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].
LOSS OF MUSCLE FIBERS
The loss of MU largely correlates with the loss of muscle fibers in aging [22]. Autopsy work comparing the quadriceps muscle of younger and older men demonstrate a substantial reduction in the number of muscle fibers (~214 000) in the latter cohort [23]. A 12‐year longitudinal trial of older men also found a 14.7% decrease in the cross‐sectional area of the quadriceps muscle [24]. Regarding muscle fiber phenotypes, comparison of males and females between 15 and 83 years found a 25–35% loss in muscle mass with senescence [25]. Others have documented the same, by the sixth decade of life, the number of type II muscle fibers declined from ~60 to 30% in two separate studies [26, 27]. It should be noted that total muscle atrophy may not be specific to the loss of type II fibers alone; in the abovementioned longitudinal trial [24] there was a ~40–60% loss of type I fibers at age 75 compared with age 65. In saying this, the loss of type II fibers is suggested to occur at a more rapid rate, which is likely a direct consequence of the neuromuscular remodeling phenomenon.
REDUCED FIRING CAPACITY OF MUs
The firing rate of MU (measured by action potential activity) has received great attention due to the apparent high level of plasticity and number of older adults presenting with functional limitations. MU firing rates have been documented to be 30–35% less in older compared with younger adults during various sub‐ and maximal‐intensity contractions [28, 29], with a number of additional lower‐limb studies reporting reduced discharge rates in older compared with younger adults [8, 30–32]. This reduction in firing rates is thought to stem from the remodeling of MU; the loss of the larger muscle fibers which exhibit the greatest force potential and fastest discharge rates [11] and the shift toward a slower type 1 fiber phenotype, with evidence to suggest this may be sex dependent [33].
The decline in MU firing capacity can significantly impede an older adult’s ability to carry out ADL. For instance, the maximal effort required to perform chair rises (old 80%, young 42%) and ascend (old 78%, young 54%) and descend (old 88%, young 42%) stairs is markedly higher in older adults [34]. During these tasks, muscle activation of the knee extensors and flexors were 2‐ and 1.6‐fold higher in older vs younger adults, respectively [34]. Given there is an increased prevalence of hybrid fibers in the old compared with the young [35], greater denervation of MUs in sarcopenic older adults [13], as well an established link between MU remodeling and frailty [20], logic would dictate that MU firing rates would be even more compromised in sarcopenic individuals, although further studies are needed to examine this in diagnosed populations using a consensus definition.
MECHANISMS OF MU REMODELING
Role of resistance and endurance exercise in preserving MU function
Animal models have provided insights into the role of physical activity in maintaining the functioning of MUs. Older rats exposed to chronic exercise (10 months of swimming, 3 times/week) mitigated the loss of motor neurons, axon diameter, and fiber density in the gastrocnemius muscle when compared with sedentary age‐matched rats [36]. Another study in rats showed an 12.9% increase in fast fatigue‐resistant MUs after 8 weeks of endurance training (5 times/week of treadmill running) in the same muscle group as the previous study [37]. Of note, these MUs demonstrated faster twitch duration and increased ability to potentiate force after just 2 weeks of training [37]. Investigations involving spinal cord sections of aged mice revealed microglia content can be manipulated with endurance‐type exercise and prevent motor neuron loss [38]. However, how these findings translate to human neuromuscular physiology is unclear.
The only research elucidating the effects of age and exercise on the structure and function of MUs in humans has stemmed from masters athletes, who are typically described as individuals above 35 years old training and competing in intense athletic endeavors [39], although it is common to only include those aged over 60 years in this field of research. In a study from 2010 [40], the number of intact MUs in the tibialis anterior of masters runners (~65 years old) were compared with MU number (data published in 2005 [6]) in recreationally active controls (~25 years), and healthy age‐matched controls (~65 years) [40]. While MU number did not differ between the young and masters runners, there was a significant decline in the number of MUs in the old (~91 MU) compared with the masters runners (~140 MU) and younger (~150 MU) cohort [40], demonstrating a benefit of chronic exercise. However, these findings could not be repeated in a subsequent study, where the same anatomical muscle was examined for MU number using similar methods in healthy young (~ 26 years), master runners (~69 years), and older adults (71 years), and found both groups of old had fewer MUs than young, with no difference between older athletes and non‐athletes [19].
The most recent study on this subject differed from the previous two in that endurance (distance runners) and power (sprinters) trained masters athletes were included along with a larger muscle group, the vastus lateralis [18]. Again, there were no differences in the estimated number of MUs between healthy old and highly active masters athletes of either discipline. Comparisons showed MU potential size was greater in all older groups compared with young; however, this affect was augmented in both groups of masters athletes compared with the older controls. The authors suggested this benefit may be related to the ability of axonal sprouting and reinnervating of denervated fibers with advancing age [18], as previously described. This notion was further supported with recent biopsy data from older female masters athletes (~80 years) who demonstrated fewer markers of denervation and greater reinnervation capacity than age‐matched sedentary women (~77 years) [41].
While considering the dearth number of studies available, the abovementioned data suggest that regular endurance‐ or physical‐based exercise can offset some of the deleterious effects of aging on MU remodeling. Notwithstanding, further studies are needed to investigate the benefits of lifelong exercise in older adults, and particularly, the effect of exercise on rescuing MU structure and function in sarcopenic populations.
FUTURE DIRECTIONS
The loss of muscle mass with age is entirely explained by the atrophy and loss of individual muscle fibers [14], with further loss of function explained by altered neural mechanisms [42]. The evidence presented here clearly highlights the peripheral motor system as a key component of sarcopenia; however, the issue of MU plasticity in relation to muscle fiber loss is disproportionately underexplored in comparison with that of fiber atrophy; the former should be considered as an interventional target in future research, be that lifestyle, nutritional, or pharmaceutical. Moreover, the study of the combining factors of fiber loss and fiber atrophy would yield yet greater insight into total muscle loss, inclusive of the inter‐connectivity of the two processes, that is, is fiber atrophy a cause or a consequence of denervation and subsequent MU remodeling?