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Research

SOLUBLE BIOCHEMICAL MARKERS OF SARCOPENIA: WHERE ARE WE NOW AND WHERE DO WE NEED TO GO?

The 27th Annual Meeting of the European Orthopaedic Research Society (EORS), Maastricht, The Netherlands, 2–4 October 2019.



Abstract

Sarcopenia is a progressive and generalized skeletal muscle disorder that involves loss of muscle mass and function. It is associated with increased adverse outcomes including falls, functional decline, frailty and mortality and affects 65% of people over the age of 65 more than half of people aged 80 and above. The factors that cause and worsen sarcopenia are categorised into two groups. The primary aetiological factor is ageing and the secondary factors include disease, physical inactivity, and poor nutrition. Sarcopenia is considered to be ‘primary' (or age-related) when no other specific cause is evident. However, a number of ‘secondary' factors may be present in addition to ageing. Sarcopenia can occur secondary to a systemic or inflammatory disease, including malignancy and organ failure. Physical inactivity is one of the major contributors to the development of sarcopenia, whether due to a sedentary lifestyle or to disease related immobility or disability. Furthermore, sarcopenia can develop as a result of inadequate protein consumption. Biomarkers are objective and quantifiable characteristics of physiological and pathophysiological processes. Biomarkers can be used to predict the development of sarcopenia in older susceptible adults and enable early interventions that can reduce the risk of physical disability, the co-morbidities associated with the loss of muscle mass and the poor health outcomes that result from sarcopenia. Non-invasive imaging technologies can be used as biomarkers to detect loss of skeletal muscle mass in sarcopenia include bone densitometry, computed tomography, ultrasound and magnetic resonance imaging. However, imaging requires sophisticated and expensive equipment that is not available in a resource poor setting. Therefore, markers of skeletal muscle strength and fitness and soluble biochemical markers in blood may be used as alternative biomarkers. Studies on sarcopenia have identified numerous soluble biochemical biomarkers. These biomarkers can be divided into two groups: “muscle-specific” and “non-muscle-specific” biomarkers. Since sarcopenia is associated with rapid skeletal muscle wasting, the skeletal muscle-specific isoform of troponin T may be considerate a useful biomarker of sarcopenia, since high troponin levels in blood are an expression of muscle wasting. Peptides derived from collagen type VI turnover may be potential biomarkers of sarcopenia. We have recently conducted a systematic review to summarize the data from recent mass-spectrometry based proteomic studies of the secretome of skeletal muscle cells in response to disease, exercise or metabolic stress in order to identify the proteins involved in muscle breakdown. Developing robust in vitro models for the study of sarcopenia using primary muscle cells is a high priority as is exploiting the in vitro models to understand catabolic and inflammatory processes and molecular mechanisms involved in sarcopenia. Co-cultures with adipose-derived and other cells may be used to screen for small molecules and biologicals capable of inhibiting the catabolic and inflammatory pathways involved in sarcopenia. This presentation reviews recent progress in this area and outlines opportunities for future research on sarcopenia.


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