2007. Maximal oxygen uptake as a parametric measure of cardiorespiratory capacity. Med Sci Sports Exerc 39, 103–107.
31. Hawley, J.A., Hargreaves, M., Joyner, M.J. & Zierath, J.R. 2014. Integrative biology of exercise. Cell 159, 738–749.
32. Heinicke, K., Wolfarth, B., Winchenbach, P., Biermann, B., Schmid, A., Huber, G., Friedmann, B. & Schmidt, W. 2001. Blood volume and hemoglobin mass in elite athletes of different disciplines. Int J Sports Med 22, 504–512.
33. Helgerud, J., Hoydal, K., Wang, E., Karlsen, T., Berg, P., Bjerkaas, M., Simonsen, T., Helgesen, C., Hjorth, N., Bach, R. & Hoff, J. 2007. Aerobic high-intensity intervals improve VO2max more than moderate training. Med Sci Sports Exerc 39, 665–671.
34. Hellsten, Y. & Nyberg, M. 2015. Cardiovascular adaptations to exercise training. Compr Physiol 6, 1–32.
35. Hickson, R.C., Bomze, H.A. & Holloszy, J.O. 1977. Linear increase in aerobic power induced by a strenuous program of endurance exercise. J Appl Physiol 42, 372–376.
36. Hijazi, O.M., Ramanathan, M., Estrera, A.S., Peshock, R.M. & Hsia, C.C. 1998. Fixed maximal stroke index in patients after pneumonectomy. Am J Respir Crit Care Med 157, 1623–1629.
37. Hill, A.V. & Lupton, H. 1923. Muscular exercise, lactic acid, and the supply and utilization of oxygen. Q J Med Jan, 135–171.
38. Hoppeler, H. & Weibel, E.R. 1998. Limits for oxygen and substrate transport in mammals. J Exp Biol 201, 1051–1064.
39. Hopper, M.K., Coggan, A.R. & Coyle, E.F. 1988. Exercise stroke volume relative to plasma-volume expansion. J Appl Physiol (1985), 64, 404–408.
40. Howden, E.J., Perhonen, M., Peshock, R.M., Zhang, R., Arbab-Zadeh, A., Adams-Huet, B. & Levine, B.D. 2015. Females have a blunted cardiovascular response to one year of intensive supervised endurance training. J Appl Physiol (1985) 119, 37–46.
41. Hu, M. & Lin, W. 2012. Effects of exercise training on red blood cell production: implications for anemia. Acta Haematol 127, 156–164.
42. Jacobs, R.A., Fluck, D., Bonne, T.C., Burgi, S., Christensen, P.M., Toigo, M. & Lundby, C. 2013. Improvements in exercise performance with high-intensity interval training coincide with an increase in skeletal muscle mitochondrial content and function. J Appl Physiol (1985) 115, 785–793.
43. Jelkmann, W. & Lundby, C. 2011. Blood doping and its detection. Blood 118, 2395–2404.
44. Joyner, M.J. & Casey, D.P. 2015. Regulation of increased blood flow (Hyperemia) to muscles during exercise: a hierarchy of competing physiological needs. Physiol Rev 95, 549–601.
45. Joyner, M.J. & Green, D.J. 2009. Exercise protects the cardiovascular system: effects beyond traditional risk factors. J Physiol 587, 5551–5558.
46. Kalliokoski, K.K., Oikonen, V., Takala, T.O., Sipila, H., Knuuti, J. & Nuutila, P. 2001. Enhanced oxygen extraction and reduced flow heterogeneity in exercising muscle in endurance-trained men. Am J Physiol Endocrinol Metab 280, E1015–E1021.
47. Kalliokoski, K.K., Knuuti, J. & Nuutila, P. 2005. Relationship between muscle blood flow and oxygen uptake during exercise in endurance-trained and untrained men. J Appl Physiol (1985) 98, 380–383.
48. Kanstrup, I.L. & Ekblom, B. 1982. Acute hypervolemia, cardiac performance, and aerobic power during exercise. J Appl Physiol Respir Environ Exerc Physiol 52, 1186–1191.
49. Keiser, S., Fluck, D., Huppin, F., Stravs, A., Hilty, M.P. & Lundby, C. 2015. Heat training increases exercise capacity in hot but not in temperate conditions: a mechanistic counter-balanced cross-over study. Am J Physiol Heart Circ Physiol 309, H750–H761.
