Motor unit firing rates in young and very old adult males during an isokinetic fatiguing task and short-term recovery in the anconeus muscle.

Understanding motor unit (MU) properties with muscle fatigue in adult aging is limited to isometric tasks. The purpose was to investigate the effect of an isokinetic fatiguing task on MU firing rates between two adult age groups of males. Single MUs were recorded by intramuscular electrodes in the anconeus muscle of eight young (19-33 yr) and 11 very old adults (78-93 yr). Fatigue was induced by repeated isokinetic maximal voluntary contractions at 25% of maximum velocity (Vmax), until elbow extension power decreased by 35%. At baseline, the very old had lower maximal power (135 vs. 214 W, P = 0.002) and slower maximal velocity (177 vs. 196°/s, P < 0.001) compared with young. Despite a similar number of contractions (average 39 young and 44 very old) to task failure (P = 0.33), the older males were less fatigable as time under tension was ∼25% longer (P = 0.04). Maximum firing rates from ∼20 single MUs per age group were tracked continuously throughout the task and during 10 min of recovery. Similar rates were recorded (24.7 and 23.6 Hz, P = 0.18) at baseline 25% Vmax, and during the task (23.3 and 28.7% decrease, P = 0.21) between young and very old, respectively. Power and MU rates were recovered similarly by 2 min of rest in both groups (all P > 0.15). Despite differences in baseline capability, very old males in this relatively slow isokinetic task were more fatigue resistant, but the fatigue-related reduction and recovery in MU rates were similar between groups. Therefore, fatigue in this task between age groups is not differentially affected by alterations in firing rates.NEW & NOTEWORTHY Maximal motor unit firing rates were recorded during an isokinetic fatiguing protocol and short-term recovery in young and very old adult males. Prior studies were limited to isometric fatiguing tasks. Despite the old being ∼37% weaker and less fatigable, anconeus rates during elbow extension declined with fatigue and recovered similarly to young males. Therefore, it is unlikely that greater fatigue resistance of very old males during isokinetic contractions is related to differences in motor unit rates.

Length-dependent changes of lower limb muscle morphology in Chronic Inflammatory Demyelinating Polyneuropathy assessed with magnetic resonance imaging.

The objective of the present study was to assess muscle quantity of the thigh and leg in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) compared to age and sex matched controls in exploring length-dependent changes of innervated muscles. In five people with CIDP and seven controls, magnetic resonance imaging was used to assess muscle morphology of the four parts of the quadriceps and medial hamstring muscles. Findings were compared to the triceps surae from a subset of participants. The CIDP group had less contractile tissue in the quadriceps (11.5%, P<0.05), hamstrings (15.6%, P<0.05) and triceps surae (35.9%, P<0.05) compared to controls. Additionally, CIDP had less contractile tissue (18.7%) in the triceps surae compared to the hamstrings (P<0.05). Muscle quantity in the quadriceps and hamstrings in CIDP was less than controls, but differences were greater for the distal triceps surae. These findings support a length-dependent affect of CIDP on limb musculature composition.

Anconeus motor unit firing rates during isometric and muscle-shortening contractions comparing young and very old adults.

With effects of aging, voluntary neural drive to the muscle, measured as motor unit (MU) firing rate, is lower in older adults during sustained isometric contractions compared with young adults, but differences remain unknown during limb movements. Therefore, our purpose was to compare MU firing rates during both isometric and shortening contractions between two adult age groups. We analyzed intramuscular electromyography of single-MU recordings in the anconeus muscle of young (n = 8, 19-33 yr) and very old (n = 13, 78-93 yr) male adults during maximal voluntary contractions (MVCs). In sustained isometric and muscle-shortening contractions during limb movement, MU trains were linked with elbow joint kinematic parameters throughout the contraction time course. The older group was 33% weaker and 10% slower during movements than the young group (P < 0.01). In isometric contractions, median firing rates were 42% lower (P < 0.01) in the older group (18 Hz) compared with the young group (31 Hz), but during shortening contractions firing rates were higher for both age groups and not statistically different between groups. As a function of contraction time, firing rates at MU recruitment threshold were 39% lower in the older group, but the firing rate decrease was attenuated threefold throughout shortening contraction compared with the young group. At the single-MU level, age-related differences during isometric contractions (i.e., pre-movement initiation) do not remain constant throughout movement that comprises greater effects of muscle shortening. Results indicate that neural drive is task dependent and during movement in older adults it is decreased minimally.NEW & NOTEWORTHY Changes of neural drive to the muscle with adult aging, measured as motor unit firing rates during limb movements, are unknown. Throughout maximal voluntary efforts we found that, in comparison with young adults, firing rates were lower during isometric contraction in older adults but not different during elbow extension movements. Despite the older group being ∼33% weaker across contractions, their muscles can receive neural drive during movements that are similar to that of younger adults.

