Additional Files

Rittweger, J. . (2021). What Are Good Muscle Endpoints for Translational Studies?. Translational Medicine and Exercise Prescription, 1(1), 4–12. https://doi.org/10.53941/tmep.v1i1.24

What Are Good Muscle Endpoints for Translational Studies?

Jörn Rittweger()1,2

1Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany

2Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany

© The Author


 

Abstract

Muscles matter to our health because of their size, their involvement in energy metabolism and their relevance for locomotion. Adequate selection of good endpoints is crucial for successfully designing translational studies. At least eight different muscle functions matter to health, namely the mechanical functions of exerting force, velocity, power, elastic storage and braking power, the two metabolic functions of substrate uptake (e.g. carbohydrates, lipids and amino acids) and substrate provision (e.g. lactate and amino acids) and secretory functions. However, specific endpoint tests have been validated for muscle force and power only. Walking speed and grip strength demonstrate good predictive value for hard clinical endpoints, such as disability, loss of autonomy and death. Vertical jump power also has good ecological validity and construct validity, and it depicts excellent test-retest reliability, which is an important advantage with regard to the study of power. Assessment of muscle mass, e.g. by magnetic resonance imaging, dual energy X-ray absorptiometry or bioelectrical impedance, should be considered as an important secondary endpoint to enhance construct validity. Further secondary endpoints should be included wherever they are likely to enhance the plausibility of the study outcome and assessment of test-retest reliability at baseline is always recommended. Well-established methods exist for three relevant muscular endpoints, namely power, strength and muscle mass, and these endpoints lend themselves to utilization in clinical studies. However, such validated methods lack a number of additional muscle functions that are scientifically only emerging. This applies foremost to the metabolic function of muscles but also to its role in storage and dissipation of mechanical energy.

