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Journal of Cachexia, Sarcopenia and Muscle

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Open Access 01-09-2012 | Original Article

Biomarkers of sarcopenia in clinical trials—recommendations from the International Working Group on Sarcopenia

Authors: Matteo Cesari, Roger A. Fielding, Marco Pahor, Bret Goodpaster, Marc Hellerstein, Gabor A. Van Kan, Stefan D. Anker, Seward Rutkove, J. Willem Vrijbloed, Maria Isaac, Yves Rolland, Christine M’Rini, Mylène Aubertin-Leheudre, Jesse M. Cedarbaum, Mauro Zamboni, Cornell C. Sieber, Didier Laurent, William J. Evans, Ronenn Roubenoff, John E. Morley, Bruno Vellas, for the International Working Group on Sarcopenia

Published in: Journal of Cachexia, Sarcopenia and Muscle | Issue 3/2012

Abstract

Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7–8, 2011 in Toulouse (France). The meeting was specifically focused at gaining knowledge on the currently available biomarkers (functional, biological, or imaging-related) that could be utilized in clinical trials of sarcopenia and considered the most reliable and promising to evaluate age-related modifications of skeletal muscle. Specific recommendations about the assessment of aging skeletal muscle in older people and the optimal methodological design of studies on sarcopenia were also discussed and finalized. Although the study of skeletal muscle decline is still in a very preliminary phase, the potential great benefits derived from a better understanding and treatment of this condition should encourage research on sarcopenia. However, the reasonable uncertainties (derived from exploring a novel field and the exponential acceleration of scientific progress) require the adoption of a cautious and comprehensive approach to the subject.

Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127:990S–1S.PubMed

Frontera WR, Hughes VA, Lutz KJ, Evans WJ. A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women. J Appl Physiol. 1991;71:644–50.PubMed

Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998;147:755–63.PubMedCrossRef

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. N Engl J Med. 1995;332:556–61.PubMedCrossRef

Chumlea WC, Cesari M, Evans WJ, Ferrucci L, Fielding RA, Pahor M, et al. Sarcopenia: designing phase IIB trials. J Nutr Health Aging. 2011;15:450–5.PubMedCrossRef

Pahor M, Cesari M. Designing phase II B trials in sarcopenia: the best target population. J Nutr Health Aging. 2011;15:725–30.PubMedCrossRef

Evans WJ. What is sarcopenia? J Gerontol A Biol Sci Med Sci. 1995;50 Spec No:5-8.

Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International Working Group on Sarcopenia. J Am Med Dir Assoc. 2011;12:249–56.PubMedCrossRef

Morley JE, Abbatecola AM, Argiles JM, Baracos V, Bauer J, Bhasin S, et al. Sarcopenia with limited mobility: an international consensus. J Am Med Dir Assoc. 2011;12:403–9.PubMedCrossRef

10.

Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39:412–23.PubMedCrossRef

11.

Muscaritoli M, Anker S, Argilés J, Aversa Z, Bauer J, Biolo G et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clinical nutrition (Edinburgh, Scotland). 2010;

12.

Group BDW. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95.CrossRef

13.

Clark BC, Manini TM. Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci. 2008;63:829–34.PubMedCrossRef

14.

Frontera WR, Reid KF, Phillips EM, Krivickas LS, Hughes VA, Roubenoff R, et al. Muscle fiber size and function in elderly humans: a longitudinal study. J Appl Physiol. 2008;105:637–42.PubMedCrossRef

15.

Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006;61:1059–64.PubMedCrossRef

16.

Hughes VA, Frontera WR, Wood M, Evans WJ, Dallal GE, Roubenoff R, et al. Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health. J Gerontol A Biol Sci Med Sci. 2001;56:B209–17.PubMedCrossRef

17.

Morse CI, Thom JM, Davis MG, Fox KR, Birch KM, Narici MV. Reduced plantarflexor specific torque in the elderly is associated with a lower activation capacity. Eur J Appl Physiol. 2004;92:219–26.PubMedCrossRef

18.

Goodpaster BH, Carlson CL, Visser M, Kelley DE, Scherzinger A, Harris TB, et al. Attenuation of skeletal muscle and strength in the elderly: the Health ABC Study. J Appl Physiol. 2001;90:2157–65.PubMed

19.

Klass M, Baudry S, Duchateau J. Age-related decline in rate of torque development is accompanied by lower maximal motor unit discharge frequency during fast contractions. J Appl Physiol. 2008;104:739–46.PubMedCrossRef

20.

