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Long-term exercise training has been considered as an effective strategy to counteract age-related hormonal declines and minimise muscle atrophy. However, human data relating circulating hormone levels with motor nerve function are scant. The aims of the study were to explore associations between circulating sex hormone levels and motor unit (MU) characteristics in older men, including masters athletes competing in endurance and power events. Forty-three older men (mean ± SD age: 69.9 ± 4.6 years) were studied based on competitive status. The serum concentrations of dehydroepiandrosterone (DHEA), total testosterone (T) and estradiol were quantified using liquid chromatography mass spectrometry. Intramuscular electromyographic signals were recorded from vastus lateralis (VL) during 25% of maximum voluntary isometric contractions and processed to extract MU firing rate (FR), and motor unit potential (MUP) features. After adjusting for athletic status, MU FR was positively associated with DHEA levels (p = 0.019). Higher testosterone and estradiol were associated with lower MUP complexity; these relationships remained significant after adjusting for athletic status (p = 0.006 and p = 0.019, respectively). Circulating DHEA was positively associated with MU firing rate in these older men. Higher testosterone levels were associated with reduced MUP complexity, indicating reduced electrophysiological temporal dispersion, which is related to decreased differences in conduction times along axonal branches and/or MU fibres. Although evident in males only, this work highlights the potential of hormone administration as a therapeutic interventional strategy specifically targeting human motor units in older age.

Contains fulltext : 283515.pdf (Publisher’s version ) (Open Access), BACKGROUND: Ion channel inhibition may offer protection against coronavirus disease 2019 (COVID-19). Inflammation and reduced platelet count occur during COVID-19 but precise quantification of risk thresholds is unclear. The Recov ery-SIRIO study aimed to assess clinical effects of amiodarone and verapamil and to relate patient phenotypes to outcomes. METHODS: RECOVERY-SIRIO is a multicenter open-label 1:1:1 investigator-initiated randomized trial with blinded event adjudication. A sample of 804 symptomatic hospitalized nonintensive-care COVID-19 patients, follow-up for 28 days was initially planned. RESULTS: The trial was stopped when a total of 215 patients had been randomized to amiodarone (n = 71), verapamil (n = 72) or standard care alone (n = 72). At 15 days, the hazard ratio (hazard ratio [HR], 95% confidence interval [CI]) for clinical improvement was 0.77 (0.52-1.14) with amiodarone and 0.97 (0.81-1.17) with verapamil as compared to usual care. Clinically relevant associations were found between mortality or lack of clinical improvement and higher peak C-reactive protein (CRP) levels or nadir platelet count at 7, 10 and 15 days. Mortality rate increased by 73% every 5 mg/dL increment in peak CRP (HR 1.73, 95% CI 1.27-2.37) and was two-fold higher for every decrement of 100 units in nadir platelet count (HR 2.19, 95% CI 1.37-3.51). By cluster analysis, thresholds of 5 mg/dL for peak CRP and 187 × 103/mcL for nadir platelet count identified the phenogroup at greatest risk of dying. CONCLUSIONS: In this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis.

Long-term exercise training has been considered as an effective strategy to counteract age-related hormonal declines and minimise muscle atrophy. However, human data relating circulating hormone levels with motor nerve function are scant. The aims of the study were to explore associations between circulating sex hormone levels and motor unit (MU) characteristics in older men, including masters athletes competing in endurance and power events. Forty-three older men (mean ± SD age: 69.9 ± 4.6 years) were studied based on competitive status. The serum concentrations of dehydroepiandrosterone (DHEA), total testosterone (T) and estradiol were quantified using liquid chromatography mass spectrometry. Intramuscular electromyographic signals were recorded from vastus lateralis (VL) during 25% of maximum voluntary isometric contractions and processed to extract MU firing rate (FR), and motor unit potential (MUP) features. After adjusting for athletic status, MU FR was positively associated with DHEA levels (p = 0.019). Higher testosterone and estradiol were associated with lower MUP complexity; these relationships remained significant after adjusting for athletic status (p = 0.006 and p = 0.019, respectively). Circulating DHEA was positively associated with MU firing rate in these older men. Higher testosterone levels were associated with reduced MUP complexity, indicating reduced electrophysiological temporal dispersion, which is related to decreased differences in conduction times along axonal branches and/or MU fibres. Although evident in males only, this work highlights the potential of hormone administration as a therapeutic interventional strategy specifically targeting human motor units in older age.

Motor unit (MU) expansion enables rescue of denervated muscle fibres helping to ameliorate age-related muscle atrophy, with evidence to suggest master athletes are more successful at this remodelling. Electrophysiological data has suggested MUs located superficially are larger than those located deeper within young muscle. However, the effects of ageing and exercise on MU heterogeneity across deep and superficial aspects of vastus lateralis (VL) remain unclear. Intramuscular electromyography was used to record individual MU potentials (MUPs) and near fibre MUPs (NFMs) from deep and superficial regions of the VL during 25% maximum voluntary contractions, in 83 males (15 young (Y), 17 young athletes (YA), 22 old (O) and 29 master athletes (MA)). MUP size and complexity were assessed using area and number of turns, respectively. Multilevel mixed effects linear regression models were performed to investigate the effects of depth in each group. MUP area was greater in deep compared with superficial MUs in Y (p<0.001) and O (p=0.012) but not in YA (p=0.071) or MA (p=0.653). MUP amplitude and NF MUP area were greater, and MUPs were more complex in deep MUPs from Y, YA and O (all p<0.05) but did not differ across depth in MA (all p>0.07). These data suggest MU characteristics differ according to depth within the VL which may be influenced by both ageing and exercise. A more homogenous distribution of MUP size and complexity across muscle depths in older athletes may be a result of a greater degree of age-related MU adaptations.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle degeneration and weakness due to mutations in the dystrophin gene. The symptoms of DMD share similarities with those of accelerated aging. Recently, hydrogen sulfide (H2S) supplementation has been suggested to modulate the effects of age-related decline in muscle function, and metabolic H2S deficiencies have been implicated in affecting muscle mass in conditions such as phenylketonuria. We therefore evaluated the use of sodium GYY4137 (NaGYY), a H2S-releasing molecule, as a possible approach for DMD treatment. Using the dys-1(eg33) Caenorhabditis elegans DMD model, we found that NaGYY treatment (100 µM) improved movement, strength, gait, and muscle mitochondrial structure, similar to the gold-standard therapeutic treatment, prednisone (370 µM). The health improvements of either treatment required the action of the kinase JNK-1, the transcription factor SKN-1, and the NAD-dependent deacetylase SIR-2.1. The transcription factor DAF-16 was required for the health benefits of NaGYY treatment, but not prednisone treatment. AP39 (100 pM), a mitochondria-targeted H2S compound, also improved movement and strength in the dys-1(eg33) model, further implying that these improvements are mitochondria-based. Additionally, we found a decline in total sulfide and H2S-producing enzymes in dystrophin/utrophin knockout mice. Overall, our results suggest that H2S deficit may contribute to DMD pathology, and rectifying/overcoming the deficit with H2S delivery compounds has potential as a therapeutic approach to DMD treatment.