sarcopenia frailty musculature immobilization health

References

  1. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. New Engl J Med 1995, 332: 556. https://doi.org/10.1056/NEJM199503023320902
  2. Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, Brach J, Chandler J, Cawthon P, Connor EB, Nevitt M, Visser M, Kritchevsky S, Badinelli S, Harris T, Newman AB, Cauley J, Ferrucci L, Guralnik J. Gait speed and survival in older adults. JAMA 2011, 305: 50-58. https://doi.org/10.1001/jama.2010.1923
  3. Kruizinga MD, Stuurman FE, Groeneveld GJ, Cohen AF. The future of clinical trial design: the transition from hard endpoints to value-based endpoints. In: JE Barrett, CP Page and MC Michel (eds.), Concepts and Principles of Pharmacology: 100 Years of the Handbook of Experimental Pharmacology. Cham, Switzerland: Springer International Publishing. 2019. https://doi.org/10.1007/164_2019_302
  4. Lai AKM, Biewener AA, Wakeling JM. Muscle-specific indices to characterise the functional behaviour of human lower-limb muscles during locomotion. J Biomech 2019, 89: 134-38. https://doi.org/10.1016/j.jbiomech.2019.04.027
  5. Pedersen BK. Muscle as a secretory organ. Compr Physiol 2013, 3: 1337-62. https://doi.org/10.1002/cphy.c120033
  6. Pensini M, Martin A, Maffiuletti NA. Central versus peripheral adaptations following eccentric resistance training. Int J Sports Med 2002, 23: 567-74. https://doi.org/10.1055/s-2002-35558
  7. Gilliver SF, Degens H, Rittweger J, Sargeant AJ, Jones DA. Variation in the determinants of power of chemically skinned human muscle fibres. Exp Physiol 2009, 94: 1070-78. https://doi.org/10.1113/expphysiol.2009.048314
  8. Gilliver SF, Jones DA, Rittweger J, Degens H. Effects of oxidation on the power of chemically skinned rat soleus fibres. J Musculoskelet Neuronal Interact 2010, 10: 267-73
  9. Hill AV. The heat of shortening and dynamic constants of muscle. Proc Roy Soc (London) Ser B 1938, 126: 136. https://doi.org/10.1098/rspb.1938.0050
  10. Shephard RJ, Montelpare W, Plyley M, McCracken D, Goode RC. Handgrip dynamometry, Cybex measurements and lean mass as markers of the ageing of muscle function. Br J Sports Med 1991, 25: 204. https://doi.org/10.1136/bjsm.25.4.204
  11. Bassey EJ, Short AH. A new method for measuring power output in a single leg extension: feasibility, reliability and validity. Eur J Appl Physiol Occup Physiol 1990, 60: 385-90. https://doi.org/10.1007/BF00713504
  12. Davies CTM, Rennie R. Human power output. Nature 1968, 217:770. https://doi.org/10.1038/217770a0
  13. Runge M, Rittweger J, Russo CR, Schiessl H, Felsenberg D. Is muscle power output a key factor in the age-related decline in physical performance? A comparison of muscle cross section, chair-rising test and jumping power. Clin Physiol Funct Imaging 2004, 24: 335-40. https://doi.org/10.1111/j.1475-097X.2004.00567.x
  14. Rittweger J, Schiessl H, Felsenberg D, Runge M. Reproducibility of the jumping mechanography as a test of mechanical power output in physically competent adult and elderly subjects. J Am Geriatr Soc 2004, 52: 128. https://doi.org/10.1111/j.1532-5415.2004.52022.x
  15. Hong N, Siglinsky E, Krueger D, White R, Kim CO, Kim HC, Yeom Y, Binkley N, Rhee Y, Buehring B. Defining an international cut-off of two-legged countermovement jump power for sarcopenia and dysmobility syndrome. Osteoporos Int 2020. https://doi.org/10.1007/s00198-020-05591-x
  16. Tanaka H, Tarumi T, Rittweger J. Aging and physiological lessons from master athletes. Compr Physiol 2020, 10: 261-96. https://doi.org/10.1002/cphy.c180041
  17. Lambertz D, Perot C, Kaspranski R, Goubel F. Effects of long-term spaceflight on mechanical properties of muscles in humans. J Appl Physiol 2001, 90: 179-88. https://doi.org/10.1152/jappl.2001.90.1.179
  18. Kubo K, Kanehisa H, Kawakami Y, Fukunaga T. Influence of static stretching on viscoelastic properties of human tendon structures in vivo. J Appl Physiol 2001, 90: 520-27. https://doi.org/10.1152/jappl.2001.90.2.520
  19. Uusi-Rasi K, Patil R, Karinkanta S, Kannus P, Tokola K, Lamberg-Allardt C, Sievanen H. Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. JAMA Intern Med 2015, 175: 703-11. https://doi.org/10.1001/jamainternmed.2015.0225
  20. Krause PC, Choi JS, McMahon TA. The force-velocity curve in passive whole muscle is asymmetric about zero velocity. J Biomech 1995, 28: 1035. https://doi.org/10.1016/0021-9290(94)00162-W
  21. Speakman JR, Selman C. Physical activity and resting metabolic rate. Proceed Nutr Soc 2003, 62: 621-34. https://doi.org/10.1079/PNS2003282
  22. Rudwill F, O'Gorman D, Lefai E, Chery I, Zahariev A, Normand S, Pagano AF, Chopard A, Damiot A, Laurens C, Hodson L, Canet-Soulas E, Heer M, Meuthen PF, Buehlmeier J, Baecker N, Meiller L, Gauquelin-Koch G, Blanc S, Simon C, and Bergouignan A. Metabolic inflexibility is an early marker of bed-rest-induced glucose intolerance even when fat mass is stable. J Clin Endocrinol Metab 2018, 103: 1910-20. https://doi.org/10.1210/jc.2017-02267
  23. Rudrappa SS, Wilkinson DJ, Greenhaff PL, Smith K, Idris I, Atherton PJ. Human skeletal muscle disuse atrophy: effects on muscle protein synthesis, breakdown, and insulin resistance–a qualitative review. Front Physiol 2016, 7: 361. https://doi.org/10.3389/fphys.2016.00361
  24. Brooks GA. The science and translation of lactate shuttle theory. Cell Metab 2018, 27: 757-85. https://doi.org/10.1016/j.cmet.2018.03.008
