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

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, International Working Group on Sarcopenia, 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, International Working Group on Sarcopenia

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.

References

    1. Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127:990S–991S.
    1. 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;71:644–650.
    1. 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;147:755–763. doi: 10.1093/oxfordjournals.aje.a009520.
    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. N Engl J Med. 1995;332:556–561. doi: 10.1056/NEJM199503023320902.
    1. Chumlea WC, Cesari M, Evans WJ, Ferrucci L, Fielding RA, Pahor M, et al. Sarcopenia: designing phase IIB trials. J Nutr Health Aging. 2011;15:450–455. doi: 10.1007/s12603-011-0092-7.
    1. Pahor M, Cesari M. Designing phase II B trials in sarcopenia: the best target population. J Nutr Health Aging. 2011;15:725–730. doi: 10.1007/s12603-011-0058-9.
    1. Evans WJ. What is sarcopenia? J Gerontol A Biol Sci Med Sci. 1995;50 Spec No:5-8.
    1. 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;12:249–256. doi: 10.1016/j.jamda.2011.01.003.
    1. 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;12:403–409. doi: 10.1016/j.jamda.2011.04.014.
    1. 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;39:412–423. doi: 10.1093/ageing/afq034.
    1. 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;
    1. Group BDW. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95. doi: 10.1067/mcp.2001.113989.
    1. Clark BC, Manini TM. Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci. 2008;63:829–834. doi: 10.1093/gerona/63.8.829.
    1. 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;105:637–642. doi: 10.1152/japplphysiol.90332.2008.
    1. 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;61:1059–1064. doi: 10.1093/gerona/61.10.1059.
    1. 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–B217. doi: 10.1093/gerona/56.5.B209.
    1. 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;92:219–226. doi: 10.1007/s00421-004-1056-y.
    1. 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;90:2157–2165.
    1. 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;104:739–746. doi: 10.1152/japplphysiol.00550.2007.
    1. 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;39:1659–1665. doi: 10.1249/mss.0b013e318074ccd9.
    1. 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;62:866–871. doi: 10.1093/gerona/62.8.866.
    1. 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;330:1769–1775. doi: 10.1056/NEJM199406233302501.
    1. 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;20:337–343.
    1. Brooks SV, Faulkner JA. Skeletal muscle weakness in old age: underlying mechanisms. Med Sci Sports Exerc. 1994;26:432–439.
    1. Borkan GA, Hults DE, Gerzof SG, Robbins AH, Silbert CK. Age changes in body composition revealed by computed tomography. J Gerontol. 1983;38:673–677. doi: 10.1093/geronj/38.6.673.
    1. 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. doi: 10.1111/j.1600-0838.2009.01084.x.
    1. Lexell J. Evidence for nervous system degeneration with advancing age. J Nutr. 1997;127:1011S–1013S.
    1. Kamen G, Sison SV, Du CC, Patten C. Motor unit discharge behavior in older adults during maximal-effort contractions. J Appl Physiol. 1995;79:1908–1913.
    1. 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. doi: 10.1093/gerona/glq012.
    1. 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;66:115–121. doi: 10.1093/gerona/glq153.
    1. 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–B423. doi: 10.1093/gerona/53A.6.B415.
    1. Larsson L, Grimby G, Karlsson J. Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol. 1979;46:451–456.
    1. Martin JC, Farrar RP, Wagner BM, Spirduso WW. Maximal power across the lifespan. J Gerontol A Biol Sci Med Sci. 2000;55:M311–M316. doi: 10.1093/gerona/55.6.M311.
    1. 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–C618.
    1. Pahor M, Manini T, Cesari M. Sarcopenia: clinical evaluation, biological markers and other evaluation tools. J Nutr Health Aging. 2009;13:724–728. doi: 10.1007/s12603-009-0204-9.
    1. 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;51:1602–1609. doi: 10.1046/j.1532-5415.2003.51534.x.
    1. 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;95:1851–1860.
