Skip to main content
SpringerLink
Log in

International working group on Sarcopenia

  • Sarcopenia: Designing Phase IIB Trials
  • Published:
The journal of nutrition, health & aging

Abstract

Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x-ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fielding RA, Vellas B, Evans WJ et al (2011). Sarcopenia: An Undiagnosed Condition in Older Adults. Current Consensus Definintion: Prevalence, Etiology, and Consequences International Working Group on Sarcopenia. J Am Med Direct Assn: In press.

  2. Evans WJ (1995). What is Sarcopenia? J Gerontol 50A (special issue): 5–8.

    Google Scholar 

  3. Lang T, Streeper T, Cawthon P et al (2010). Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporos Int 21: 543–559.

    Article  PubMed  CAS  Google Scholar 

  4. Thomas DR (2010). Sarcopenia. Clin Geriatr Med 26: 331–346.

    Article  PubMed  Google Scholar 

  5. Jones TE, Stephenson KW, King JG et al (2009). Sarcopenia—mechanisms and treatments. J Geriatr Phys Ther 32: 83–89.

    PubMed  Google Scholar 

  6. Morley JE (2001). Anorexia, sarcopenia, and aging. Nutrition 17: 660–663.

    Article  PubMed  CAS  Google Scholar 

  7. Rolland Y, Czerwinski S, Abellan Van Kan G et al (2008). Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging 12: 433–450.

    Article  PubMed  CAS  Google Scholar 

  8. Frontera WR, Hughes VA, Fielding RA et al (2000). Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol 88: 1321–1326.

    PubMed  CAS  Google Scholar 

  9. Larsson L (1978). Morphological and functional characteristics of the aging skeletal muscle in man. Acta Physiol Scand Suppl 457(Suppl.): 1–36.

    Article  PubMed  CAS  Google Scholar 

  10. Larsson L (1983). Histochemical characteristics of human skeletal muscle during aging. Acat Physiol Scand 117: 469–471.

    Article  CAS  Google Scholar 

  11. Larsson L (1978). Morphological and functional characteristics of the ageing skeletal muscle in man. A cross-sectional study. Acta Physiol Scand Suppl 457: 1–36.

    Article  PubMed  CAS  Google Scholar 

  12. Larsson L (1983). Histochemical characteristics of human skeletal muscle during aging. Acta Physiol Scand 117: 469–471.

    Article  PubMed  CAS  Google Scholar 

  13. Lexell J, Henriksson-Larsen K, Winblad B, Sjostrom M (1983). Distribution of different fiber types in human skeletal muscles: effects of aging studied in whole muscle cross sections. Muscle and Nerve 6: 588–595.

    Article  PubMed  CAS  Google Scholar 

  14. Verdijk LB, Snijders T, Beelen M et al (2010). Characteristics of muscle fiber type are predictive of skeletal muscle mass and strength in elderly men. J Am Geriatr Soc 58: 2069–2075.

    Article  PubMed  Google Scholar 

  15. Weber J, Gillain S, Petermans J (2010). [Sarcopenia: a physical marker of frailty]. Rev Med Liege 65: 514–520.

    PubMed  CAS  Google Scholar 

  16. Welle S, Brooks AI, Delehanty JM et al (2003). Gene expression profile of aging in human muscle. Physiol Genomics 14: 149–159.

    PubMed  CAS  Google Scholar 

  17. Carey KA, Farnfield MM, Tarquinio SD, Cameron-Smith D (2007). Impaired expression of Notch signaling genes in aged human skeletal muscle. J Gerontol A Biol Sci Med Sci 62: 9–17.

    PubMed  Google Scholar 

  18. Schrager MA, Roth SM, Ferrell RE et al (2004). Insulin-like growth factor-2 genotype, fat-free mass, and muscle performance across the adult life span. J Appl Physiol 97: 2176–2183.

    Article  PubMed  CAS  Google Scholar 

  19. Chapman IM, MacIntosh CG, Morley JE, Horowitz M (2002). The anorexia of ageing. Biogerontology 3: 67–71.

    Article  PubMed  CAS  Google Scholar 

  20. Volpi E, Sheffield-Moore M, Rasmussen BB, Wolfe RR (2001). Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. JAMA 286: 1206–1212.

