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

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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.

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Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability.

J M Guralnik, L Ferrucci, E Simonsick … (1995)

Functional assessment is an important part of the evaluation of elderly persons. We conducted this study to determine whether objective measures of physical function can predict subsequent disability in older persons. This prospective cohort study included men and women 71 years of age or older who were living in the community, who reported no disability in the activities of daily living, and who reported that they were able to walk one-half mile (0.8 km) and climb stairs without assistance. The subjects completed a short battery of physical-performance tests and participated in a follow-up interview four years later. The tests included an assessment of standing balance, a timed 8-ft (2.4-m) walk at a normal pace, and a timed test of five repetitions of rising from a chair and sitting down. Among the 1122 subjects who were not disabled at base line and who participated in the four-year follow-up, lower scores on the base-line performance tests were associated with a statistically significant, graduated increase in the frequency of disability in the activities of daily living and mobility-related disability at follow-up. After adjustment for age, sex, and the presence of chronic disease, those with the lowest scores on the performance tests were 4.2 to 4.9 times as likely to have disability at four years as those with the highest performance scores, and those with intermediate performance scores were 1.6 to 1.8 times as likely to have disability. Among nondisabled older persons living in the community, objective measures of lower-extremity function were highly predictive of subsequent disability. Measures of physical performance may identify older persons with a preclinical stage of disability who may benefit from interventions to prevent the development of frank disability.

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Epidemiology of sarcopenia among the elderly in New Mexico.

R. Paul Ross, Markus Baumgartner, L. Romero … (1998)

Muscle mass decreases with age, leading to "sarcopenia," or low relative muscle mass, in elderly people. Sarcopenia is believed to be associated with metabolic, physiologic, and functional impairments and disability. Methods of estimating the prevalence of sarcopenia and its associated risks in elderly populations are lacking. Data from a population-based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico (the New Mexico Elder Health Survey, 1993-1995) were analyzed to develop a method for estimating the prevalence of sarcopenia. An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a random subsample (n = 199) of participants and was extended to the total sample. Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 (m2) being less than two standard deviations below the mean of a young reference group. Prevalences increased from 13-24% in persons under 70 years of age to >50% in persons over 80 years of age, and were slightly greater in Hispanics than in non-Hispanic whites. Sarcopenia was significantly associated with self-reported physical disability in both men and women, independent of ethnicity, age, morbidity, obesity, income, and health behaviors. This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia.

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A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women.

W. R. Frontera, V. A. Hughes, K. J. Lutz … (1991)

The isokinetic strength of the elbow and knee extensors and flexors was measured in 200 healthy 45- to 78-yr-old men and women to examine the relationship between muscle strength, age, and body composition. Peak torque was measured at 60 and 240 degrees/s in the knee and at 60 and 180 degrees/s in the elbow by use of a Cybex II isokinetic dynamometer. Fat-free mass (FFM) was estimated by hydrostatic weighing in all subjects, and muscle mass (MM) was determined in 141 subjects from urinary creatinine excretion. FFM and MM were significantly lower (P less than 0.001) in the oldest group. Strength of all muscle groups at both testing speeds was significantly (P less than 0.006) lower (range 15.5-26.7%) in the 65- to 78- than in the 45- to 54-yr-old men and women. When strength was adjusted for FFM or MM, the age-related differences were not significant in all muscle groups except the knee extensors tested at 240 degrees/s. Absolute strength of the women ranged from 42.2 to 62.8% that of men. When strength was expressed per kilogram of MM, these gender differences were smaller and/or not present. These data suggest that MM is a major determinant of the age- and gender-related differences in skeletal muscle strength. Furthermore, this finding is, to a large extent, independent of muscle location (upper vs. lower extremities) and function (extension vs. flexion).

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Author and article information

Contributors

: +33-5-61145628 , +33-5-61145640 , macesari@gmail.com

: roger.fielding@tufts.edu

Journal

Journal ID (nlm-ta): J Cachexia Sarcopenia Muscle

Journal ID (iso-abbrev): J Cachexia Sarcopenia Muscle

Title: Journal of Cachexia, Sarcopenia and Muscle

Publisher: Springer-Verlag (Berlin/Heidelberg )

ISSN (Print): 2190-5991

ISSN (Electronic): 2190-6009

Publication date (Electronic): 3 August 2012

Publication date PMC-release: 3 August 2012

Publication date (Print): September 2012

Volume: 3

Issue: 3

Pages: 181-190

Affiliations

[ ]Gerontopôle and INSERM Unit 1027, Université de Toulouse, Toulouse, France

[ ]Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, 02111 Boston, MA USA

[ ]Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL USA

[ ]Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA USA

[ ]Department of Nutritional Sciences and Toxicology, University of California at Berkeley, San Francisco, CA USA

[ ]Department of Cardiology, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany

[ ]Centre for Clinical and Basic Research, IRCCS San Raffaele, Rome, Italy

[ ]Harvard Medical School, Boston, MA USA

[ ]Neurotune AG, Schlieren, Switzerland

[ ]Human Medicine Special Areas, Scientific Advice Section, European Medicines Agency, London, UK

[ ]Institut Mérieux, Lyon, France

[ ]Départment de kinanthropologie, Université du Quebec, Montreal, Canada

[ ]Clinical Research Operations, Neuroscience & Neuromuscular Disorders, Cytokinetics Inc., South San Francisco, CA USA

[ ]Department of Medicine, University of Verona, Verona, Italy

[ ]Institute for Biomedicine of Aging, Friedrich-Alexander-University Erlangen-Nürnberg, Nuremberg, Germany

[ ]Novartis Institutes for Biomedical Research, Basel, Switzerland

[ ]Muscle Metabolism DPU, Metabolic Pathways CEDD, GlaxoSmithKline, Research Triangle Park, NC USA

[ ]Musculoskeletal Translational Medicine, Novartis Institutes for Biomedical Research, Cambridge, MA USA

[ ]University School of Medicine and GRECC, VA Medical Center, St. Louis, MO USA

[ ]Institut du Vieillissement, Gerontopôle, Université de Toulouse, 37 Allées Jules Guesde, 31000 Toulouse, France

Article

Publisher ID: 78

DOI: 10.1007/s13539-012-0078-2

PMC ID: 3424187

PubMed ID: 22865205

SO-VID: 4d4e6da5-d03e-410c-919e-f27e763a9a7e

History

Date received : 23 May 2012

Date accepted : 11 June 2012

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

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Most cited references 50

Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability.

Epidemiology of sarcopenia among the elderly in New Mexico.

A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women.

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