Neuroprotective effects of exercise on the aging human neuromuscular system.

Human biological aging from maturity to senescence is associated with a gradual loss of muscle mass and neuromuscular function. It is not until very old age (>80 years) however, that these changes often manifest into functional impairments. A driving factor underlying the age-related loss of muscle mass and function is the reduction in the number and quality of motor units (MUs). A MU consists of a single motoneuron, located either in the spinal cord or the brain stem, and all of the muscle fibres it innervates via its peripheral axon. Throughout the adult lifespan, MUs are slowly, but progressively lost. The compensatory process of collateral reinnervation attempts to recapture orphaned muscle fibres following the death of a motoneuron. Whereas this process helps mitigate loss of muscle mass during the latter decades of adult aging, the neuromuscular system has fewer and larger MUs, which have lower quality connections between the axon terminal and innervated muscle fibres. Whether this process of MU death and degradation can be attenuated with habitual physical activity has been a challenging question of great interest. This review focuses on age-related alterations of the human neuromuscular system, with an emphasis on the MU, and presents findings on the potential protective effects of lifelong physical activity. Although there is some discrepancy across studies of masters athletes, if one considers all experimental limitations as well as the available literature in animals, there is compelling evidence of a protective effect of chronic physical training on human MUs. Our tenet is that high-levels of physical activity can mitigate the natural trajectory of loss of quantity and quality of MUs in old age.

Obstruction of Small Arterioles in Patients with Critical Limb Ischemia due to Partial Endothelial-to-Mesenchymal Transition.

Critical limb ischemia (CLI) is a hazardous manifestation of atherosclerosis and treatment failure is common. Abnormalities in the arterioles might underlie this failure but the cellular pathobiology of microvessels in CLI is poorly understood. We analyzed 349 intramuscular arterioles in lower limb specimens from individuals with and without CLI. Arteriolar densities were 1.8-fold higher in CLI muscles. However, 33% of small (<20 µm) arterioles were stenotic and 9% were completely occluded. The lumens were closed by bulky, re-oriented endothelial cells expressing abundant N-cadherin that uniquely localized between adjacent and opposing endothelial cells. S100A4 and SNAIL1 were also expressed, supporting an endothelial-to-mesenchymal transition. SMAD2/3 was activated in occlusive endothelial cells and TGFß1 was increased in the adjacent mural cells. These findings identify a microvascular closure process based on mesenchymal transitions in a hyper-TGFß environment that may, in part, explain the limited success of peripheral artery revascularization procedures.

Abnormal motor unit firing rates in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: Patients with CIDP have impairments, including muscle weakness, that could be consequences of demyelination, conduction block, and eventually axonal loss and denervation, leading to muscle atrophy. Consequently, motor unit (MU) activation of the muscle may be impaired contributing to weakness; but this has not been explored in CIDP. METHODS: MU firing rates were recorded at four levels of voluntary isometric dorsiflexion contractions (25%, 50%, 75% and 100% of maximal voluntary contraction [MVC]) in 8 (6 male, 2 female) patients with CIDP and 7 (4 male, 3 female) controls. RESULTS: Patients with CIDP were 33% weaker. The mean MU firing rates of the CIDP group were ~ 19 Hz at 25%, ~16 Hz at 50% MVC, ~18 Hz at 75% MVC and ~ 17 Hz at 100% MVC. The controls had rates of ~13 Hz at 25%, ~18 Hz at 50% MVC, ~32 Hz at 75% MVC and ~ 40 Hz at 100% MVC. Surface root mean squared electromyography normalized to the MVC was less in patients with CIDP at 50 and 75% MVC. CONCLUSIONS: As a consequence secondary to MU loss, patients with CIDP demonstrate significantly lower mean firing rates at high contraction intensities, and higher mean firing rates at low contraction intensities.

Nerve dysfunction leads to muscle morphological abnormalities in chronic inflammatory demyelinating polyneuropathy assessed by MRI.

Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n = 10) of CIDP patients compared with a healthy age-matched control group (n = 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413-420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77-84, 2019. © 2019 Wiley Periodicals, Inc.

Human motor unit characteristics of the superior trapezius muscle with age-related comparisons.