Objective: Disuse atrophy (DA) describes inactivity-induced skeletal muscle loss, through incompletely defined mechanisms. An intriguing observation is that individual muscles exhibit differing degrees of atrophy, despite exhibiting similar anatomical function/locations. We aimed to develop an innovative experimental paradigm to investigate Atrophy Resistant tibialis anterior (TA) and Atrophy Susceptible medial gastrocnemius (MG) muscles (aRaS) with a future view of uncovering central mechanisms. Method: Seven healthy young men (22 ± 1 year) underwent 15 days unilateral leg immobilisation (ULI). Participants had a single leg immobilised using a knee brace and air-boot to fix the leg (75° knee flexion) and ankle in place. Dual-energy X-ray absorptiometry (DXA), MRI and ultrasound scans of the lower leg were taken before and after the immobilisation period to determine changes in muscle mass. Techniques were developed for conchotome and microneedle TA/MG muscle biopsies following immobilisation (both limbs), and preliminary fibre typing analyses was conducted. Results: TA/MG muscles displayed comparable fibre type distribution of predominantly type I fibres (TA 67 ± 7%, MG 63 ± 5%). Following 15 days immobilisation, MG muscle volume (–2.8 ± 1.4%, p < 0.05) and muscle thickness decreased (−12.9 ± 1.6%, p < 0.01), with a positive correlation between changes in muscle volume and thickness (R2 = 0.31, p = 0.038). Importantly, both TA muscle volume and thickness remained unchanged. Conclusion: The use of this unique “aRaS” paradigm provides an effective and convenient means by which to study the mechanistic basis of divergent DA susceptibility in humans, which may facilitate new mechanistic insights, and by extension, mitigation of skeletal muscle atrophy during human DA.

Motor unit (MU) expansion enables rescue of denervated muscle fibres helping to ameliorate age-related muscle atrophy, with evidence to suggest master athletes are more successful at this remodelling. Electrophysiological data has suggested MUs located superficially are larger than those located deeper within young muscle. However, the effects of ageing and exercise on MU heterogeneity across deep and superficial aspects of vastus lateralis (VL) remain unclear. Intramuscular electromyography was used to record individual MU potentials (MUPs) and near fibre MUPs (NFMs) from deep and superficial regions of the VL during 25% maximum voluntary contractions, in 83 males (15 young (Y), 17 young athletes (YA), 22 old (O) and 29 master athletes (MA)). MUP size and complexity were assessed using area and number of turns, respectively. Multilevel mixed effects linear regression models were performed to investigate the effects of depth in each group. MUP area was greater in deep compared with superficial MUs in Y (p<0.001) and O (p=0.012) but not in YA (p=0.071) or MA (p=0.653). MUP amplitude and NF MUP area were greater, and MUPs were more complex in deep MUPs from Y, YA and O (all p<0.05) but did not differ across depth in MA (all p>0.07). These data suggest MU characteristics differ according to depth within the VL which may be influenced by both ageing and exercise. A more homogenous distribution of MUP size and complexity across muscle depths in older athletes may be a result of a greater degree of age-related MU adaptations.

Prolonged high-fat diets (HFD) can cause intramyocellular lipids (IMCL) accumulation that may negatively affect muscle function. We investigated the duration of a HFD required to instigate these changes, and whether effects are muscle-specific and aggravated in older age. Muscle morphology was determined in the soleus, extensor digitorum longus (EDL) and diaphragm muscles from female CD-1 mice divided into 5 groups: young fed a HFD for 8 weeks (YS-HFD, n=16), young fed a HFD for 16 weeks (YL-HFD, n=28) and young control (Y-CON, n=28). The young animals were 20 weeks old at the end of the experiment. Sixty 70-week-old female CD-1 mice received either a normal diet (O-CON, n=30) or a HFD for 9 weeks (OS-HFD, n=30). Body mass, body mass index and IMCL content increased in old OS-HFD (p≤0.003). In the young mice, this increase was seen in YL-HFD and not YS-HFD (p≤0.006). The soleus and diaphragm fibre cross-sectional area (FCSA) in YL-HFD was larger compared to Y-CON (p≤0.004) while old mice had a larger soleus FCSA compared to CON after only 9 weeks on a HFD (p<0.001). The FCSA of the EDL muscle did not differ significantly between groups. Oxidative capacity of fibres increased in young only, irrespective of HFD duration (p<0.001). High-fat diet-induced morphological changes occur earlier in the old animals when compared to young, and adaptations to HFD are muscle-specific with the EDL being least responsive.

