The increasing number and overall percentage of the elderly population, and the social and economic consequences of this increase, underline the importance of understanding neuromotor performance in elderly people. The mechanisms underlying these changes are complex (Stackhouse et al., 2001), but alterations in the components of the motor units play a central role. By the age of 80, 40–50% of muscle strength, muscle mass (sarcopenia), alpha motoneurons, and muscle cells are lost. In this chapter we will briefly discuss the age-associated changes in the motor unit, skeletal muscle functional properties and skeletal muscle structural characteristics (Table 2.1).

Muscle strength is an important determinant of functional capacity in older people. In general, the decline in strength starts during the third decade of life and accelerates during the sixth and seventh decades. The overall rate of decline is approximately 8–12% per decade (Schiller et al., 2000), although there is significant variation and some individuals seem to better preserve their strength over time (Hughes et al., 2001). Because of this decline in maximal force-generating capacity (strength), older people may be performing many activities while generating force closer to their maximal capacity. Under these conditions, acute or chronic diseases, hospitalization resulting from trauma or surgery, and inactivity may accelerate the decline in strength and result in disability. This concept of ‘close to maximal capacity’ is important during rehabilitation when the aim is not only to regain muscle strength but also to enhance functional reserve.

It may be possible to modify these age-related alterations with behavioral and pharmacological interventions, including exercise training, nutritional interventions and, in some cases, hormonal supplementation. Strength and power training in frail older people is accompanied by improvements in physical function (Bean et al., 2009).

Physiologically, muscle weakness may result from a decrease in the ability to activate the existing muscle mass, a reduction in the quantity of muscle tissue and therefore in the number of force-generating cross-bridges, a decrease in the force developed by each cross-bridge, or a combination of all three factors. Several studies have reported changes in neural mechanisms, including central nervous system drive, a delay in the conduction velocity of motor nerve fibers and a delay in transmission at the level of the neuromuscular junction. The ability to maximally activate the remaining motor unit pool is relatively preserved in the aged, although some reports show a significant reduction (Reid et al., 2012).

On the other hand, muscle atrophy is associated with a reduction in the number of motor neurons in the spinal cord and an incomplete reinnervation of denervated muscle cells leading to a decrease in the number and size of muscle fibers. Alterations in the proportions of motor units and myofibers of different types, particularly a decrease in the number or the relative cross-sectional area of type II fast fibers, are also noticeable. Finally, losses in the ability of the sarcoplasmic reticulum to handle calcium within the fibers, changes in the myosin molecule, an increased passive resistance of the connective tissue structures and/or a combination of factors may contribute to altered contractile behavior.

An important characteristic of neuromuscular performance is the time course of muscle actions. This characteristic can be studied in vivo with measurements of the speed of contraction of individual muscles or muscle groups and in vitro by measuring the maximal shortening velocity of single muscle fibers (Larsson & Moss, 1993). This property is important because the velocity of movement (and thus power generation) can have greater relevance than absolute muscle strength in the ability to perform a number of the activities of daily living and in fall prevention (Foldvari et al., 2000).

In the elderly, the in vivo muscle twitch (evoked by electrical stimulation) is characterized by prolonged contraction and 50% relaxation times. Thus, fused tetanic forces occur at lower stimulation frequencies, an adaptation that increases muscle efficiency. However, this adaptation also lengthens the time for muscle relaxation, thus impairing the ability to perform rapid powerful alternating movements. Human studies have shown that the time to produce the same absolute and relative forces during voluntary contractions is lengthened in the elderly and, therefore, the ability to generate explosive force (power) and to accelerate a limb is reduced (Frontera et al., 2000; Bean et al., 2009). These alterations have a negative effect on the protective reactions used before or during a fall. Several studies have shown that, in the elderly, differences in skeletal muscle power could explain more of the variability in function and disability, particularly during lower intensity tasks such as walking compared with higher intensity activities such as climbing stairs or rising from a chair.