50. Kirsch, K., Risch, W.D., Mund, U., Röcker, L. & Stosoy, H. 1975. Low pressure system and blood volume regulating hormones after prolonged exercise. In: S.B. Ag, (ed) Metabolic Adaptation to Prolonged Physical Exercise, pp. 315–321. Birkhäuser, Lausanne.
51. Kirsch, K.A., Rocker, L., von Ameln, H. & Hrynyschyn, K. 1986. The cardiac filling pressure following exercise and thermal stress. Yale J Biol Med 59, 257–265.
52. Kjellberg, S.R., Rudhe, U. & Sjostrand, T. 1949a. Increase of the amount of hemoglobin and blood volume in connection with physical training. Acta Physiol Scand 19, 146–151.
53. Kjellberg, S.R., Rudhe, U. & Sjostrand, T. 1949b. The relation of the cardiac volume to the weight and surface area of the body, the blood volume and the physical capacity for work. Acta Radiol 31, 113–122.
54. Klausen, K., Secher, N.H., Clausen, J.P., Hartling, O. & Trap-Jensen, J. 1982. Central and regional circulatory adaptations to one-leg training. Journal of Applied Physiology Respiratory Environmental and Exercise Physiology 52, 976–983.
55. Knuttgen, H.G., Nordesjö, L.O., Ollander, B. & Saltin, B. 1973. Physical conditioning through interval training with young male adults. Med Sci Sports Exerc 5, 220–226.
56. Levine, B.D. 2008. VO2max: what do we know, and what do we still need to know? J Physiol 586, 25–34.
57. Levine, B.D., Lane, L.D., Buckey, J.C., Friedman, D.B. & Blomqvist, C.G. 1991. Left ventricular pressure-volume and Frank-Starling relations in endurance athletes. Implications for orthostatic tolerance and exercise performance. Circulation 84, 1016–1023.
58. Lundby, C. & Jacobs, R.A. 2016. Adaptations of skeletal muscle mitochondria to exercise training. Exp Physiol 101, 17–22.
59. Lundby, C. & Montero, D. 2015. CrossTalk opposing view: diffusion limitation of O2 from microvessels into muscle does not contribute to the limitation of VO2 max. J Physiol 593, 3759–3761.
60. Lundby, C. & Robach, P. 2015. Performance enhancement: what are the physiological limits? Physiology (Bethesda) 30, 282–292.
61. Lundby, C., Gassmann, M. & Pilegaard, H. 2006a. Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions. Eur J Appl Physiol 96, 363–369.
62. Lundby, C., Sander, M., van Hall, G., Saltin, B. & Calbet, J.A. 2006b. Maximal exercise and muscle oxygen extraction in acclimatizing lowlanders and high altitude natives. J Physiol 573, 535–547.
63. Lundby, C., Boushel, R., Robach, P., Moller, K., Saltin, B. & Calbet, J.A. 2008. During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory level. J Physiol 586, 123–130.
64. Macpherson, R.E., Hazell, T.J., Olver, T.D., Paterson, D.H. & Lemon, P.W. 2011. Run sprint interval training improves aerobic performance but not maximal cardiac output. Med Sci Sports Exerc 43, 115–122.
65. Marshall, P., Al-Timman, J., Riley, R., Wright, J., Williams, S., Hainsworth, R. & Tan, L.B. 2001. Randomized controlled trial of home-based exercise training to evaluate cardiac functional gains. Clin Sci 101, 477–483.
66. Mezzani, A. & Guazzi, M. 2016. Balancing the evidence on the cardiovascular determinants of oxygen uptake improvement after endurance training in the elderly: What are the next steps? Eur J Prev Cardiol 23, 730–732.
67. Montero, D. & Díaz-Cañestro, C. 2016. Endurance training and maximal oxygen consumption with ageing: role of maximal cardiac output and oxygen extraction. Eur J Prev Cardiol 23, 733–743.
68. Montero, D., Cathomen, A., Jacobs, R.A., Flück, D., de Leur, J., Keiser, S., Bonne, T., Kirk, N., Lundby, A.-K. & Lundby, C. 2015a. Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training. J Physiol 593, 4677–4688.
69. Montero, D., Díaz-Cañestro, C. & Lundby, C. 2015b. Endurance training and V O2max: role of maximal cardiac output and oxygen extraction. Med Sci Sports Exerc 47, 2024–2033.
70. Montero, D., Rauber, S., Goetze, J.P. & Lundby, C. 2016. Reduction in central venous pressure enhances erythropoietin synthesis: role of volume-regulating hormones. Acta Physiol (Oxf) 218, 89–97.