Prolonged high-fat diets (HFD) can cause intramyocellular lipids (IMCL) accumulation that may negatively affect muscle function. We investigated the duration of a HFD required to instigate these changes, and whether effects are muscle-specific and aggravated in older age. Muscle morphology was determined in the soleus, extensor digitorum longus (EDL) and diaphragm muscles from female CD-1 mice divided into 5 groups: young fed a HFD for 8 weeks (YS-HFD, n=16), young fed a HFD for 16 weeks (YL-HFD, n=28) and young control (Y-CON, n=28). The young animals were 20 weeks old at the end of the experiment. Sixty 70-week-old female CD-1 mice received either a normal diet (O-CON, n=30) or a HFD for 9 weeks (OS-HFD, n=30). Body mass, body mass index and IMCL content increased in old OS-HFD (p≤0.003). In the young mice, this increase was seen in YL-HFD and not YS-HFD (p≤0.006). The soleus and diaphragm fibre cross-sectional area (FCSA) in YL-HFD was larger compared to Y-CON (p≤0.004) while old mice had a larger soleus FCSA compared to CON after only 9 weeks on a HFD (p<0.001). The FCSA of the EDL muscle did not differ significantly between groups. Oxidative capacity of fibres increased in young only, irrespective of HFD duration (p<0.001). High-fat diet-induced morphological changes occur earlier in the old animals when compared to young, and adaptations to HFD are muscle-specific with the EDL being least responsive.

© 2019 Elsevier Inc. One of the hallmarks of ageing is muscle wasting that may be preceded by morphological changes, such as capillary rarefaction. Muscle-specific changes in morphology in early ageing may differ between locomotor and respiratory muscles. To investigate this, we compared capillarization, fiber type composition, fiber cross-sectional area (FCSA) and oxidative capacity of individual fibers of the soleus (n = 6/5 for 20- and 79 weeks, respectively), extensor digitorum longus (EDL: n = 3/3) and diaphragm (n = 7/5) muscles in 20- (mature) and 79-week-old (early ageing) CD-1 female mice. There was no significant loss of soleus and EDL mass. The FCSA was larger and the capillary density lower at 79 than 20 weeks in the diaphragm, while in the EDL the opposite was found (both p ≤ 0.002) with no significant ageing-related differences in the soleus. The heterogeneity in capillary spacing, which may negatively impact on muscle oxygenation, was highest in muscles from 20-week-old mice, irrespective of muscle (p ≤ 0.011). Succinate dehydrogenase activity, indicative of oxidative capacity, and capillary to fiber ratio did not significantly change with age in any muscle. At all ages, the capillary supply to a fiber was positively related to FCSA in each muscle. We conclude that despite previously reported early age-related reductions in specific tension in both locomotor and respiratory muscles, morphological changes show a muscle-specific pattern in early ageing CD-1 mice. Specifically, early ageing was associated with 1) diaphragm hypertrophy 2) and fiber atrophy in the EDL that was not accompanied by angiogenesis, capillary rarefaction or reductions in oxidative capacity.

© 2019 Elsevier Inc. One of the hallmarks of ageing is muscle wasting that may be preceded by morphological changes, such as capillary rarefaction. Muscle-specific changes in morphology in early ageing may differ between locomotor and respiratory muscles. To investigate this, we compared capillarization, fiber type composition, fiber cross-sectional area (FCSA) and oxidative capacity of individual fibers of the soleus (n = 6/5 for 20- and 79 weeks, respectively), extensor digitorum longus (EDL: n = 3/3) and diaphragm (n = 7/5) muscles in 20- (mature) and 79-week-old (early ageing) CD-1 female mice. There was no significant loss of soleus and EDL mass. The FCSA was larger and the capillary density lower at 79 than 20 weeks in the diaphragm, while in the EDL the opposite was found (both p ≤ 0.002) with no significant ageing-related differences in the soleus. The heterogeneity in capillary spacing, which may negatively impact on muscle oxygenation, was highest in muscles from 20-week-old mice, irrespective of muscle (p ≤ 0.011). Succinate dehydrogenase activity, indicative of oxidative capacity, and capillary to fiber ratio did not significantly change with age in any muscle. At all ages, the capillary supply to a fiber was positively related to FCSA in each muscle. We conclude that despite previously reported early age-related reductions in specific tension in both locomotor and respiratory muscles, morphological changes show a muscle-specific pattern in early ageing CD-1 mice. Specifically, early ageing was associated with 1) diaphragm hypertrophy 2) and fiber atrophy in the EDL that was not accompanied by angiogenesis, capillary rarefaction or reductions in oxidative capacity.

© 2019 Piasecki, Ireland, Piasecki, Deere, Hannam, Tobias and McPhee. Masters endurance runners can epitomize healthy aging; being reflective of the physiological processes of aging without the compounded effects of inactivity. The primary aim of the present study was to determine, using cross-sectional data, whether individuals taking up training after the age of 50 years can achieve the same level of athletic performance and musculoskeletal characteristics in their older age as those who trained all of their adult lives. A total of 150 master endurance runners [age 68 (5) years; 111 male, 39 female] were divided into early starters (training all of their adulthood) and late starters (started training after age 50 years). A comparative non-athletic group of 59 healthy older adults [age 73 (4) years; 30 female, 29 male] were additionally included for analysis. Training intensity, age-graded performance (AGP) and musculoskeletal assessments were performed. Results showed that there was no difference between athlete groups for training intensity or age-graded performance, despite the 30-year difference in training history. Body fat percentage and leg lean mass did not differ between athlete groups, but were 17% lower and 12% greater, respectively, in athlete groups compared with controls. Power normalized to body mass did not differ between any groups. Spine BMD was lower in late starters than controls, while early starters did not differ from late starters or controls. Hip BMD did not differ between any of the groups. These findings show that the Masters athletes we studied that started intense endurance running after the age of 50 years had lower body fat and higher leg lean mass compared to non-athletes. Body composition and athletic performance of the late starters was very similar to those who trained all of their adult lives.