Current understanding of human motor unit (MU) control and aging is mostly derived from hand and limb muscles that have spinal motor neuron innervations. The aim here was to characterize and test whether a muscle with a shared innervation supply from brainstem and spinal MU populations would demonstrate similar age-related adaptations as those reported for other muscles. In humans, the superior trapezius (ST) muscle acts to elevate and stabilize the scapula and has primary efferent supply from the spinal accessory nerve (cranial nerve XI) located in the brainstem. We compared electrophysiological properties obtained from intramuscular and surface recordings between 10 young (22-33 yr) and 10 old (77-88 yr) men at a range of voluntary isometric contraction intensities (from 15 to 100% of maximal efforts). The old group was 41% weaker with 43% lower MU discharge frequencies compared with the young (47.2 ± 9.6 Hz young and 26.7 ± 5.8 Hz old, P < 0.05) during maximal efforts. There was no difference in MU number estimation between age groups (228 ± 105 young and 209 ± 89 old, P = 0.33). Furthermore, there were no differences in needle detected near fiber (NF) stability parameters of jitter or jiggle. The old group had lower amplitude and smaller area of the stimulated compound muscle action potential and smaller NF MU potential area with higher NF counts. Thus, despite age-related ST weakness and lower MU discharge rates, there was minimal evidence of MU loss or compensatory reinnervation.NEW & NOTEWORTHY The human superior trapezius (ST) has shared spinal and brainstem motor neuron innervation providing a unique model to explore the impact of aging on motor unit (MU) properties. Although the ST showed higher MU discharge rates compared with most spinally innervated muscles, voluntary strength and mean MU rates were lower in old compared with young at all contraction intensities. There was no age-related difference in MU number estimates with minimal electrophysiological evidence of collateral reinnervation.

Reductions in muscle quality and quantity in chronic inflammatory demyelinating polyneuropathy patients assessed by magnetic resonance imaging.

INTRODUCTION: Weakness in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) may be caused by decreases in muscle quantity and quality, but this has not been explored. METHODS: Twelve patients with CIDP (mean age 61 years) and 10 age-matched (mean age 59 years) control subjects were assessed for ankle dorsiflexion strength, and two different MRI scans (T1 and T2) of leg musculature. RESULTS: Isometric strength was 36% lower in CIDP patients compared with controls. Tibialis anterior muscle volumes of CIDP patients were smaller by ∼17% compared with controls, and non-contractile tissue volume was ∼58% greater in CIDP patients. When normalized to total muscle or corrected contractile volume, strength was ∼29% and ∼18% lower, respectively, in CIDP patients. DISCUSSION: These results provide insight into the structural integrity of muscle contractile proteins and pathologic changes to whole-muscle tissue composition that contribute to impaired muscle function in CIDP. Muscle Nerve 58: 396-401, 2018.

Neuromuscular changes of the aged human hamstrings.

Despite the life-long importance for posture and locomotion, neuromuscular properties of the hamstrings muscle have not been explored with adult aging. The purpose of this study was to assess and compare age-related effects on contractile function, spinal motor neuron output expressed as motor unit (MU) discharge rates in the hamstrings of 11 young (26 ± 4 yr) and 10 old (80 ± 5 yr) men. Maximal voluntary isometric contractions (MVC), stimulated contractile properties, and surface and intramuscular electromyography (EMG) from submaximal to MVC were recorded in the biceps femoris (BF) and semimembranosus-semitendinosus (SS) muscles. MVC torque was ~50% less in the old with both age groups attaining ≥93% mean voluntary activation. Evoked twitches in the old were ~50% lower in amplitude and >150% longer in duration compared with those in the young. At successive voluntary contractions of 25, 50, and 100% MVC, MU discharge rates were up to 45% lower in old, with no differences in relative submaximal surface EMG between age groups. Furthermore, the old had significantly lower MU discharge rates in the SS at all contraction intensities compared with the BF muscle. Men in their 8th to 10th decades of life demonstrate substantially lower strength and MU discharge rates in this functionally important large lower limb muscle group, with greater age-related effect on discharge rates in the medial hamstrings. These findings, compared with those in other muscles studied, highlight that the neuromuscular properties of limb muscles, and indeed within functionally similar portions of a muscle group, are not all affected equally by the aging process. NEW & NOTEWORTHY In the hamstrings, we found that both contractile function and motor unit discharge rates across the range of voluntary intensities were lower in the old. The differences in discharge rates due to age were greater in the medial hamstrings muscle group compared with the lateral hamstrings. Compared with previous studies, these results highlight that not all muscles are affected equally by aging and there may be compartmental differences within functionally similar muscles.