Laroche DP, Knight CA, Dickie JL, Lussier M, Roy SJ. Explosive force and fractionated reaction time in elderly low- and high-active women. Med Sci Sports Exerc. 2007;39:1659–65.PubMedCrossRef

21.

Wang X, Miller GD, Messier SP, Nicklas BJ. Knee strength maintained despite loss of lean body mass during weight loss in older obese adults with knee osteoarthritis. J Gerontol A Biol Sci Med Sci. 2007;62:866–71.PubMedCrossRef

22.

Fiatarone MA, O'Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994;330:1769–75.PubMedCrossRef

23.

Reid KF, Callahan DM, Carabello RJ, Phillips EM, Frontera WR, Fielding RA. Lower extremity power training in elderly subjects with mobility limitations: a randomized controlled trial. Aging Clin Exp Res. 2008;20:337–43.PubMed

24.

Brooks SV, Faulkner JA. Skeletal muscle weakness in old age: underlying mechanisms. Med Sci Sports Exerc. 1994;26:432–9.PubMed

25.

Borkan GA, Hults DE, Gerzof SG, Robbins AH, Silbert CK. Age changes in body composition revealed by computed tomography. J Gerontol. 1983;38:673–7.PubMedCrossRef

26.

Aagaard P, Suetta C, Caserotti P, Magnusson SP, Kjaer M. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure. Scand J Med Sci Sports. 2010;20:49–64.PubMedCrossRef

27.

Lexell J. Evidence for nervous system degeneration with advancing age. J Nutr. 1997;127:1011S–3S.PubMed

28.

Kamen G, Sison SV, Du CC, Patten C. Motor unit discharge behavior in older adults during maximal-effort contractions. J Appl Physiol. 1995;79:1908–13.PubMed

29.

Clark DJ, Patten C, Reid KF, Carabello RJ, Phillips EM, Fielding RA. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults. J Gerontol A Biol Sci Med Sci. 2010;65:495–502.PubMedCrossRef

30.

Clark DJ, Patten C, Reid KF, Carabello RJ, Phillips EM, Fielding RA. Muscle performance and physical function are associated with voluntary rate of neuromuscular activation in older adults. J Gerontol A Biol Sci Med Sci. 2011;66:115–21.PubMedCrossRef

31.

Hakkinen K, Newton RU, Gordon SE, McCormick M, Volek JS, Nindl BC, et al. Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and older men. J Gerontol A Biol Sci Med Sci. 1998;53:B415–23.PubMedCrossRef

32.

Larsson L, Grimby G, Karlsson J. Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol. 1979;46:451–6.PubMed

33.

Martin JC, Farrar RP, Wagner BM, Spirduso WW. Maximal power across the lifespan. J Gerontol A Biol Sci Med Sci. 2000;55:M311–6.PubMedCrossRef

34.

Frontera WR, Suh D, Krivickas LS, Hughes VA, Goldstein R, Roubenoff R. Skeletal muscle fiber quality in older men and women. Am J Physiol Cell Physiol. 2000;279:C611–8.PubMed

35.

Pahor M, Manini T, Cesari M. Sarcopenia: clinical evaluation, biological markers and other evaluation tools. J Nutr Health Aging. 2009;13:724–8.PubMedCrossRef

36.

Newman AB, Kupelian V, Visser M, Simonsick E, Goodpaster B, Nevitt M, et al. Sarcopenia: alternative definitions and associations with lower extremity function. J Am Geriatr Soc. 2003;51:1602–9.PubMedCrossRef

37.

Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di Iorio A, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol. 2003;95:1851–60.PubMed

38.

Delmonico MJ, Harris TB, Visser M, Park SW, Conroy MB, Velasquez-Mieyer P, et al. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr. 2009;90:1579–85.PubMedCrossRef

39.

Hairi NN, Cumming RG, Naganathan V, Handelsman DJ, Le Couteur DG, Creasey H, et al. Loss of muscle strength, mass (sarcopenia), and quality (specific force) and its relationship with functional limitation and physical disability: the Concord Health and Ageing in Men Project. J Am Geriatr Soc. 2010;58:2055–62.PubMedCrossRef

40.

Newman AB, Haggerty CL, Goodpaster B, Harris T, Kritchevsky S, Nevitt M, et al. Strength and muscle quality in a well-functioning cohort of older adults: the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2003;51:323–30.PubMedCrossRef

41.

Rutkove SB. Electrical impedance myography: background, current state, and future directions. Muscle Nerve. 2009;40:936–46.PubMedCrossRef

42.