The evidence concerning the effects of exercise in older age on motor unit (MU) numbers, muscle fiber denervation and reinnervation cycles is inconclusive and it remains unknown whether any effects are dependent on the type of exercise undertaken or are localized to highly used muscles. MU characteristics of the vastus lateralis (VL) were assessed using surface and intramuscular electromyography in eighty-five participants, divided into sub groups based on age (young, old) and athletic discipline (control, endurance, power). In a separate study of the biceps brachii (BB), the same characteristics were compared in the favored and non-favored arms in eleven masters tennis players. Muscle size was assessed using MRI and ultrasound. In the VL, the CSA was greater in young compared to old, and power athletes had the largest CSA within their age groups. Motor unit potential (MUP) size was larger in all old compared to young (p < 0.001), with interaction contrasts showing this age-related difference was greater for endurance and power athletes than controls, and MUP size was greater in old athletes compared to old controls. In the BB, thickness did not differ between favored and non-favored arms (p = 0.575), but MUP size was larger in the favored arm (p < 0.001). Long-term athletic training does not prevent age-related loss of muscle size in the VL or BB, regardless of athletic discipline, but may facilitate more successful axonal sprouting and reinnervation of denervated fibers. These effects may be localized to muscles most involved in the exercise.

© 2019 Piasecki, Ireland, Piasecki, Deere, Hannam, Tobias and McPhee. Masters endurance runners can epitomize healthy aging; being reflective of the physiological processes of aging without the compounded effects of inactivity. The primary aim of the present study was to determine, using cross-sectional data, whether individuals taking up training after the age of 50 years can achieve the same level of athletic performance and musculoskeletal characteristics in their older age as those who trained all of their adult lives. A total of 150 master endurance runners [age 68 (5) years; 111 male, 39 female] were divided into early starters (training all of their adulthood) and late starters (started training after age 50 years). A comparative non-athletic group of 59 healthy older adults [age 73 (4) years; 30 female, 29 male] were additionally included for analysis. Training intensity, age-graded performance (AGP) and musculoskeletal assessments were performed. Results showed that there was no difference between athlete groups for training intensity or age-graded performance, despite the 30-year difference in training history. Body fat percentage and leg lean mass did not differ between athlete groups, but were 17% lower and 12% greater, respectively, in athlete groups compared with controls. Power normalized to body mass did not differ between any groups. Spine BMD was lower in late starters than controls, while early starters did not differ from late starters or controls. Hip BMD did not differ between any of the groups. These findings show that the Masters athletes we studied that started intense endurance running after the age of 50 years had lower body fat and higher leg lean mass compared to non-athletes. Body composition and athletic performance of the late starters was very similar to those who trained all of their adult lives.

One of the hallmarks of ageing is muscle wasting that may be preceded by morphological changes, such as capillary rarefaction. Muscle-specific changes in morphology in early ageing may differ between locomotor and respiratory muscles. To investigate this, we compared capillarization, fiber type composition, fiber cross-sectional area (FCSA) and oxidative capacity of individual fibers of the soleus (n = 6/5 for 20- and 79 weeks, respectively), extensor digitorum longus (EDL: n = 3/3) and diaphragm (n = 7/5) muscles in 20- (mature) and 79-week-old (early ageing) CD-1 female mice. There was no significant loss of soleus and EDL mass. The FCSA was larger and the capillary density lower at 79 than 20 weeks in the diaphragm, while in the EDL the opposite was found (both p ≤ 0.002) with no significant ageing-related differences in the soleus. The heterogeneity in capillary spacing, which may negatively impact on muscle oxygenation, was highest in muscles from 20-week-old mice, irrespective of muscle (p ≤ 0.011). Succinate dehydrogenase activity, indicative of oxidative capacity, and capillary to fiber ratio did not significantly change with age in any muscle. At all ages, the capillary supply to a fiber was positively related to FCSA in each muscle. We conclude that despite previously reported early age-related reductions in specific tension in both locomotor and respiratory muscles, morphological changes show a muscle-specific pattern in early ageing CD-1 mice. Specifically, early ageing was associated with 1) diaphragm hypertrophy 2) and fiber atrophy in the EDL that was not accompanied by angiogenesis, capillary rarefaction or reductions in oxidative capacity.

The evidence concerning the effects of exercise in older age on motor unit (MU) numbers, muscle fiber denervation and reinnervation cycles is inconclusive and it remains unknown whether any effects are dependent on the type of exercise undertaken or are localized to highly used muscles. MU characteristics of the vastus lateralis (VL) were assessed using surface and intramuscular electromyography in eighty-five participants, divided into sub groups based on age (young, old) and athletic discipline (control, endurance, power). In a separate study of the biceps brachii (BB), the same characteristics were compared in the favored and non-favored arms in eleven masters tennis players. Muscle size was assessed using MRI and ultrasound. In the VL, the CSA was greater in young compared to old, and power athletes had the largest CSA within their age groups. Motor unit potential (MUP) size was larger in all old compared to young (p < 0.001), with interaction contrasts showing this age-related difference was greater for endurance and power athletes than controls, and MUP size was greater in old athletes compared to old controls. In the BB, thickness did not differ between favored and non-favored arms (p = 0.575), but MUP size was larger in the favored arm (p < 0.001). Long-term athletic training does not prevent age-related loss of muscle size in the VL or BB, regardless of athletic discipline, but may facilitate more successful axonal sprouting and reinnervation of denervated fibers. These effects may be localized to muscles most involved in the exercise.