Effect of very old age on anconeus motor unit loss and compensatory remodelling.

INTRODUCTION: It is not known how the process of compensatory remodeling through collateral reinnervation continues into very old age (>80 years) or whether there is a limit to effective motor unit (MU) reinnervation. Therefore, we explore electrophysiological properties related to motor unit number estimates (MUNEs) in very old participants (79-90 years of age) compared with young controls (25-29 years of age). METHODS: Decomposition-enhanced spike-triggered averaging was used to collect surface and intramuscular electromyography information from the anconeus to derive a MUNE. RESULTS: Young participants had a MUNE of ∼38 and ∼25 at 30% and 50% root mean squared maximum voluntary contraction (RMSMVC ) with surface motor unit potentials (S-MUPs) of ∼145 µV and 236 µV, respectively. Older participants had a MUNE of ∼23 and ∼16 at 30% and 50% RMSMVC with S-MUPs of 168 µV and 232 µV, respectively. DISCUSSION: In this muscle, an age limit to successful remodeling through collateral reinnervation, to compensate for the presumed ongoing losses of MUs, may have been surpassed. Muscle Nerve 57: 659-663, 2018.

Maintaining Motor Units into Old Age: Running the Final Common Pathway.

Invited Letter to the Editor. This article is a commentary on the recently published manuscript "Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen". Mosole S, Carraro U, Kern H, Loefler S, Zampieri S. Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen. Eur J Transl Myol 2016;26:5972. doi: 10.4081/ejtm.2016.5972. We offer some unique perspectives on masters athletes and the role of physical activity in maintaining the number and function of motor units into old age.

Motor unit number estimation and neuromuscular fidelity in 3 stages of sarcopenia.

INTRODUCTION: Loss of motor units (MUs) and alterations in MU properties are major factors in development of sarcopenia. The purpose of this study was to compare MU properties among 3 groups categorized as either pre-sarcopenic (n = 7), sarcopenic (n = 7), or severely sarcopenic (n = 5), all with similarly aged subjects (75-82 years). METHODS: Using decomposition-enhanced quantitative electromyography, MU number estimates and neuromuscular stability measures of near-fiber (NF) jitter and jiggle were derived in addition to contractile properties of ankle dorsiflexors. RESULTS: MU number estimates were similar across groups; however, maximal voluntary strength in the severe sarcopenia group was 27% and 37% less than the sarcopenic and pre-sarcopenic groups, respectively. Moreover, NF jiggle was 31% greater in the severe group compared with pre-sarcopenia, NF jitter was 43% greater in the severe group compared with the pre-sarcopenic group. CONCLUSION: Unlike MU number estimates, strength and MU stability differed across groups and related to degree of sarcopenia. Muscle Nerve 55: 676-684, 2017.

Electrophysiological and neuromuscular stability of persons with chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: We assessed motor unit (MU) properties and neuromuscular stability in the tibialis anterior (TA) of chronic inflammatory demyelinating polyneuropathy (CIDP) patients using decomposition-based quantitative electromyography. METHODS: Dorsiflexion strength was assessed, and surface and concentric needle electromyography were sampled from the TA. Estimates of MU numbers were derived using decomposition-based quantitative electromyography and spike-triggered averaging. Neuromuscular transmission stability was assessed from concentric needle-detected MU potentials. RESULTS: CIDP patients had 43% lower compound muscle action potential amplitude than controls, and despite near-maximum voluntary activation, were 37% weaker. CIDP had 27% fewer functioning MUs in the TA, and had 90% and 44% higher jiggle and jitter values, respectively compared with controls. CONCLUSIONS: CIDP had lower strength and compound muscle action potential values, moderately fewer numbers of MUs, and significant neuromuscular instability compared with controls. Thus, in addition to muscle atrophy, voluntary weakness is also due to limitations of peripheral neural transmission consistent with demyelination. Muscle Nerve 56: 413-420, 2017.

Neuromuscular function in different stages of sarcopenia.