Rutkove S. Electrical impedance myography as a biomarker for ALS. Lancet Neurol. 2009;8:226. author reply 227.PubMedCrossRef

43.

Wang LL, Spieker AJ, Li J, Rutkove SB. Electrical impedance myography for monitoring motor neuron loss in the SOD1 G93A amyotrophic lateral sclerosis rat. Clin Neurophysiol. 2011

44.

Aaron R, Esper GJ, Shiffman CA, Bradonjic K, Lee KS, Rutkove SB. Effects of age on muscle as measured by electrical impedance myography. Physiol Meas. 2006;27:953–9.PubMedCrossRef

45.

Reeves ND, Maganaris CN, Narici MV. Ultrasonographic assessment of human skeletal muscle size. Eur J Appl Physiol. 2004;91:116–8.PubMedCrossRef

46.

Busch R, Kim YK, Neese RA, Schade-Serin V, Collins M, Awada M, et al. Measurement of protein turnover rates by heavy water labeling of nonessential amino acids. Biochim Biophys Acta. 2006;1760:730–44.PubMedCrossRef

47.

Price JC, Holmes WE, Li KW, Floreani NA, Neese RA, Turner SM, et al. Measurement of human plasma proteome dynamics with (2)H(2)O and liquid chromatography tandem mass spectrometry. Anal Biochem. 2012;420:73–83.PubMedCrossRef

48.

Wintrobe MM. Blood of normal men and women: erythrocyte counts, hemoglobin and volume of packed red cells of two hundred and twenty-nine individuals. Bull Johns Hopkins Hosp. 1933;53:118–30.

49.

Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A. How to decide who to treat. Best Pract Res Clin Rheumatol. 2009;23:711–26.PubMedCrossRef

50.

Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 2008;19:385–97.PubMedCrossRef

51.

Hippisley-Cox J, Coupland C. Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores. BMJ. 2009;339:b4229.PubMedCrossRef

52.

Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, et al. Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2004;59:242–8.PubMedCrossRef

53.

Schaap LA, Pluijm SM, Deeg DJ, Visser M. Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med. 2006;119:526.e9–17.CrossRef

54.

Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002;57:M326–32.PubMedCrossRef

55.

Cesari M, Penninx BW, Lauretani F, Russo CR, Carter C, Bandinelli S, et al. Hemoglobin levels and skeletal muscle: results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2004;59:249–54.PubMedCrossRef

56.

Penninx BW, Pahor M, Cesari M, Corsi AM, Woodman RC, Bandinelli S, et al. Anemia is associated with disability and decreased physical performance and muscle strength in the elderly. J Am Geriatr Soc. 2004;52:719–24.PubMedCrossRef

57.

Baumgartner RN, Koehler KM, Romero L, Garry PJ. Serum albumin is associated with skeletal muscle in elderly men and women. Am J Clin Nutr. 1996;64:552–8.PubMed

58.

Visser M, Kritchevsky SB, Newman AB, Goodpaster BH, Tylavsky FA, Nevitt MC, et al. Lower serum albumin concentration and change in muscle mass: the Health, Aging and Body Composition Study. Am J Clin Nutr. 2005;82:531–7.PubMed

59.

Proctor DN, O'Brien PC, Atkinson EJ, Nair KS. Comparison of techniques to estimate total body skeletal muscle mass in people of different age groups. Am J Physiol. 1999;277:E489–95.PubMed

60.

Valenti G, Denti L, Maggio M, Ceda G, Volpato S, Bandinelli S, et al. Effect of DHEAS on skeletal muscle over the life span: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2004;59:466–72.PubMedCrossRef

61.

Morley JE, Baumgartner RN, Roubenoff R, Mayer J, Nair KS. Sarcopenia. J Lab Clin Med. 2001;137:231–43.PubMedCrossRef

62.

Perrini S, Laviola L, Carreira MC, Cignarelli A, Natalicchio A, Giorgino F. The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J Endocrinol. 2010;205:201–10.PubMedCrossRef

63.

Ceglia L. Vitamin D and skeletal muscle tissue and function. Mol Aspects Med. 2008;29:407–14.PubMedCrossRef

64.

Mastaglia SR, Seijo M, Muzio D, Somoza J, Nunez M, Oliveri B. Effect of vitamin D nutritional status on muscle function and strength in healthy women aged over sixty-five years. J Nutr Health Aging. 2011;15:349–54.PubMedCrossRef

65.