We examined bone density in older athletes and controls. Sprinters had greater hip and spine bone density than endurance athletes and controls, whereas values were similar in the latter two groups. These results could not be explained by differences in impact, muscle size or power between sprint and endurance athletes.We examined the relationship between prolonged participation in regular sprint or endurance running and skeletal health at key clinical sites in older age, and the factors responsible for any associations which we observed.We recruited 38 master sprint runners (28 males, 10 females, mean age 71 ± 7 years), 149 master endurance runners (111 males, 38 females, mean age 70 ± 6 years) and 59 non-athletic controls (29 males, 30 females, mean age 74 ± 5 years). Dual X-ray absorptiometry was used to assess hip and spine bone mineral density (BMD), body composition (lean and fat mass), whilst jump power was assessed with jumping mechanography. In athletes, vertical impacts were recorded over 7 days from a waist-worn accelerometer, and details of starting age, age-graded performance and training hours were recorded.In ANOVA models adjusted for sex, age, height, body composition, and jump power, sprinter hip BMD was 10 and 14% greater than that of endurance runners and controls respectively. Sprinter spine BMD was also greater than that of both endurance runners and controls. There were no differences in hip or spine BMD between endurance runners and controls. Stepwise regression showed only discipline (sprint/endurance), sex, and age as predictors of athlete spine BMD, whilst these variables and starting age were predictive of hip BMD.Regular running is associated with greater BMD at the fracture-prone hip and spine sites in master sprinters but not endurance runners. These benefits cannot be explained by indicators of mechanical loading measured in this study including vertical impacts, body composition or muscular output.

© 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society Key points: The age-related loss of muscle mass is related to the loss of innervating motor neurons and denervation of muscle fibres. Not all denervated muscle fibres are degraded; some may be reinnervated by an adjacent surviving neuron, which expands the innervating motor unit proportional to the numbers of fibres rescued. Enlarged motor units have larger motor unit potentials when measured using electrophysiological techniques. We recorded much larger motor unit potentials in relatively healthy older men compared to young men, but the older men with the smallest muscles (sarcopenia) had smaller motor unit potentials than healthy older men. These findings suggest that healthy older men reinnervate large numbers of muscle fibres to compensate for declining motor neuron numbers, but a failure to do so contributes to muscle loss in sarcopenic men. Abstract: Sarcopenia results from the progressive loss of skeletal muscle mass and reduced function in older age. It is likely to be associated with the well-documented reduction of motor unit numbers innervating limb muscles and the increase in size of surviving motor units via reinnervation of denervated fibres. However, no evidence exists to confirm the extent of motor unit remodelling in sarcopenic individuals. The aim of the present study was to compare motor unit size and number between young (n = 48), non-sarcopenic old (n = 13), pre-sarcopenic (n = 53) and sarcopenic (n = 29) men. Motor unit potentials (MUPs) were isolated from intramuscular and surface EMG recordings. The motor unit numbers were reduced in all groups of old compared with young men (all P < 0.001). MUPs were higher in non-sarcopenic and pre-sarcopenic men compared with young men (P = 0.039 and 0.001 respectively), but not in the vastus lateralis of sarcopenic old (P = 0.485). The results suggest that extensive motor unit remodell

The contributions of fiber atrophy, fiber loss, in situ specific force, and voluntary activation to weakness in sarcopenia remain unclear. To investigate, 40 older (20 women; age 72 ± 4 years) and 31 younger adults (15 women, age 22 ± 3 years) completed measurements. The knee extensor maximal voluntary torque (MVC) was measured as well as voluntary activation, patella tendon moment arm length, muscle volume, and fascicle architecture to estimate in situ specific force. Fiber cross-sectional area (FCSA), fiber numbers, and connective tissue contents were also estimated from vastus lateralis biopsies. The MVC, quadriceps volume, and specific force were 39%, 28%, and 17% lower, respectively, in old compared with young, but voluntary activation was not different. The difference in muscle size was due in almost equal proportions to lower type II FCSA and fewer fibers. Five years later (n = 23) the MVC, muscle volume and voluntary activation in old decreased an additional 12%, 6%, and 4%, respectively, but there was no further change in specific force. In situ specific force declines relatively early in older age and reduced voluntary activation occurs later, but the overall weakness in sarcopenia is mainly related to loss of both type I and II fibers and type II fiber atrophy.

© 2018 The Author(s) Purpose: Current methods for estimating muscle motor unit (MU) number provide values which are remarkably similar for muscles of widely differing size, probably because surface electrodes sample from similar and relatively small volumes in each muscle. We have evaluated an alternative means of estimating MU number that takes into account differences in muscle size. Methods: Intramuscular motor unit potentials (MUPs) were recorded and muscle cross-sectional area (CSA) was measured using MRI to provide a motor unit number estimate (iMUNE). This was compared to the traditional MUNE method, using compound muscle action potentials (CMAP) and surface motor unit potentials (sMUPs) recorded using surface electrodes. Data were collected from proximal and distal regions of the vastus lateralis (VL) in young and old men while test–retest reliability was evaluated with VL, tibialis anterior and biceps brachii. Results: MUPs, sMUPs and CMAPs were highly reliable (r = 0.84–0.91). The traditional MUNE, based on surface recordings, did not differ between proximal and distal sites of the VL despite the proximal CSA being twice the distal CSA. iMUNE, however, gave values that differed between young and old and were proportional to the muscle size. Conclusion: When evaluating the contribution that MU loss makes to muscle atrophy, such as in disease or ageing, it is important to have a method such as iMUNE, which takes into account any differences in total muscle size.

