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Adaptations to the neuromuscular system are marked by aging and are evidenced by direct quantification of MUs from human cadavers or indirectly by estimating MU numbers via electrophysiological techniques.

Early postmortem work shows a substantial reduction in the number of motor neurons (around 30–50%) in the lumber spine of older (>60 years) compared with younger adults [3]. Around the same time, two more cadaver studies demonstrated a decrease in motor neurons serving muscle fibers in the lower spinal region [4, 5]. Myoelectrical examination of various anatomical muscles have added to this body of knowledge. The estimated number of MU in the tibialis anterior, a key dorsiflexor, progressively decreases from young (~25 years [150 MUs]) to old (~65 years [91 MUs]) men, and further declines in the oldest men (~85 years [59 MUs]) [6]. Numerous other studies corroborate this loss of MU in upper (biceps brachii) [7] and lower limb (vastus lateralis) [8] muscles when comparing older adults with their younger counterparts. Although MU numbers have been reported with clear differences between young and old, MU number estimate techniques are limited by muscle size and electrode detection area, likely explaining the remarkably similar MU numbers reported for muscles of vastly different sizes (e.g. 138 in the first dorsal interosseous [9] and 195 in the VL [8]). Therefore, these methods should be viewed as an index rather than a true anatomical count.

A recent review of the literature also noted that by the seventh decade of life, healthy older adults have around 40% fewer MUs [10] than young. Of note, these studies have been conducted in healthy older adults, which demonstrates that neuromuscular remodeling is, to some degree, an unavoidable physiological consequence of aging. A recent review [11] further discusses the neuromuscular adaptions that occur even in states of healthy aging.

Until recently, the direct role of MU remodeling in the pathophysiology of sarcopenia was unknown. Although findings from immunosenescent studies of animal models showed that apoptosis of motor neurons and subsequent denervation of muscle fibers leads to muscle weakness in diseases which overlap with sarcopenia [12]. Compelling work by Piasecki and colleagues [13] was the first to quantify MUs across healthy young, non‐sarcopenic old, pre‐sarcopenic older, and sarcopenic older men. Unsurprisingly, muscle mass (8, 30, 44%), MU number (33, 47, 50%), and maximal strength (34, 39, 49%) were significantly lower in non‐sarcopenic old, pre‐sarcopenic older, and sarcopenic older men, respectively, in comparison with the younger reference group [12]. Moreover, MU potentials recorded with intramuscular needle electrodes were larger by 26 and 41% in non‐sarcopenia and pre‐sarcopenic older men, respectively, and were similar to young in the sarcopenic older men. Taken together this suggests “healthier” older men can reinnervate larger bundles of muscle fibers to counteract the loss of motor neurons with age, but this process may fail and contribute to the sarcopenic condition via muscle fiber loss [13]. This phenomenon, known as the denervation–reinnervation cycle, or MU remodeling (Figure 4.1), is a likely explanation for the increased size of MU observed in upper‐and lower‐limb locomotory muscles [15–19] of previous studies in older adults. Others have also noted that the remaining MUs in an aged muscle are enlarged by around 50% [10]. Indeed, this MU remodeling process is thought to preferentially affect fast‐twitch fibers, which via compensatory mechanisms are reinnervated by the smaller earlier recruited MU, or undergo apoptosis [11]. This may result in two scenarios, (i) the smaller MUs adopt control of the muscle resulting in conversion to a “slower” phenotype or (ii) there is a reduction of muscle fibers in a single MU, both of which may reduce force output required to perform activities of daily living (ADL) (Figure 4.1). More recent work among 86 older men demonstrated that a greater MU potential size of the vastus lateralis muscle was associated with a reduced risk of frailty (β = −0.10, 95% CI: −0.18, −0.02, p = 0.013 [adjusted for age and body mass index]) when utilizing the frailty index as a diagnostic tool [20]. These finding are of particular relevance given both sarcopenia and frailty share overlapping characteristics, with the former condition also a risk factor for the latter [21].

Figure 4.1 Motor unit remodeling and the denervation–reinnervation phenomenon.

Source: Wilkinson and colleagues [14].