    Article  PubMed  CAS  Google Scholar 

  21. Katsanos CS, Kobayashi H, Sheffield-Moore M et al (2005). Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr 82: 1065–1073.

    PubMed  CAS  Google Scholar 

  22. Campbell WW, Crim MC, Dallal GE et al (1994). Increased protein requirements in elderly people: new data and retrospective reassessments. Am J Clin Nutr 60: 501–509.

    PubMed  CAS  Google Scholar 

  23. Campbell WW, Trappe TA, Wolfe RR, Evans WJ (2001). The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle. J Gerontol A Biol Sci Med Sci 56: M373–M380.

    PubMed  CAS  Google Scholar 

  24. Visser M, Deeg DJ, Lips P (2003). Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 88: 5766–5772.

    Article  PubMed  CAS  Google Scholar 

  25. Kuh D, Bassey EJ, Butterworth S et al (2005). Grip strength, postural control, and functional leg power in a representative cohort of British men and women: associations with physical activity, health status, and socioeconomic conditions. Journals of Gerontology Series A-Biological Sciences & Medical Sciences 60: 224–231.

    Google Scholar 

  26. Hughes VA, Roubenoff R, Wood M et al (2004). Anthropometric assessment of 10-y changes in body composition in the elderly. Am J Clin Nutr 80: 475–482.

    PubMed  CAS  Google Scholar 

  27. Hughes VA, Frontera WR, Roubenoff R et al (2002). Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr 76: 473–481.

    PubMed  CAS  Google Scholar 

  28. Kortebein P, Ferrando A, Lombeida J et al (2007). Effect of 10 days of bed rest on skeletal muscle in healthy older adults. Jama 297: 1772–1774.

    Article  PubMed  CAS  Google Scholar 

  29. Baumgartner RN, Waters DL, Gallagher D et al (1999). Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev 107: 123–136.

    Article  PubMed  CAS  Google Scholar 

  30. Morley JE (2003). Hormones and the aging process. J Am Geriatr Soc 51: S333–S337.

    Article  PubMed  Google Scholar 

  31. Guillet C, Boirie Y (2005). Insulin resistance: a contributing factor to age-related muscle mass loss? Diabetes Metab 31 Spec No 2: 5S20–5S26.

    Google Scholar 

  32. Park SW, Goodpaster BH, Lee JS et al (2009). Excessive Loss of Skeletal Muscle Mass in Older Adults with Type 2 Diabetes. Diabetes Care.

  33. Park SW, Goodpaster BH, Strotmeyer ES et al (2006). Decreased muscle strength and quality in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes 55: 1813–1818.

    Article  PubMed  CAS  Google Scholar 

  34. McDermott MM, Greenland P, Liu K et al (2001). Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA 286: 1599–1606.

    Article  PubMed  CAS  Google Scholar 

  35. McDermott MM, Guralnik JM, Albay M et al (2004). Impairments of muscles and nerves associated with peripheral arterial disease and their relationship with lower extremity functioning: the InCHIANTI Study. J Am Geriatr Soc 52: 405–410.

    Article  PubMed  Google Scholar 

  36. McDermott MM, Guralnik JM, Ferrucci L et al (2007). Physical activity, walking exercise, and calf skeletal muscle characteristics in patients with peripheral arterial disease. J Vasc Surg 46: 87–93.

    Article  PubMed  Google Scholar 

  37. Ferrucci L, Penninx BW, Volpato S et al (2002). Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc 50: 1947–1954.

    Article  PubMed  Google Scholar 

  38. Baumgartner RN, Koehler KM, Gallagher D et al (1998). Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 147: 755–763.

    PubMed  CAS  Google Scholar 

  39. Morley JE, Baumgartner RN, Roubenoff R et al (2001). Sarcopenia. J Lab Clin Med 137: 231–243.

    Article  PubMed  CAS  Google Scholar 

  40. Castillo EM, Goodman-Gruen D, Kritz-Silverstein D et al (2003). Sarcopenia in elderly men and women: the Rancho Bernardo study. Am J Prev Med 25: 226–231.