Background: Regular intense endurance exercise can lead to amenorrhea with possible adverse consequences for bone health. Objective: We compared whole-body and regional bone strength and skeletal muscle characteristics between amenorrheic (AA: n=14) and eumenorrheic (EA: n=15) elite adult female long distance runners and non-athletic controls (C: n=15). Study design and Participants: Participants completed three-day food diaries, dual energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT) and isometric maximal voluntary knee extension contraction (MVC). Results: Both athlete groups had a higher caloric intake than controls, with no significant difference between athlete groups. DXA revealed lower bone mineral density (BMD) at the trunk, rib, pelvis and lumbar spine in the AA than EA and C. pQCT showed greater bone size in the radius and tibia in EA and AA than C. The radius and tibia of AA had a larger endocortical circumference than C. Tibia bone mass and moments of inertia (Ix and Iy) were greater in AA and EA than C, whereas in the radius only the proximal Iy was larger in EA than C. Knee extensor MVC did not differ significantly between groups. Conclusions: Amenorrheic adult female elite long-distance runners had lower BMD in the trunk, lumbar spine, ribs and pelvis than eumenorrheic athletes and controls. The radius and tibia bone size and strength indicators were similar in amenorrheic and eumenorrheic athletes, suggesting that long bones of the limbs differ in their response to amenorrhea from bones in the trunk.

We examined bone density in older athletes and controls. Sprinters had greater hip and spine bone density than endurance athletes and controls, whereas values were similar in the latter two groups. These results could not be explained by differences in impact, muscle size or power between sprint and endurance athletes.We examined the relationship between prolonged participation in regular sprint or endurance running and skeletal health at key clinical sites in older age, and the factors responsible for any associations which we observed.We recruited 38 master sprint runners (28 males, 10 females, mean age 71 ± 7 years), 149 master endurance runners (111 males, 38 females, mean age 70 ± 6 years) and 59 non-athletic controls (29 males, 30 females, mean age 74 ± 5 years). Dual X-ray absorptiometry was used to assess hip and spine bone mineral density (BMD), body composition (lean and fat mass), whilst jump power was assessed with jumping mechanography. In athletes, vertical impacts were recorded over 7 days from a waist-worn accelerometer, and details of starting age, age-graded performance and training hours were recorded.In ANOVA models adjusted for sex, age, height, body composition, and jump power, sprinter hip BMD was 10 and 14% greater than that of endurance runners and controls respectively. Sprinter spine BMD was also greater than that of both endurance runners and controls. There were no differences in hip or spine BMD between endurance runners and controls. Stepwise regression showed only discipline (sprint/endurance), sex, and age as predictors of athlete spine BMD, whilst these variables and starting age were predictive of hip BMD.Regular running is associated with greater BMD at the fracture-prone hip and spine sites in master sprinters but not endurance runners. These benefits cannot be explained by indicators of mechanical loading measured in this study including vertical impacts, body composition or muscular output.

© 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society Key points: The age-related loss of muscle mass is related to the loss of innervating motor neurons and denervation of muscle fibres. Not all denervated muscle fibres are degraded; some may be reinnervated by an adjacent surviving neuron, which expands the innervating motor unit proportional to the numbers of fibres rescued. Enlarged motor units have larger motor unit potentials when measured using electrophysiological techniques. We recorded much larger motor unit potentials in relatively healthy older men compared to young men, but the older men with the smallest muscles (sarcopenia) had smaller motor unit potentials than healthy older men. These findings suggest that healthy older men reinnervate large numbers of muscle fibres to compensate for declining motor neuron numbers, but a failure to do so contributes to muscle loss in sarcopenic men. Abstract: Sarcopenia results from the progressive loss of skeletal muscle mass and reduced function in older age. It is likely to be associated with the well-documented reduction of motor unit numbers innervating limb muscles and the increase in size of surviving motor units via reinnervation of denervated fibres. However, no evidence exists to confirm the extent of motor unit remodelling in sarcopenic individuals. The aim of the present study was to compare motor unit size and number between young (n = 48), non-sarcopenic old (n = 13), pre-sarcopenic (n = 53) and sarcopenic (n = 29) men. Motor unit potentials (MUPs) were isolated from intramuscular and surface EMG recordings. The motor unit numbers were reduced in all groups of old compared with young men (all P < 0.001). MUPs were higher in non-sarcopenic and pre-sarcopenic men compared with young men (P = 0.039 and 0.001 respectively), but not in the vastus lateralis of sarcopenic old (P = 0.485). The results suggest that extensive motor unit remodell

The contributions of fiber atrophy, fiber loss, in situ specific force, and voluntary activation to weakness in sarcopenia remain unclear. To investigate, 40 older (20 women; age 72 ± 4 years) and 31 younger adults (15 women, age 22 ± 3 years) completed measurements. The knee extensor maximal voluntary torque (MVC) was measured as well as voluntary activation, patella tendon moment arm length, muscle volume, and fascicle architecture to estimate in situ specific force. Fiber cross-sectional area (FCSA), fiber numbers, and connective tissue contents were also estimated from vastus lateralis biopsies. The MVC, quadriceps volume, and specific force were 39%, 28%, and 17% lower, respectively, in old compared with young, but voluntary activation was not different. The difference in muscle size was due in almost equal proportions to lower type II FCSA and fewer fibers. Five years later (n = 23) the MVC, muscle volume and voluntary activation in old decreased an additional 12%, 6%, and 4%, respectively, but there was no further change in specific force. In situ specific force declines relatively early in older age and reduced voluntary activation occurs later, but the overall weakness in sarcopenia is mainly related to loss of both type I and II fibers and type II fiber atrophy.

