Biomarkers for physical frailty and sarcopenia: state of the science and future developments

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Abstract

Physical frailty and sarcopenia are two common and largely overlapping geriatric conditions upstream of the disabling cascade. The lack of a unique operational definition for physical frailty and sarcopenia and the complex underlying pathophysiology make the development of biomarkers for these conditions extremely challenging. Indeed, the current definitional ambiguities of physical frailty and sarcopenia, together with their heterogeneous clinical manifestations, impact the accuracy, specificity, and sensitivity of individual biomarkers proposed so far. In this review, the current state of the art in the development of biomarkers for physical frailty and sarcopenia is presented. A novel approach for biomarker identification and validation is also introduced that moves from the ‘one fits all’ paradigm to a multivariate methodology.

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Most cited references 63

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Muscles, exercise and obesity: skeletal muscle as a secretory organ.

Bente K. Pedersen, Mark A. Febbraio (2012)

During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.

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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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Physical performance measures in the clinical setting.

Stephanie Studenski, Subashan Perera, Dennis H. Wallace … (2003)

To assess the ability of gait speed alone and a three-item lower extremity performance battery to predict 12-month rates of hospitalization, decline in health, and decline in function in primary care settings serving older adults. Prospective cohort study. Primary care programs of a Medicare health maintenance organization (HMO) and Veterans Affairs (VA) system. Four hundred eighty-seven persons aged 65 and older. Lower extremity performance Established Population for Epidemiologic Studies of the Elderly (EPESE) battery including gait speed, chair stands, and tandem balance tests; demographics; health care use; health status; functional status; probability of repeated admission scale (Pra); and primary physician's hospitalization risk estimate. Veterans had poorer health and higher use than HMO members. Gait speed alone and the EPESE battery predicted hospitalization; 41% (21/51) of slow walkers (gait speed 1.0 m/s) (P <.0001). The relationship was stronger in the HMO than in the VA. Both performance measures remained independent predictors after accounting for Pra. The EPESE battery was superior to gait speed when both Pra and primary physician's risk estimate were included. Both performance measures predicted decline in function and health status in both health systems. Performance measures, alone or in combination with self-report measures, were more able to predict outcomes than self-report alone. Gait speed and a physical performance battery are brief, quantitative estimates of future risk for hospitalization and decline in health and function in clinical populations of older adults. Physical performance measures might serve as easily accessible "vital signs" to screen older adults in clinical settings.

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Author and article information

Journal

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

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

Journal ID (publisher-id): jcsm

Title: Journal of Cachexia, Sarcopenia and Muscle

Publisher: John Wiley & Sons, Ltd (Chichester, UK )

ISSN (Print): 2190-5991

ISSN (Electronic): 2190-6009

Publication date (Print): December 2015

Publication date (Electronic): 07 July 2015

Volume: 6

Issue: 4

Pages: 278-286

Affiliations

[1 ]Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart Rome, Italy

[2 ]Department of Chemistry, “Sapienza” University of Rome Rome, Italy

[3 ]Gérontopôle, Centre Hospitalier Universitaire de Toulouse Toulouse, France

[4 ]Institut national de la santé et de la recherche médicale (UMR1027), Université de Toulouse III Paul Sabatier Toulouse, France

[5 ]Department of Innovative Clinical Trials, University Medical Center Göttingen (UMG) Göttingen, Germany

[6 ]Muscle Metabolism Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline R&D Research Triangle Park, NC, USA

Author notes

* Correspondence to: Emanuele Marzetti, Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of the Sacred Heart School of Medicine, Teaching Hospital “Agostino Gemelli”, L.go F. Vito 8, Rome 00168, Italy: Tel: +39 (06) 3015-5559, Fax: + 39 (06) 3051-911, Email: emarzetti@ 123456live.com

[†]

These two authors contributed equally to this work.

Article

DOI: 10.1002/jcsm.12051

PMC ID: 4670735

PubMed ID: 26675566

SO-VID: 224b2e0c-1187-48f3-b337-2c336baaecb5

License:

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date received : 13 January 2015

Date revision received : 10 April 2015

Date accepted : 04 May 2015

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Biomarkers for physical frailty and sarcopenia: state of the science and future developments

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Most cited references 63

Muscles, exercise and obesity: skeletal muscle as a secretory organ.

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

Physical performance measures in the clinical setting.

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