We developed a structured search strategy in PubMed for publications in English using the search term “sarcopenia” in combination with one of the following keywords: “definition”, “screening”, “diagnosis”, “muscle mass”, “strength”, “frailty”, “malnutrition”, “cachexia”, “outcomes”, “disability”, “mortality”, “pathophysiology”, “life course”, “treatment”, and “exercise”. We focused on clinical trials, meta-analyses, and review articles. The search was completed on Dec 11, 2018. Only articles
SeminarSarcopenia
Introduction
Sarcopenia is a term derived from the Greek phrase poverty of flesh. It was first described in the 1980s as an age-related decline in lean body mass affecting mobility, nutritional status, and independence.1 The definition has since evolved, marked by two recent milestones. The first was the introduction of muscle function into the concept in six consensus definitions since 2010.2, 3, 4, 5, 6, 7 This new focus on muscle function, usually defined by muscle strength, muscle power, or physical performance, occurred because function was consistently shown to be a more powerful predictor of clinically relevant outcomes than muscle mass alone.8, 9, 10, 11 The second milestone was recognition of sarcopenia as an independent condition with an International Classification of Diseases-10 code in 2016.12 Yet, most clinicians remain unaware of the condition and the diagnostic tools needed to identify it.13, 14 This Seminar describes current progress and debate about the need for a consensus definition, desribes the approach to diagnosis and case finding, gives an overview of disease burden and pathophysiology, and outlines current treatment options, and future potential for prevention of the disease.
Section snippets
Definition
Sarcopenia has been defined as a progressive and generalised skeletal muscle disorder that involves the accelerated loss of muscle mass and function. Sarcopenia is associated with increased adverse outcomes including falls, functional decline, frailty, and mortality.15 When first used, the term sarcopenia referred to an age-related loss of muscle mass and function.1 However, for decades the term was used to describe muscle wasting (low muscle mass) alone without reference to function, and this
Case finding
Most cases of sarcopenia go undiagnosed. However, the condition cannot be universally screened for because screening tools are not accurate29, 30, 31, 32 and the effect of such screening on relevant outcomes is far from proven.33 Therefore, a case finding approach is recommended practice.15 This approach involves looking for sarcopenia when relevant symptoms are reported. These symptoms could include falling, weakness, slowness, self-reported muscle wasting, or difficulties carrying out daily
Diagnosis
The diagnosis of sarcopenia, by use of any definition of sarcopenia, is relatively straightforward. Diagnosis requires measurement of a combination of muscle mass, muscle strength, and physical performance (panel 1). All definitions use at least two parameters but different cutoff points lead to lack of standardisation and poor application of these definitions in clinical practice.14 The updated EWGSOP2 proposed a stepwise approach to diagnosis (figure 2). Diagnosis starts with a measure of
Differential diagnosis
The three main conditions in the differential diagnosis of sarcopenia are malnutrition, cachexia, and frailty.62, 63, 64 Malnutrition has been the focus of a global effort to reach a consensus definition, and this effort is changing understanding of both malnutrition and sarcopenia. The Global Leadership Initiative on Malnutrition has included reduced muscle mass as one of the three phenotypic criteria of malnutrition,65 and the new EWGSOP2 definition of sarcopenia has put a focus on muscle
Epidemiology
The disease burden from sarcopenia arises because it is a relatively common condition and is associated with short-term and long-term adverse effects. Estimates of disease frequency are becoming more precise with evolution of the definition. A systematic review explored the effect of definition on the prevalence of sarcopenia in populations of the older community. The review emphasised that the original 2010 EWGSOP definition resulted in one of the lowest pooled prevalence estimates (12·9% [95%
Pathophysiology
Ageing disturbs the homoeostasis of skeletal muscle, which requires balance between hypertrophy and regeneration through complex and not yet fully understood mechanisms and pathways (figure 4). Ageing appears to result in an imbalance between muscle protein anabolic and catabolic pathways, leading to overall loss of skeletal muscle. Cellular changes in sarcopenic muscle include a reduction in the size and number of myofibres, which particularly affects type II fibres. This is partly due to
Treatment: non-pharmacological approaches
Understanding the pathophysiology of sarcopenia is key to developing effective new interventions, and translational research in this area is rapidly increasing. Evidence-based clinical practice guidelines were published in 2018 and provide strong recommendations for physical activity as the primary treatment of sarcopenia.33 Evidence for the benefits of resistance exercise in improving skeletal muscle strength104 and mass105 individually is compelling, and evidence for its benefit in sarcopenia
Treatment: pharmacological approaches
No specific drugs have been approved for the treatment of sarcopenia. An umbrella review has brought together systematic reviews and meta-analyses focusing on pharmacological interventions to improve muscle mass, strength, and physical performance in older people.122 Very few studies have identified baseline sarcopenia status, so the findings could only be generalised to older people rather than to people with sarcopenia. The umbrella review identified ten pharmacological interventions: vitamin
Assessing the effect of interventions in research and clinical practice
Assessment of the effect of interventions in research and clinical practice is required to enable them to be targeted appropriately. Unfortunately, no clear consensus has yet been reached regarding which intermediate measures should be used in research settings128 or in clinical guidelines.33 In the absence of an established regulatory pathway for the development of interventions, the European Medicines Agency is using the SPRINTT trial111 to identify standard outcome measures that could be
Future directions
The prevention of sarcopenia is a major area of research activity and observational epidemiological studies have identified important risk factors such as older age and low socioeconomic status, as well as modifiable influences including low physical activity and poor diet,132 although the direct effects of alcohol consumption and cigarette smoking are not clear.133 The focus of preventive strategies to date has been to modify these risk factors in later life (in particular to increase levels
Conclusions
Sarcopenia is a progressive and generalised skeletal muscle disorder involving the accelerated loss of muscle mass and function that is associated with adverse health outcomes. Sarcopenia is increasingly recognised not only as an age-related problem, but also one associated with a range of long-term conditions. Several new consensus definitions have advanced the field over the past decade. Experimental medicine is focusing on translating our understanding of the pathophysiology of sarcopenia
Search strategy and selection criteria
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