© 2018 The Author(s) Purpose: Current methods for estimating muscle motor unit (MU) number provide values which are remarkably similar for muscles of widely differing size, probably because surface electrodes sample from similar and relatively small volumes in each muscle. We have evaluated an alternative means of estimating MU number that takes into account differences in muscle size. Methods: Intramuscular motor unit potentials (MUPs) were recorded and muscle cross-sectional area (CSA) was measured using MRI to provide a motor unit number estimate (iMUNE). This was compared to the traditional MUNE method, using compound muscle action potentials (CMAP) and surface motor unit potentials (sMUPs) recorded using surface electrodes. Data were collected from proximal and distal regions of the vastus lateralis (VL) in young and old men while test–retest reliability was evaluated with VL, tibialis anterior and biceps brachii. Results: MUPs, sMUPs and CMAPs were highly reliable (r = 0.84–0.91). The traditional MUNE, based on surface recordings, did not differ between proximal and distal sites of the VL despite the proximal CSA being twice the distal CSA. iMUNE, however, gave values that differed between young and old and were proportional to the muscle size. Conclusion: When evaluating the contribution that MU loss makes to muscle atrophy, such as in disease or ageing, it is important to have a method such as iMUNE, which takes into account any differences in total muscle size.

Background: Regular intense endurance exercise can lead to amenorrhea with possible adverse consequences for bone health. Objective: We compared whole-body and regional bone strength and skeletal muscle characteristics between amenorrheic (AA: n=14) and eumenorrheic (EA: n=15) elite adult female long distance runners and non-athletic controls (C: n=15). Study design and Participants: Participants completed three-day food diaries, dual energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT) and isometric maximal voluntary knee extension contraction (MVC). Results: Both athlete groups had a higher caloric intake than controls, with no significant difference between athlete groups. DXA revealed lower bone mineral density (BMD) at the trunk, rib, pelvis and lumbar spine in the AA than EA and C. pQCT showed greater bone size in the radius and tibia in EA and AA than C. The radius and tibia of AA had a larger endocortical circumference than C. Tibia bone mass and moments of inertia (Ix and Iy) were greater in AA and EA than C, whereas in the radius only the proximal Iy was larger in EA than C. Knee extensor MVC did not differ significantly between groups. Conclusions: Amenorrheic adult female elite long-distance runners had lower BMD in the trunk, lumbar spine, ribs and pelvis than eumenorrheic athletes and controls. The radius and tibia bone size and strength indicators were similar in amenorrheic and eumenorrheic athletes, suggesting that long bones of the limbs differ in their response to amenorrhea from bones in the trunk.

We report on the development, installation and operation of the first three of seven stations deployed at the ARIANNA site's pilot Hexagonal Radio Array in Antarctica. The primary goal of the ARIANNA project is to observe ultra-high energy (>100 PeV) cosmogenic neutrino signatures using a large array of autonomous stations each dispersed 1 km apart on the surface of the Ross Ice Shelf. Sensing radio emissions of 100 MHz to 1 GHz, each station in the array contains RF antennas, amplifiers, 1.92 G-sample/s, 850 MHz bandwidth signal acquisition circuitry, pattern-matching trigger capabilities, an embedded CPU, 32 GB of solid-state data storage, and long-distance wireless and satellite communications. Power is provided by the sun and LiFePO4 storage batteries, and the stations consume an average of 7W of power. Operation on solar power has resulted in >=58% per calendar-year live-time. The station's pattern-trigger capabilities reduce the trigger rates to a few milli-Hertz with 4-sigma thresholds while retaining good stability and high efficiency for neutrino signals. The timing resolution of the station has been found to be 0.049 ps, RMS, and the angular precision of event reconstructions of signals bounced off of the sea-ice interface of the Ross Ice Shelf ranged from 0.14 to 0.17 degrees. A new fully-synchronous 2+ G-sample/s, 1.5 GHz bandwidth 4-channel signal acquisition chip with deeper memory and flexible >600 MHz, <1 mV RMS sensitivity triggering has been designed and incorporated into a single-board data acquisition and control system that uses an average of only 1.7W of power. Along with updated amplifiers, these new systems are expected to be deployed during the 2014-2015 Austral summer to complete the Hexagonal Radio Array.

Muscle health is a critical component in the struggle against physical frailty and the efforts to maintain metabolic health until the limit of chronological age. Consensus opinion is to evaluate muscle health in terms of muscle mass, strength and functional capability. There has been considerable variability in the components of muscle health which have been investigated in addition to variability in the tools of assessment and protocol for measurement. This is in stark contrast to the validated measurement of bone health across the adult life span. The purpose of this review was to identify indices of muscle mass, strength and functional capability most responsive to change with ageing and where possible to provide an estimate of the rate of change. We suggest lean tissue mass (LTM) or skeletal muscle (SM) is best evaluated from the thigh region due to its greater responsiveness to ageing compared to the whole body. The anterior compartment of the thigh region undergoes a preferential age-related decline in SM and force generating capacity. Therefore, we suggest that knee extensor torque is measured to represent the force generating capacity of the thigh and subsequently, to express muscle quality (strength per unit tissue). Finally, we suggest measures of functional capability which allow participants perform to a greater maximum are most appropriate to track age-related difference in functional capacity across the adult lifespan. This is due to their ability encompass a broad spectrum of abilities. This review suggests indices of muscular health for which reference ranges can be generated across the lifespan.

Muscle health is a critical component in the struggle against physical frailty and the efforts to maintain metabolic health until the limit of chronological age. Consensus opinion is to evaluate muscle health in terms of muscle mass, strength and functional capability. There has been considerable variability in the components of muscle health which have been investigated in addition to variability in the tools of assessment and protocol for measurement. This is in stark contrast to the validated measurement of bone health across the adult life span. The purpose of this review was to identify indices of muscle mass, strength and functional capability most responsive to change with aging and where possible to provide an estimate of the rate of change. We suggest lean tissue mass (LTM) or skeletal muscle (SM) is best evaluated from the thigh region due to its greater responsiveness to ageing compared to the whole body. The anterior compartment of the thigh region undergoes a preferential age-related decline in SM and force generating capacity. Therefore we suggest that knee extensor torque is measured to represent the force generating capacity of the thigh and subsequently to express muscle quality (strength per unit tissue). Finally, we suggest measures of functional capability which allow participants perform to a greater maximum are most appropriate to track age-related difference in functional capacity across the adult lifespan due to their ability encompass a broad spectrum of abilities. This review suggests indices of muscular health for which reference ranges can be generated across the lifespan.