Lower muscle mass or sarcopenia has been correlated with poor physical function. The likelihood of physical disability (measured as ability to perform activities of daily living) increases when the skeletal muscle index (SMI, determined by estimating whole body muscle mass and dividing by height in meters squared) values are lower than 5.75 kg/m² in women and 8.50 kg/m² in men (Melton et al., 2000). In that study, these cut-off points were used to determine the degree of sarcopenia.

The factors contributing to the loss of muscle mass with age seem to be a reduction in the numbers of both type I and type II muscle fibers and a decline in cross-sectional area, predominantly of type II fibers; the cross-sectional area of type I fibers seems to be well maintained. As mentioned above, the relative area (percentage of type II fibers divided by the mean fiber area of type II fibers) occupied by type II fibers is significantly reduced with age. Because of the differences in mechanical properties among muscle fiber types, the reduction in relative area of a fiber type may contribute to the changes in whole muscle contractile behavior. In addition to the loss of muscle mass, recent studies show that the quality of muscle fibers (force-generating capacity adjusted for muscle size) is impaired in older men (Frontera et al., 2008, 2012).

Age-related changes in the processes that regulate muscle protein mass contribute to sarcopenia as protein is the primary structural and functional macromolecule in muscle. Muscle protein content is determined by the balance between protein synthesis and breakdown and some studies in humans have shown that postabsorptive muscle protein synthesis declines with age. Although not all studies concur, it seems that mixed muscle and myofibrillar protein synthesis rates decline with advanced adult age (Welle et al., 1993; Toth et al., 2005) and increase in response to exercise training (Hasten et al., 2000). It is also possible that a failure to degrade damaged proteins and replacing them with newly synthesized proteins contribute to age-related decline in muscle mass and quality of muscle proteins (Irving et al., 2011).

Specific skeletal muscle proteins and groups of proteins, with important structural and functional roles, have different rates of metabolism. From both quantitative and functional perspectives, myosin heavy chain (MyHC) is the most important protein in skeletal muscle and its synthesis is reduced with age. In addition to the overall mass of MyHC protein, the type of MyHC isoforms expressed has relevance for both the metabolism and functionality of aging muscle. Because the isoforms are synthesized at different rates, a change in MyHC isoform distribution with age could contribute to altered MyHC protein synthesis rates. Additionally, a shift in MyHC isoform distribution can alter muscle performance given the different functional properties of each isoform (Hasten et al., 2000; Marx et al., 2002).

Aging is associated with increased cytokine levels/production and reduced circulating insulin-like growth factor-1 (IGF-1) concentrations. Studies in cultured myocytes and animal models have demonstrated the catabolic effects of cytokines and the anabolic effects of IGF-1 on skeletal muscle. Because aging is associated with increased levels of inflammatory markers, it is thought that immune activation may contribute to the development of sarcopenia. There is a growing body of evidence suggesting that chronic inflammation is one of the most important biological mechanisms underlying the decline in physical function that is often observed over the aging process. The plasma concentration of interleukin 6 (IL-6), a cytokine that plays a central role in inflammation, tends to increase with age and high serum levels of IL-6 predict disability in the elderly (Taaffe et al., 2000). Also, some preliminary data suggest that IL-6 is associated with accelerated sarcopenia (Taaffe et al., 2000). Resistance exercise training reduces the levels of inflammatory markers and increases muscle mass and function. IGF-1 is an important modulator of muscle mass and function across the entire lifespan and recent findings show that low plasma IGF-1 levels are associated with poor knee extensor muscle strength, slow walking speed and self-reported difficulties with mobility tasks. These findings suggest a role for IGF-1 in the causal pathway leading to disability in the elderly. IL-6 inhibits the secretion of IGF-1 and its biological activity, and higher plasma IL-6 levels and lower plasma IGF-1 levels have been associated with lower muscle strength and power (Hasten et al., 2000). Thus, the balance between the catabolic effect of cytokines and the anabolic effect of IGF-1 may play an important role in the development of sarcopenia (Barbieri et al., 2003).