SLOWING DOWN AGE-RELATED MUSCLE LOSS AND SARCOPENIA
P. NOIREZ 12 AND G. BUTLER-BROWNE 1
1. WHAT IS A SKELETAL MUSCLE 1 Muscle fibres
CHAPTER 5
SLOWING DOWN AGE-RELATED MUSCLE LOSS
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1.2 Each muscle is unique
Most correlative morphological and functional studies on human muscle have been performed on the large thigh muscle, the vastus lateralis. The results from these studies have provided us with golden standards for human muscle morphology and function. It has become increasingly evident that each human muscle is unique with respect to its muscle fibre composition, fibre diameter and function (Stal et al.,1994). The smallest natural unit of muscular contraction is called the motor unit: it corresponds to a set of muscle fibres which are innervated by the same motoneuron. Human skeletal muscle display three main types of motor unit: the IIx motor units which are fast and fatigable, the IIa motor units which are fast but resistant to fatigue, and the I motor units which are slowly contracting and resistant to fatigue. In general, the slow motor units are the smallest. Motor unit recruitment varies according to physical effort such that an increased production of force requires not only the recruitment of motor units from the smallest to the largest, but also increasingly smaller time lapses between recruitment. In humans, all the fibres that make up a motor unit have identical characteristics. The muscle fibres of slow motor units are termed type I fibres, contain slow twitch MyHC.
Human fast motor units are composed of type II fibres and subgroups thereof (IIA and IIX). They contain different fast isoforms of MyHC, are fast contracting and, depending on the subtype, show various degrees of resistance to fatigue. Some small hand muscles like the interossei have a mixed composition of fibre types and are of large diameters, whereas the lumbricale muscles are almost exclusively composed of type I fibres (Stal et al., 1994; Soukup et al., 2003). The muscle fibre composition in the trapezius muscle differs in the different parts of the muscle and there are obvious differences related to gender (Lindman et al.,1991).
Some facial muscles have small sized fibres which contain mainly fast myosin isoforms (Stal et al., 1994) whereas the masticatory muscles are very complex and have fibres which contain mixtures of different myosin isoforms, some of which are not present in limb muscles such as alpha cardiac and fetal myosin (Butler-Browne et al., 1988; Pedrosa-Domellof et al., 1992). These observations suggest that the muscles may also behave differently upon aging and to some extent this is what has been observed. The age related changes in the masseter, a jaw closing muscle, and the lateral pterygoid, a jaw stabilizing muscle, are opposite to those reported for limb and trunk muscles. On the contrary, changes in the anterior and posterior bellies of the digastricus, a jaw opening muscle, resemble those of limb and trunk muscles (Thornell et al.,2003). The individual variability seems also to be large and there is still no consensus on the effects of aging on the vastus lateralis. Some studies have reported an increase in the relative percentage of type I fibres, others a decrease, and a further subset observe no change in fiber proportions (Thornell et al.,2003). Therefore, the heterogeneity and individual variability in the structure and function of the different human muscles should be kept in mind when discussing the different aspects of sarcopenia and its prevention.
SLOWING DOWN AGE-RELATED MUSCLE LOSS AND SARCOPENIA 73 1.3 Muscular lesion
Muscles are continually undergoing adaptation to different function needs as well as injury. Injury caused by elongation or contusion of the muscle, represents over 90% of muscle injuries. This type of injury occurs when excessive force is applied to the muscle resulting in over-stretching. More often than not, these lesions are located near the neuromuscular junction of superficial muscles working on two joints, such as the femoris rectus of the quadriceps. A slight lesion corresponds to the tearing of a few muscle fibres, which results in slight discomfort (the twinge scenario) with little or no loss of force or restriction of movement. A moderate lesion corresponds to more significant damage with a decrease in force production.
With a severe lesion, the tearing of the muscle affects the whole or part of the muscle, leading to total loss of muscle function (Jarvinen et al., 2005). Luckily, striated skeletal muscle has an incredible capacity for regenerating itself. Even in the absence of severe tearing, the muscle can also suffer a relative degree of damage or remodelling after a mere session of physical exercise (Yu et al., 2004). Even those who practice sport at a high level are not exempt from these micro-lesions of the muscle. They are particularly frequent in physical or sports activities that require the production of maximum force or eccentric muscle contractions. Aching muscle pain (or DOMS syndrome – Delayed Onset Muscle Soreness), representing a pain peak 48 hours after exercise (Cheung et al.,2003), is the soreness that may result either from the degeneration and regeneration phenomena taking place in the damaged muscle or to the remodelling (Yu et al.,2004).
1.4 Muscle Satellite Cells
There exists a particularly interesting cell population situated on the edge of the muscle fibres wich are called satellite or myosatellite cells: these cells are quiescent myoblasts that reside adjacent to the muscle fibre sarcolemma and beneath the basement lamina. Myoblast is a term designating a myogenic cell that is fully determined with respect to its myogenic phenotype. Early during development, multinucleated myotubes are formed by proliferating myoblasts, which withdraw from the cell cycle and fuse with one another. Myoblasts continue to be added to these myotubes allowing them to expand in both length and girth to become mature muscle fibres (Edom et al.,1994). Thus during development and postnatal growth, nuclei are added to the muscle fibres by the fusion of myoblasts to the parent fibre.
The identification of satellite cells in 1961 (Mauro,1961) led to a rapid progress in our understanding of the early events involved in skeletal muscle regeneration. If the quiescent state of satellite cells were a delicate equilibrium between electrical activity, growth factors and extra-cellular matrix composition, disequilibrium of the environment would trigger activation and proliferation of satellite cells. Following a muscle trauma, the satellite cells proliferate and either form new muscle fibres or repair damaged fibres via a process equivalent to muscle histogenesis (Bischoff and Heintz,1994). In recent years, the importance of satellite cells has been emphasized
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by the discovery that their proliferation is evoked not only by acute muscle injury but also by muscle overuse and increased muscle tension. A number of factors are involved in this regulation of satellite cell activation (Hawke and Garry,2001).