    Article  PubMed  Google Scholar 

  41. Gillette-Guyonnet S, Nourhashemi F, Andrieu S et al (2003). Body composition in French women 75+ years of age: the EPIDOS study. Mech Ageing Dev 124: 311–316.

    Article  PubMed  Google Scholar 

  42. Iannuzzi-Sucich M, Prestwood KM, Kenny AM (2002). Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci 57: M772–M777.

    PubMed  Google Scholar 

  43. Tanko LB, Movsesyan L, Mouritzen U et al (2002). Appendicular lean tissue mass and the prevalence of sarcopenia among healthy women. Metabolism 51: 69–74.

    Article  PubMed  CAS  Google Scholar 

  44. Melton LJ, 3rd, Khosla S, Crowson CS et al (2000). Epidemiology of sarcopenia. Journal of the American Geriatrics Society 48: 625–630.

    PubMed  Google Scholar 

  45. Rolland Y, Vellas B (2009). [Sarcopenia]. Rev Med Interne 30: 150–160.

    Article  PubMed  CAS  Google Scholar 

  46. Morley JE, Kim MJ, Haren MT et al (2005). Frailty and the aging male. Aging Male 8: 135–140.

    Article  PubMed  CAS  Google Scholar 

  47. Abellan Van Kan G, Chumlea WC, Gillette-Guyonnet S et al (2011). Clinical trials on sarcopenia - Methodological issues regarding Phase III trials. Clin Trials Geriatr Med: In press.

  48. Sakuma K, Yamaguchi A (2010). Molecular mechanisms in aging and current strategies to counteract sarcopenia. Curr Aging Sci 3: 90–101.

    Article  PubMed  CAS  Google Scholar 

  49. Park H, Park S, Shephard RJ, Aoyagi Y (2010). Yearlong physical activity and sarcopenia in older adults: the Nakanojo Study. European Journal of Applied Physiology 109: 953–961.

    Article  PubMed  Google Scholar 

  50. Hanson ED, Srivatsan SR, Agrawal S et al (2009). Effects of strength training on physical function: influence of power, strength, and body composition. J Strength Cond Res 23: 2627–2637.

    Article  PubMed  Google Scholar 

  51. Kemmler W, von Stengel S, Engelke K et al (2010). Exercise, body composition, and functional ability: a randomized controlled trial. Am J Prev Med 38: 279–287.

    Article  PubMed  Google Scholar 

  52. Phillips EM, Katula J, Miller ME et al (2010). Interruption of physical activity because of illness in the Lifestyle Interventions and Independence for Elders Pilot trial. J Aging Phys Act 18: 61–74.

    PubMed  Google Scholar 

  53. Reid KF, Callahan DM, Carabello RJ et al (2008). Lower extremity power training in elderly subjects with mobility limitations: a randomized controlled trial. Aging Clin Exp Res 20: 337–343.

    PubMed  Google Scholar 

  54. Cornish SM, Chilibeck PD (2009). Alpha-linolenic acid supplementation and resistance training in older adults. Appl Physiol Nutr Metab 34: 49–59.

    Article  PubMed  CAS  Google Scholar 

  55. Riechman SE, Andrews RD, Maclean DA, Sheather S (2007). Statins and dietary and serum cholesterol are associated with increased lean mass following resistance training. J Gerontol A Biol Sci Med Sci 62: 1164–1171.

    PubMed  Google Scholar 

  56. Solerte SB, Gazzaruso C, Bonacasa R et al (2008). Nutritional supplements with oral amino acid mixtures increases whole-body lean mass and insulin sensitivity in elderly subjects with sarcopenia. Am J Cardiol 101: 69E–77E.

    Article  PubMed  CAS  Google Scholar 

  57. Symons TB, Sheffield-Moore M, Wolfe RR, Paddon-Jones D (2009). A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects. J Am Dietet Assn 109: 1582–1586.

    Article  CAS  Google Scholar 

  58. Zak M, Swine C, Grodzicki T (2009). Combined effects of functionally-oriented exercise regimens and nutritional supplementation on both the institutionalised and free-living frail elderly (double-blind, randomised clinical trial). BMC Public Health 9: 39.