71. Morris, N., Gass, G., Thompson, M., Bennett, G., Basic, D. & Morton, H. 2002. Rate and amplitude of adaptation to intermittent and continuous exercise in older men. Med Sci Sports Exerc 34, 471–477.
72. Mundry, R. & Nunn, C.L. 2009. Stepwise model fitting and statistical inference: turning noise into signal pollution. Am Nat 173, 119–123.
73. Murias, J.M., Kowalchuk, J.M. & Paterson, D.H. 2010a. Mechanisms for increases in V O2max with endurance training in older and young women. Med Sci Sports Exerc 42, 1891–1898.
74. Murias, J.M., Kowalchuk, J.M. & Paterson, D.H. 2010b. Time course and mechanisms of adaptations in cardiorespiratory fitness with endurance training in older and young men. J Appl Physiol (1985), 108, 621–627.
75. Nordesjö, L.O. 1974. The effect of quantitated training on the capacity for short and prolonged work. Acta Physiol Scand Suppl 405, 1–54.
76. Panebianco, R.A., Stachenfeld, N., Coplan, N.L. & Gleim, G.W. 1995. Effects of blood donation on exercise performance in competitive cyclists. Am Heart J 130, 838–840.
77. Pedersen, B.K. & Saltin, B. 2015. Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports 25, 1–72.
78. Prud'homme, D., Bouchard, C., Leblanc, C., Landry, F. & Fontaine, E. 1984. Sensitivity of maximal aerobic power to training is genotype-dependent. Med Sci Sports Exerc 16, 489–493.
79. Rankinen, T., Wolfarth, B., Simoneau, J.-A., Maier-Lenz, D., Rauramaa, R., Rivera, M.A., Boulay, M.R., Chagnon, Y.C., Pérusse, L., Keul, J. & Bouchard, C. 2000. No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status. J Appl Physiol (1985) 88, 1571–1575.
80. Rankinen, T., Fuku, N., Wolfarth, B., Wang, G., Sarzynski, M.A., Alexeev, D.G., Ahmetov, I.I., Boulay, M.R., Cieszczyk, P., Eynon, N. et al. 2016. No evidence of a common DNA variant profile specific to world class endurance athletes. PLoS ONE 11, e0147330.
81. Robach, P., Boisson, R.C., Vincent, L., Lundby, C., Moutereau, S., Gergele, L., Michel, N., Duthil, E., Feasson, L. & Millet, G.Y. 2014. Hemolysis induced by an extreme mountain ultra-marathon is not associated with a decrease in total red blood cell volume. Scand J Med Sci Sports 24, 18–27.
82. Robinson, S., Edwards, H.T. & Dill, D.B. 1937. New records in human power. Science 85, 409–410.
83. Roecker, L., Kowoll, R., Fraszl, W., Battal, K., Brechtel, L., Brachmann, S., Meier-Buttermilch, R., Gunga, H.C., Stangl, A. & Kiesewetter, H. 2006. Observation of serum erythropoietin concentrations in female athletes for up to eight days after a marathon run. Clin Lab 52, 511–513.
84. Ross, R., de Lannoy, L. & Stotz, P.J. 2015. Separate effects of intensity and amount of exercise on interindividual cardiorespiratory fitness response. Mayo Clin Proc 90, 1506–1514.
85. Rud, B., Foss, O., Krustrup, P., Secher, N.H. & Hallen, J. 2012. One-legged endurance training: leg blood flow and oxygen extraction during cycling exercise. Acta Physiol (Oxf) 205, 177–185.
86. Rundqvist, H., Rullman, E., Sundberg, C.J., Fischer, H., Eisleitner, K., Stahlberg, M., Sundblad, P., Jansson, E. & Gustafsson, T. 2009. Activation of the erythropoietin receptor in human skeletal muscle. Eur J Endocrinol 161, 427–434.
87. Saltin, B., Blomqvist, G., Mitchell, J.H., Johnson, R.L. Jr, Wildenthal, K. & Chapman, C.B. 1968. Response to exercise after bed rest and after training. Circulation 38, VII1–VII78.
88. Sarzynski, M.A., Ghosh, S. & Bouchard, C. 2016. Genomic and transcriptomic predictors of response levels to endurance exercise training. J Physiol. doi: 10.1113/JP272559.
89. Sawka, M.N., Convertino, V.A., Eichner, E.R., Schnieder, S.M. & Young, A.J. 2000. Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness. Med Sci Sports Exerc 32, 332–348.