Cesari M, Incalzi RA, Zamboni V, Pahor M. Vitamin D hormone: a multitude of actions potentially influencing the physical function decline in older persons. Geriatr Gerontol Int. 2011;11:133–42.PubMedCrossRef

66.

Dalal M, Ferrucci L, Sun K, Beck J, Fried LP, Semba RD. Elevated serum advanced glycation end products and poor grip strength in older community-dwelling women. J Gerontol A Biol Sci Med Sci. 2009;64:132–7.PubMedCrossRef

67.

Howard C, Ferrucci L, Sun K, Fried LP, Walston J, Varadhan R, et al. Oxidative protein damage is associated with poor grip strength among older women living in the community. J Appl Physiol. 2007;103:17–20.PubMedCrossRef

68.

Semba RD, Ferrucci L, Sun K, Walston J, Varadhan R, Guralnik JM, et al. Oxidative stress and severe walking disability among older women. Am J Med. 2007;120:1084–9.PubMedCrossRef

69.

Cesari M, Kritchevsky SB, Nicklas BJ, Penninx BW, Holvoet P, Koh-Banerjee P, et al. Lipoprotein peroxidation and mobility limitation: results from the Health, Aging, and Body Composition Study. Arch Intern Med. 2005;165:2148–54.PubMedCrossRef

70.

Semba RD, Blaum C, Guralnik JM, Moncrief DT, Ricks MO, Fried LP. Carotenoid and vitamin E status are associated with indicators of sarcopenia among older women living in the community. Aging Clin Exp Res. 2003;15:482–7.PubMed

71.

Semba RD, Lauretani F, Ferrucci L. Carotenoids as protection against sarcopenia in older adults. Arch Biochem Biophys. 2007;458:141–5.PubMedCrossRef

72.

Bhasin S, He EJ, Kawakubo M, Schroeder ET, Yarasheski K, Opiteck GJ, et al. N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone. J Clin Endocrinol Metab. 2009;94:4224–33.PubMedCrossRef

73.

Chen F, Lam R, Shaywitz D, Hendrickson RC, Opiteck GJ, Wishengrad D, et al. Evaluation of early biomarkers of muscle anabolic response to testosterone. J Cachex Sarcopenia Muscle. 2011;2:45–56.CrossRef

74.

Bolliger MF, Zurlinden A, Luscher D, Butikofer L, Shakhova O, Francolini M, et al. Specific proteolytic cleavage of agrin regulates maturation of the neuromuscular junction. J Cell Sci. 2010;123:3944–55.PubMedCrossRef

75.

Butikofer L, Zurlinden A, Bolliger MF, Kunz B, Sonderegger P. Destabilization of the neuromuscular junction by proteolytic cleavage of agrin results in precocious sarcopenia. FASEB J. 2011;25:4378–93.PubMedCrossRef

76.

Rolland Y, Lauwers-Cances V, Cristini C, Abellan van Kan G, Janssen I, Morley JE, et al. Difficulties with physical function associated with obesity, sarcopenia, and sarcopenic-obesity in community-dwelling elderly women: the EPIDOS (EPIDemiologie de l'OSteoporose) Study. Am J Clin Nutr. 2009;89:1895–900.PubMedCrossRef

77.

Zamboni M, Mazzali G, Fantin F, Rossi A, Di Francesco V. Sarcopenic obesity: a new category of obesity in the elderly. Nutr Metab Cardiovasc Dis. 2008;18:388–95.PubMedCrossRef

78.

von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle. J Cachexia Sarcopenia Muscle. 2010;1:7–8.CrossRef

Title: Biomarkers of sarcopenia in clinical trials—recommendations from the International Working Group on Sarcopenia
Authors: Matteo Cesari
Roger A. Fielding
Marco Pahor
Bret Goodpaster
Marc Hellerstein
Gabor A. Van Kan
Stefan D. Anker
Seward Rutkove
J. Willem Vrijbloed
Maria Isaac
Yves Rolland
Christine M’Rini
Mylène Aubertin-Leheudre
Jesse M. Cedarbaum
Mauro Zamboni
Cornell C. Sieber
Didier Laurent
William J. Evans
Ronenn Roubenoff
John E. Morley
Bruno Vellas
for the International Working Group on Sarcopenia
Publication date: 01-09-2012
Publisher: Springer-Verlag
Published in: Journal of Cachexia, Sarcopenia and Muscle / Issue 3/2012
Print ISSN: 2190-5991
Electronic ISSN: 2190-6009
DOI: https://doi.org/10.1007/s13539-012-0078-2

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