    Article  PubMed  Google Scholar 

  59. Smith GI, Atherton P, Reeds DN et al (2011). Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr 93: 402–412.

    Article  PubMed  CAS  Google Scholar 

  60. Campbell WW, Leidy HJ (2007). Dietary protein and resistance training effects on muscle and body composition in older persons. J Am Coll Nutr 26: 696S–703S.

    PubMed  CAS  Google Scholar 

  61. Atkinson RA, Srinivas-Shankar U, Roberts SA et al (2010). Effects of testosterone on skeletal muscle architecture in intermediate-frail and frail elderly men. J Gerontol A Biol Sci Med Sci 65: 1215–1219.

    Article  PubMed  Google Scholar 

  62. Kenny AM, Kleppinger A, Wang Y, Prestwood KM (2005). Effects of ultra-low-dose estrogen therapy on muscle and physical function in older women. J Am Geriatr Soc 53: 1973–1977.

    Article  PubMed  Google Scholar 

  63. Nass R, Pezzoli SS, Oliveri MC et al (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med 149: 601–611.

    PubMed  Google Scholar 

  64. Blackman MR, Sorkin JD, Munzer T et al (2002). Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. J Am Med Assn 288: 2282–2292.

    Article  CAS  Google Scholar 

  65. Giannoulis MG, Sonksen PH, Umpleby M et al (2006). The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. J Clin Endocrinol Metab 91: 477–484.

    Article  PubMed  CAS  Google Scholar 

  66. Jacobsen DE, Samson MM, Emmelot-Vonk MH, Verhaar HJ (2010). Raloxifene and body composition and muscle strength in postmenopausal women: a randomized, double-blind, placebo-controlled trial. Eur J Endocrinol 162: 371–376.

    Article  PubMed  CAS  Google Scholar 

  67. Giannoulis MG, Jackson N, Shojaee-Moradie F et al (2008). The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal muscle gene expression in healthy elderly men: a randomized controlled trial. J Clin Endocrinol Metab 93: 3066–3074.

    Article  PubMed  CAS  Google Scholar 

  68. Srinivas-Shankar U, Roberts SA, Connolly MJ et al (2010). Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 95: 639–650.

    Article  PubMed  CAS  Google Scholar 

  69. Cesari M, Pahor M (2008). Target population for clinical trials on sarcopenia. J Nutr Health Aging 12: 470–478.

    Article  PubMed  CAS  Google Scholar 

  70. Litaker MS, Barbeau P, Humphries MC, Gutin B (2003). Comparison of Hologic QDR-1000/W and 4500W DXA Scanners in 13- to 18-Year Olds. Obes Res 11: 1545–1552.

    Article  PubMed  Google Scholar 

  71. Lohman M, Tallroth K, Kettunen JA, Marttinen MT (2009). Reproducibility of dualenergy x-ray absorptiometry total and regional body composition measurements using different scanning positions and definitions of regions. Metabolism 58: 1663–1668.

    Article  PubMed  CAS  Google Scholar 

  72. Schoeller D, Tylavski F, Baer DJ et al (2005). QDR 4500A dual X-ray absorptiometer underestimates fat mass in comparison with criterion methods in adults. Am J Clin Nutr 8: 1018–1025.

    Google Scholar 

  73. Critchley M (1931). The neurology of old age. Lancet: 1221–1230.

  74. Forbes GB (1976). The Adult Decline in Lean Body Mass. Hum Biol 48: 161–171.

    PubMed  CAS  Google Scholar 

  75. Lesser GT, Kumar I, Steele JM (1963). Changes in Body Composition with Age. Ann N Y Acad Sci 110: 578–588.

    Article  PubMed  CAS  Google Scholar 

  76. Moore FD, Boyden CM (1963). Body Cell Mass and Limits of Hydration of the Fat-Free Body: Their Relation to Estimated Skeletal Weight. Ann N Y Acad Sci 110: 62–71.

    Article  PubMed  CAS  Google Scholar 

  77. Norris AH, Lundy T, Shock NW (1963). Trends in Selected Indices of Body Composition in Men between the Ages 30 and 80 Years. Ann N Y Acad Sci 110: 623–639.

