Date Published: March 11, 2013
Publisher: Oxford University Press
Author(s): Avan Aihie Sayer, Sian M. Robinson, Harnish P. Patel, Tea Shavlakadze, Cyrus Cooper, Miranda D. Grounds.
Sarcopenia is the age-related loss of skeletal muscle mass and function. It is now recognised as a major clinical problem for older people and research in the area is expanding exponentially. One of the most important recent developments has been convergence in the operational definition of sarcopenia combining measures of muscle mass and strength or physical performance. This has been accompanied by considerable progress in understanding of pathogenesis from animal models of sarcopenia. Well-described risk factors include age, gender and levels of physical activity and this knowledge is now being translated into effective management strategies including resistance exercise with recent interest in the additional role of nutritional intervention. Sarcopenia is currently a major focus for drug discovery and development although there remains debate about the best primary outcome measure for trials, and various promising avenues to date have proved unsatisfactory. The concept of ‘new tricks for old drugs’ is, however, promising, for example, there is some evidence that the angiotensin-converting enzyme inhibitors may improve physical performance. Future directions will include a deeper understanding of the molecular and cellular mechanisms of sarcopenia and the application of a lifecourse approach to understanding aetiology as well as to informing the optimal timing of interventions.
Sarcopenia, the age-related loss of skeletal muscle mass and function, is coming of age. It is now recognised as a major clinical problem for older people and research in the area is expanding exponentially . This interest stems from the fact that sarcopenia is both common and associated with serious health consequences in terms of frailty, disability, morbidity and mortality. The estimated direct healthcare cost attributable to sarcopenia in the USA in 2000 was £18.5 bn . Furthermore, sarcopenia is associated with major co-morbidity such as obesity, osteoporosis and type 2 diabetes . But perhaps the most powerful indication that the loss of skeletal muscle, in particular strength, is important comes from the evidence that it predicts future mortality in middle-aged as well as older adults .
Skeletal muscle comprises primarily two main types of muscle fibre (myofibre): type 1 myofibres have a slow contraction time, utilise oxidative pathways and resist fatigue. In contrast, type 2 myofibres have a quick contraction time, rely on glycolytic pathways and fatigue more easily. The age-related loss of human skeletal muscle mass is due to a decrease in myofibre size and number with the loss of both fast and slow type myofibres, although the loss of fast myofibres tends to start earlier, at ∼70 years . Many factors influence the decrease in muscle mass. A significant contributor is an anabolic resistance of older skeletal muscle to protein nutrition  as seen during immobilisation  which can be ameliorated at least in part by resistance exercise and dietary supplementation . Other intensive areas of research are related to the loss of innervation  and oxidative damage . Loss of myofibre innervation is a characteristic of ageing muscles with changes occurring at many levels, from the central and peripheral nervous system to cells in skeletal muscle tissue. These include the loss of motoneurons in the central nervous system (CNS), diminished function of the remaining motoneurons, demyelination of axons and withdrawal of nerve terminals from the neuromuscular junctions (NMJs) [12, 14, 15].
The European Working Group on Sarcopenia in Older People (EWGSOP) have recently developed a practical clinical definition as well as consensus criteria for sarcopenia allowing an important step forward in the field in terms of standardising diagnosis . The recommendation is to use the presence of both low muscle mass and low muscle function (strength or performance) as summarised in an algorithm (Figure 2). The approach applies these characteristics to further define conceptual stages as presarcopenia, sarcopenia and severe sarcopenia.
Figure 2.EWGSOP-suggested algorithm for sarcopenia case finding in older individuals .
There is considerable interest in the role of lifestyle and diet in the aetiology of sarcopenia, and the extent to which interventions to change behaviour could make useful contributions to its management .
A deeper understanding of the molecular and cellular mechanisms of sarcopenia, derived from both human and animal studies, has great potential to identify novel targets for drug and other treatment strategies as well as to develop better biomarkers to monitor the efficacy of various interventions. Another exciting new area is the application of a lifecourse approach to the understanding and management of sarcopenia. This approach recognises that muscle mass and function in later life reflect not only the rate of muscle loss, but also the peak attained earlier in life (Figure 3) . Therefore, in addition to identifying the determinants of skeletal muscle loss, there needs to be focus on the factors associated with peak muscle mass and strength such as birth weight  and early nutrition  as well as the mechanisms underlying these associations . Importantly, the lifecourse approach suggests that there is potential for prevention and intervention at earlier stages of life rather than just when sarcopenia has become established although to date the evidence is scanty. This is a fertile area for future research.
Figure 3.A lifecourse approach to sarcopenia .