  25. Neeland IJ, Hughes C, Ayers CR, Malloy CR, Jin ES. Effects of visceral adiposity on glycerol pathways in gluconeogenesis. Metabolism 2017, 67: 80-89. https://doi.org/10.1016/j.metabol.2016.11.008
  26. Steensberg A, Van Hall G, Osada T, Sacchetti M, Saltin B, Klarlund PB. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 2000, 529 Pt 1: 237. https://doi.org/10.1111/j.1469-7793.2000.00237.x
  27. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012, 481: 463-468. https://doi.org/https://doi.org/10.1038/nature10777
  28. Colaianni G, Cuscito C, Mongelli T, Pignataro P, Buccoliero C, Liu P, Lu P, Sartini L, Di Comite M, Mori G, Di Benedetto A, Brunetti G, Yuen T, Sun L, Reseland JE, Colucci S, New MI, Zaidi M, Cinti S, Grano M. The myokine irisin increases cortical bone mass. Proc Natl Acad Sci USA 2015, 112: 12157-62. https://doi.org/10.1073/pnas.1516622112
  29. Stanaway FF, Gnjidic D, Blyth FM, Le Couteur DG, Naganathan V, Waite L, Seibel MJ, Handelsman DJ, Sambrook PN, Cumming RG. How fast does the Grim Reaper walk? Receiver operating characteristics curve analysis in healthy men aged 70 and over. BMJ 2011, 343: d7679. https://doi.org/10.1136/bmj.d7679
  30. Folland JP, Mc Cauley TM, Williams AG. Allometric scaling of strength measurements to body size. Eur J Appl Physiol 2008, 102: 739-45. https://doi.org/10.1007/s00421-007-0654-x
  31. ISO. 5725-1. Accuracy (trueness and precision) of measurement methods and results–Part 1: General principles and definitions. International Standards Organization. Geneva, Switzerland. 1994
  32. Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994, 49: M85. https://doi.org/10.1093/geronj/49.2.M85
  33. Lauretani F, Ticinesi A, Gionti L, Prati B, Nouvenne A, Tana C, Meschi T, Maggio M. Short-physical performance battery (SPPB) score is associated with falls in older outpatients. Aging Clin Exp Res 2019, 31: 1435-42. https://doi.org/10.1007/s40520-018-1082-y
  34. Tager IB, Swanson A, Satariano WA. Reliability of physical performance and self-reported functional measures in an older population. J Gerontol A Biol Sci Med Sci 1998, 53: M295-300. https://doi.org/10.1093/gerona/53A.4.M295
  35. Hoeymans N, Wouters ER, Feskens EJ, van den Bos GA, Kromhout D. Reproducibility of performance-based and self-reported measures of functional status. J Gerontol A Biol Sci Med Sci 1997, 52: M363-68. https://doi.org/10.1093/gerona/52A.6.M363
  36. Balachandran A, Signorile JF. How to improve reporting of the short physical performance battery scores. J Gerontol A Biol Sci Med Sci 2015,70:1595-96. https://doi.org/10.1093/gerona/glv161
  37. Stellmann JP, Neuhaus A, Gotze N, Briken S, Lederer C, Schimpl M, Heesen C, Daumer M. Ecological validity of walking capacity tests in multiple sclerosis. PLoS ONE 2015, 10: e0123822. https://doi.org/10.1371/journal.pone.0123822
  38. Keppler AM, Nuritidinow T, Mueller A, Hoefling H, Schieker M, Clay I, Bocker W, Furmetz J. Validity of accelerometry in step detection and gait speed measurement in orthogeriatric patients. PLoS ONE 2019, 14: e0221732. https://doi.org/10.1371/journal.pone.0221732
  39. Buehring B, Krueger D, Fidler E, Gangnon R, Heiderscheit B, Binkley N. Reproducibility of jumping mechanography and traditional measures of physical and muscle function in older adults. Osteoporos Int 2015, 26: 819-25. https://doi.org/10.1007/s00198-014-2983-z
  40. Hardcastle SA, Gregson CL, Rittweger J, Crabtree N, Ward K, Tobias JH. Jump power and force have distinct associations with cortical bone parameters: findings from a population enriched by individuals with high bone mass. J Clin Endocrinol Metab 2014, 99: 266-75. https://doi.org/10.1210/jc.2013-2837
  41. Alvero Cruz JR, Brikis M, Chilibeck P, Frings-Meuthen P, Guzmán JV, Mittag U, Michely S, Mulder E, Tanaka H, Tank J, Rittweger J. Age-related decline in vertical jumping performance in masters track and field athletes: Concomitant influence of body composition. Front Physiol In press. https://doi.org/10.3389/fphys.2021.643649
  42. Foldvari M, Clark M, Laviolette LC, Bernstein MA, Kaliton D, Castaneda C, Pu CT, Hausdorff JM, Fielding RA, Singh MA. Association of muscle power with functional status in community-dwelling elderly women. J Gerontol A Biol Sci Med Sci 2000, 55: M192-99. https://doi.org/10.1093/gerona/55.4.M192
  43. Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Kritchevsky SB, Tylavsky FA, Rubin SM, Harris TB. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci 2006, 61: 72-77. https://doi.org/10.1093/gerona/61.1.72
  44. Clark BC, Manini TM. Sarcopenia≠dynapenia. J Gerontol A Biol Sci Med Sci 2008, 63: 829-34. https://doi.org/10.1093/gerona/63.8.829
  45. Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull 2010, 95: 139-59. https://doi.org/10.1093/bmb/ldq008
  46. Roubenoff R. Sarcopenia: a major modifiable cause of frailty in the elderly. J Nutr Health Aging 2000, 4: 140-42
  47. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 2010, 39: 412-23. https://doi.org/10.1093/ageing/afq034
  48. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M, Writing Group for the European Working Group on Sarcopenia in Older People. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019, 48: 16-31. https://doi.org/10.1093/ageing/afy169
  49. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28: 412-19. https://doi.org/10.1007/BF00280883