This study applied the screening tool developed by the European Working Group on Sarcopenia in Older People (EWGSOP) on seniors aged over 65years and concurrently tested various laboratory-based indices of neuromuscular function. Twenty-four healthy and independent living older adults (9 men, 15 women) with a mean age of 79.1±5.8years participated. Based on gait speed, handgrip strength and muscle mass all subjects were categorized into one of the three conceptual sarcopenia stages (pre-sarcopenia, sarcopenia, severe sarcopenia). Maximal strength of dorsiflexors in the left leg was measured and voluntary activation was assessed by the interpolated twitch technique. In addition, isometric evoked contractile properties were recorded. Skeletal muscle mass was assessed by ultrasound from nine sites. There were roughly equal number of subjects in each sarcopenic category, and age was not different among the 3 groups. There were no differences in handgrip strength and skeletal muscle mass index among the 3 groups. Gait speed was significantly slower (p<0.01) in the severe sarcopenic subjects compared to the pre-sarcopenic group. With no differences in voluntary activation among the groups, the maximal voluntary contractions (MVCs) for severe sarcopenic subjects were 29% lower (p=0.02) and with 19% slower (p=0.02) voluntary rates of torque development (RTD) compared to sarcopenic subjects. Furthermore, the severe group was 34% lower (p=0.04) with 36% slower (p=0.02) RTD compared to pre-sarcopenic subjects. Peak twitch tension was 54% lower (p<0.01) in the severe group compared with the pre-sarcopenic group. Maximal twitch RTD were 40% (p=0.03) slower for the severe group compared to the sarcopenia group, and 51% slower (p=0.03) compared with the pre-sarcopenia group, but when normalized to peak torques there were no statistical differences. The laboratory tests found neuromuscular differences among the 3 groups which generally supported the classification scheme and helped to illustrate some key factors that could explain differences in functional capacities. These initial findings support the assumption that this categorization is relevant for identifying older adults with different neuromuscular properties. However, further studies are needed to provide more insight into the specific neuromuscular changes in the three sarcopenia stages, and how these changes relate to functional capacity. Such studies could ultimately contribute to identifying optimal interventions to improve neuromuscular functioning.

Motor unit number and transmission stability in octogenarian world class athletes: Can age-related deficits be outrun?

Our group has shown a greater number of functioning motor units (MU) in a cohort of highly active older (∼65 yr) masters runners relative to age-matched controls. Because of the precipitous loss in the number of functioning MUs in the eighth and ninth decades of life it is unknown whether older world class octogenarian masters athletes (MA) would also have greater numbers of functioning MUs compared with age-matched controls. We measured MU numbers and neuromuscular transmission stability in the tibialis anterior of world champion MAs (∼80 yr) and compared the values with healthy age-matched controls (∼80 yr). Decomposition-enhanced spike-triggered averaging was used to collect surface and intramuscular electromyography signals during dorsiflexion at ∼25% of maximum voluntary isometric contraction. Near fiber (NF) MU potential analysis was used to assess neuromuscular transmission stability. For the MAs compared with age-matched controls, the amount of excitable muscle mass (compound muscle action potential) was 14% greater (P < 0.05), there was a trend (P = 0.07) toward a 27% smaller surface-detected MU potential representative of less collateral reinnervation, and 28% more functioning MUs (P < 0.05). Additionally, the MAs had greater MU neuromuscular stability than the controls, as indicated by lower NF jitter and jiggle values (P < 0.05). These results demonstrate that high-performing octogenarians better maintain neuromuscular stability of the MU and mitigate the loss of MUs associated with aging well into the later decades of life during which time the loss of muscle mass and strength becomes functionally relevant. Future studies may identify the concomitant roles genetics and exercise play in neuroprotection.

Superantigens subvert the neutrophil response to promote abscess formation and enhance Staphylococcus aureus survival in vivo.

Staphylococcus aureus is a versatile bacterial pathogen that produces T cell-activating toxins known as superantigens (SAgs). Although excessive immune activation by SAgs can induce a dysregulated cytokine storm as a component of what is known as toxic shock syndrome (TSS), the contribution of SAgs to the staphylococcal infection process is not well defined. Here, we evaluated the role of the bacterial superantigen staphylococcal enterotoxin A (SEA) in a bacteremia model using humanized transgenic mice expressing SAg-responsive HLA-DR4 molecules. Infection with S. aureus Newman induced SEA-dependent Vß skewing of T cells and enhanced bacterial survival in the liver compared with infection by sea knockout strain. SEA-induced gamma interferon, interleukin-12, and chemokine responses resulted in increased infiltration of CD11b(+) Ly6G(+) neutrophils into the liver, promoting the formation of abscesses that contained large numbers of viable staphylococci. Hepatic abscesses occurred significantly more frequently in S. aureus Newman-infected livers than in livers infected with the Newman sea knockout strain, promoting the survival of S. aureus in vivo. This represents a novel mechanism during infection whereby S. aureus utilizes SAgs to form a specialized niche and manipulate the immune system.