    1. 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;90:1579–1585. doi: 10.3945/ajcn.2009.28047.
    1. 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;58:2055–2062. doi: 10.1111/j.1532-5415.2010.03145.x.
    1. 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;51:323–330. doi: 10.1046/j.1532-5415.2003.51105.x.
    1. Rutkove SB. Electrical impedance myography: background, current state, and future directions. Muscle Nerve. 2009;40:936–946. doi: 10.1002/mus.21362.
    1. Rutkove S. Electrical impedance myography as a biomarker for ALS. Lancet Neurol. 2009;8:226. doi: 10.1016/S1474-4422(09)70030-4.
    1. 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
    1. 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;27:953–959. doi: 10.1088/0967-3334/27/10/002.
    1. Reeves ND, Maganaris CN, Narici MV. Ultrasonographic assessment of human skeletal muscle size. Eur J Appl Physiol. 2004;91:116–118. doi: 10.1007/s00421-003-0961-9.
    1. 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;1760:730–744. doi: 10.1016/j.bbagen.2005.12.023.
    1. 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. doi: 10.1016/j.ab.2011.09.007.
    1. 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;53:118–130.
    1. Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A. How to decide who to treat. Best Pract Res Clin Rheumatol. 2009;23:711–726. doi: 10.1016/j.berh.2009.09.002.
    1. 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;19:385–397. doi: 10.1007/s00198-007-0543-5.
    1. 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. doi: 10.1136/bmj.b4229.
    1. 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;59:242–248. doi: 10.1093/gerona/59.3.M242.
    1. Schaap LA, Pluijm SM, Deeg DJ, Visser M. Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med. 2006;119:526.e9–526.17. doi: 10.1016/j.amjmed.2005.10.049.
    1. 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–M332. doi: 10.1093/gerona/57.5.M326.
    1. 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;59:249–254. doi: 10.1093/gerona/59.3.M249.
    1. 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;52:719–724. doi: 10.1111/j.1532-5415.2004.52208.x.
    1. 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;64:552–558.
    1. 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;82:531–537.
    1. 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–E495.
    1. 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;59:466–472. doi: 10.1093/gerona/59.5.M466.
    1. Morley JE, Baumgartner RN, Roubenoff R, Mayer J, Nair KS. Sarcopenia. J Lab Clin Med. 2001;137:231–243. doi: 10.1067/mlc.2001.113504.
    1. 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;205:201–210. doi: 10.1677/JOE-09-0431.
    1. Ceglia L. Vitamin D and skeletal muscle tissue and function. Mol Aspects Med. 2008;29:407–414. doi: 10.1016/j.mam.2008.07.002.
    1. 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;15:349–354. doi: 10.1007/s12603-010-0287-3.
    1. 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;11:133–142. doi: 10.1111/j.1447-0594.2010.00668.x.
    1. 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;64:132–137. doi: 10.1093/gerona/gln018.
    1. 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. doi: 10.1152/japplphysiol.00133.2007.
    1. 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;120:1084–1089. doi: 10.1016/j.amjmed.2007.07.028.
    1. 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;165:2148–2154. doi: 10.1001/archinte.165.18.2148.
    1. 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;15:482–487.
    1. Semba RD, Lauretani F, Ferrucci L. Carotenoids as protection against sarcopenia in older adults. Arch Biochem Biophys. 2007;458:141–145. doi: 10.1016/j.abb.2006.11.025.
    1. 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;94:4224–4233. doi: 10.1210/jc.2009-1434.
    1. 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. doi: 10.1007/s13539-011-0021-y.
    1. 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;123:3944–3955. doi: 10.1242/jcs.072090.
    1. 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;25:4378–4393. doi: 10.1096/fj.11-191262.
    1. 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;89:1895–1900. doi: 10.3945/ajcn.2008.26950.
    1. 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;18:388–395. doi: 10.1016/j.numecd.2007.10.002.
    1. 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. doi: 10.1007/s13539-010-0003-5.

Source: PubMed

3
Tilaa