90. Schmidt, W. & Prommer, N. 2008. Effects of various training modalities on blood volume. Scand J Med Sci Sports 18(Suppl 1), 57–69.
91. Schmidt, W., Eckardt, K.U., Hilgendorf, A., Strauch, S. & Bauer, C. 1991. Effects of maximal and submaximal exercise under normoxic and hypoxic conditions on serum erythropoietin level. Int J Sports Med 12, 457–461.
92. Schwandt, H.J., Heyduck, B., Gunga, H.C. & Rocker, L. 1991. Influence of prolonged physical exercise on the erythropoietin concentration in blood. Eur J Appl Physiol Occup Physiol 63, 463–466.
93. Shields, R. 2011. Common disease: are causative alleles common or rare? PLoS Biol 9, e1001009.
94. Simonson, T.S. 2015. Altitude adaptation: a glimpse through various lenses. High Alt Med Biol 16, 125–137.
95. Skinner, J.S., Jaskólski, A., Jaskólska, A., Krasnoff, J., Gagnon, J., Leon, A.S., Rao, D.C., Wilmore, J.H. & Bouchard, C. 2001. Age, sex, race, initial fitness, and response to training: the HERITAGE Family Study. J Appl Physiol (1985) 90, 1770–1776.
96. Spence, A.L., Naylor, L.H., Carter, H.H., Buck, C.L., Dembo, L., Murray, C.P., Watson, P., Oxborough, D., George, K.P. & Green, D.J. 2011. A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans. J Physiol 589, 5443–5452.
97. Spina, R.J., Ogawa, T., Martin, W.H., Coggan, A.R., Holloszy, J.O. & Ehsani, A.A. 1992. Exercise training prevents decline in stroke volume during exercise in young healthy-subjects. J Appl Physiol 72, 2458–2462.
98. Spina, R.J., Ogawa, T., Kohrt, W.M., Martin, W.H. 3rd, Holloszy, J.O. & Ehsani, A.A. 1993a. Differences in cardiovascular adaptations to endurance exercise training between older men and women. J Appl Physiol (1985) 75, 849–855.
99. Spina, R.J., Ogawa, T., Miller, T.R., Kohrt, W.M. & Ehsani, A.A. 1993b. Effect of exercise training on left ventricular performance in older women free of cardiopulmonary disease. Am J Cardiol 71, 99–104.
100. Spina, R.J., Turner, M.J. & Ehsani, A.A. 1998. beta-adrenergic-mediated improvement in left ventricular function by exercise training in older men. American Journal of Physiology-Heart and Circulatory Physiology 274, H397–H404.
101. Taylor, H.L., Buskirk, E. & Henschel, A. 1955. Maximal oxygen intake as an objective measure of cardio-respiratory performance. J Appl Physiol 8, 73–80.
102. Thompson, H. 2012. Performance enhancement: superhuman athletes. Nature 487, 287–289.
103. Wagner, P.D. 1992. Gas exchange and peripheral diffusion limitation. Med Sci Sports Exerc 24, 54–58.
104. Wagner, P.D. 2015. CrossTalk proposal: diffusion limitation of O2 from microvessels into muscle does contribute to the limitation of VO2 max. J Physiol 593, 3757–3758.
105. Wang, E., Næss, M.S., Hoff, J., Albert, T.L., Pham, Q., Richardson, R.S. & Helgerud, J. 2014. Exercise-training-induced changes in metabolic capacity with age: the role of central cardiovascular plasticity. Age 36, 665–676.
106. Warburton, D.E., Gledhill, N. & Quinney, H.A. 2000. Blood volume, aerobic power, and endurance performance: potential ergogenic effect of volume loading. Clin J Sport Med 10, 59–66.
107. Warburton, D.E., Haykowsky, M.J., Quinney, H.A., Blackmore, D., Teo, K.K., Taylor, D.A., McGavock, J. & Humen, D.P. 2004. Blood volume expansion and cardiorespiratory function: effects of training modality. Med Sci Sports Exerc 36, 991–1000.
108. Weight, L.M., Alexander, D., Elliot, T. & Jacobs, P. 1992. Erythropoietic adaptations to endurance training. Eur J Appl Physiol Occup Physiol 64, 444–448.
109. Weiss, K.M. 2008. Tilting at Quixotic Trait Loci (QTL): an evolutionary perspective on genetic causation. Genetics 179, 1741–1756.
110. Weng, T.P., Huang, S.C., Chuang, Y.F. & Wang, J.S. 2013. Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men. PLoS ONE 8, e80248.