    Article  PubMed  CAS  Google Scholar 

  78. Steen B, Birgitta K, Isaksson L, Isaksson B (1985). Body Composition at Age 70, 75, 79 and 81 Years: A Longitudinal Population Study. In: Chandra RK (ed). Nutrition, Immunity and Illness in the Elderly. Pergamon Press: New York, NY. pp 49–52.

    Google Scholar 

  79. Wessel JA, Ufer A, Vanhuss WD, Cederquist D (1963). Age Trends of Various Components of Body Composition and Functional Characteristics in Women Aged 20–69 Years. Ann N Y Acad Sci 110: 608–622.

    Article  PubMed  CAS  Google Scholar 

  80. Waters DL, Baumgartner RN, Garry PJ, Vellas B (2010). Advantages of dietary, exercise-related, and therapeutic interventions to prevent and treat sarcopenia in adult patients: an update. Clin Interv Aging 5: 259–270.

    Article  PubMed  CAS  Google Scholar 

  81. Chale-Rush A, Guralnik JM, Walkup MP et al (2010). Relationship between physical functioning and physical activity in the lifestyle interventions and independence for elders pilot. J Am Geriatr Soc 58: 1918–1924.

    Article  PubMed  Google Scholar 

  82. Peterson MD, Rhea MR, Sen A, Gordon PM (2010). Resistance exercise for muscular strength in older adults: a meta-analysis. Ageing Res Rev 9: 226–237.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Community Health, Lifespan Health Research Center, Wright State University Boonshoft School of Medicine, 3171 Research Blvd., Dayton, OH, 45420, USA

    WM. C. Chumlea

  2. Gerontopole, Inserm U 1027, University Paul Sabatier, Pole Geriatrie, CHU Purpan, 31300, Toulouse, France

    WM. C. Chumlea, M. Cesari & B. Vellas

  3. Muscle Metabolism DPU, GlaxoSmithKline, Mailstop N2.2204, 5 Moore Drive, Research Triangle Park, NC, 27709, USA

    W. J. Evans

  4. Clinical Research Branch, Harbor Hospital, 3001 Hanover Street, Baltimore, MD, 21225, USA

    L. Ferrucci

  5. Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St. Boston, Boston, MA, 02111, USA

    R. A. Fielding

  6. Dept of Aging & Geriatric Research, University of Florida, 1329 SW 16th street, suite 5251, Gainesville, FL, 32610-0107, USA

    M. Pahor

  7. Staff Physician, Pittsburgh Veterans Affairs Medical Center, University of Pittsburgh, Pittsburgh, USA

    S. Studenski

  8. 3471 Fifth Ave Suite 500, Pittsburgh Pa, 15213, USA

    S. Studenski

Authors
  1. WM. C. Chumlea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Cesari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. J. Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Ferrucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. A. Fielding
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Pahor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. Studenski
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B. Vellas
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

The Task Force Members

Corresponding author

Correspondence to S. Studenski.

Additional information

Task Force Members: Gabor Abellan van Kan (Toulouse, France), Sandrine Andrieu (Toulouse, France), Patricia Anthony (Vevey, Switzerland), Christian Asbrand (Frankfort, Germany), Matteo Cesari (Toulouse, France), Wm. Cameron Chumlea (Dayton, USA), Richard V Clark (Research Triangle Park, USA), William J. Evans (Research Triangle Park, USA), Gary Fanjiang (Abbott Park, USA), Luigi Ferrucci (Baltimore, USA), Roger A. Fielding (Boston, USA), Kelly Krohn (Rahway, USA), John Morley (Saint Louis, USA), Marco Pahor (Gainesville, USA), Yves Rolland (Toulouse, France), Daniel Rooks (Boston, USA), Ronenn Roubenoff (Cambridge, USA), Fariba Roughead (Minneapolis, USA), Cornel Sieber (Nurenberg, Germany), Stephanie Studenski (Pittsburg, USA), Bruno Vellas (Toulouse, France), Sjors Verlaan (Schiphol Airport, The Netherlands), Sander Wijers (Maastricht, The Netherlands)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chumlea, W.C., Cesari, M., Evans, W.J. et al. International working group on Sarcopenia. J Nutr Health Aging 15, 450–455 (2011). https://doi.org/10.1007/s12603-011-0092-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-011-0092-7

Key words

Search

Navigation