Muscle health is a critical component in the struggle against physical frailty and the efforts to maintain metabolic health until the limit of chronological age. Consensus opinion is to evaluate muscle health in terms of muscle mass, strength and functional capability. There has been considerable variability in the components of muscle health which have been investigated in addition to variability in the tools of assessment and protocol for measurement. This is in stark contrast to the validated measurement of bone health across the adult life span. The purpose of this review was to identify indices of muscle mass, strength and functional capability most responsive to change with aging and where possible to provide an estimate of the rate of change. We suggest lean tissue mass (LTM) or skeletal muscle (SM) is best evaluated from the thigh region due to its greater responsiveness to ageing compared to the whole body. The anterior compartment of the thigh region undergoes a preferential age-related decline in SM and force generating capacity. Therefore we suggest that knee extensor torque is measured to represent the force generating capacity of the thigh and subsequently to express muscle quality (strength per unit tissue). Finally, we suggest measures of functional capability which allow participants perform to a greater maximum are most appropriate to track age-related difference in functional capacity across the adult lifespan due to their ability encompass a broad spectrum of abilities. This review suggests indices of muscular health for which reference ranges can be generated across the lifespan.

Muscle health is a critical component in the struggle against physical frailty and the efforts to maintain metabolic health until the limit of chronological age. Consensus opinion is to evaluate muscle health in terms of muscle mass, strength and functional capability. There has been considerable variability in the components of muscle health which have been investigated in addition to variability in the tools of assessment and protocol for measurement. This is in stark contrast to the validated measurement of bone health across the adult life span. The purpose of this review was to identify indices of muscle mass, strength and functional capability most responsive to change with ageing and where possible to provide an estimate of the rate of change. We suggest lean tissue mass (LTM) or skeletal muscle (SM) is best evaluated from the thigh region due to its greater responsiveness to ageing compared to the whole body. The anterior compartment of the thigh region undergoes a preferential age-related decline in SM and force generating capacity. Therefore, we suggest that knee extensor torque is measured to represent the force generating capacity of the thigh and subsequently, to express muscle quality (strength per unit tissue). Finally, we suggest measures of functional capability which allow participants perform to a greater maximum are most appropriate to track age-related difference in functional capacity across the adult lifespan. This is due to their ability encompass a broad spectrum of abilities. This review suggests indices of muscular health for which reference ranges can be generated across the lifespan.

The aim of this study was to compare postural sway during a series of static balancing tasks and during five chair rises between healthy young (mean (SEM) age 26(1) yrs), healthy old (age 67(1) yrs) and master athlete runners (age 67(1) yrs; competing and training for the previous 51(5) yrs) using the Microsoft Kinect One. The healthy old had more sway than young in all balance tasks. The master athletes had similar sway to young during two-leg balancing and one leg standing with eyes open. When balancing on one-leg with eyes closed, both the healthy old and the master athletes had around 17-fold more sway than young. The healthy old and master athletes also had less anterio-posterior movement during chair rising compared with young. These results suggest that masters runners are not spared from the age-associated decline in postural stability and may benefit from specific balance training.

Muscle motor unit numbers decrease markedly in old age, while remaining motor units are enlarged and can have reduced neuromuscular junction transmission stability. However, it is possible that regular intense physical activity throughout life can attenuate this remodeling. The aim of this study was to compare the number, size, and neuromuscular junction transmission stability of tibialis anterior (TA) motor units in healthy young and older men with those of exceptionally active master runners. The distribution of motor unit potential (MUP) size was determined from intramuscular electromyographic signals recorded in healthy male Young (mean ± SD, 26 ± 5 years), Old (71 ± 4 years) and Master Athletes (69 ± 3 years). Relative differences between groups in numbers of motor units was assessed using two methods, one comparing MUP size and muscle cross-sectional area (CSA) determined with MRI, the other comparing surface recorded MUPs with maximal compound muscle action potentials and commonly known as a "motor unit number estimate (MUNE)". Near fiber (NF) jiggle was measured to assess neuromuscular junction transmission stability. TA CSA did not differ between groups. MUNE values for the Old and Master Athletes were 45% and 40%, respectively, of the Young. Intramuscular MUPs of Old and Master Athletes were 43% and 56% larger than Young. NF jiggle was slightly higher in the Master Athletes, with no difference between Young and Old. These results show substantial and similar motor unit loss and remodeling in Master Athletes and Old individuals compared with Young, which suggests that lifelong training does not attenuate the age-related loss of motor units.

Background The purpose of this study was to examine whether very short duration, very high intensity sprint interval training (SIT) leads to loss of body fat mass in association with improvements to VO2max and fatty acid oxidation, and to assess the extent of sex dimorphism in these physiological responses. Methods A total of 24 men and 17 women (mean (SEM) age: 39 (±2) years; body mass index 24.6 (0.6)) completed measurements of the maximal rate of oxygen uptake (VO2max) and fatty acid oxidation (FATmax). Body fat and lean mass were measured by dual emission x-ray absorptiometry, and fasting blood lipid, glucose and insulin profiles were assessed before and after training. SIT consisted of 4×20 s sprints on a cycle ergometer at approximately 175% VO2max, three times per week for 12 weeks. Results Fat mass decreased by 1.0 kg, although men lost statistically significantly more fat than women both when expressed in Kg and as % body fat. VO2max increased by around 9%, but women improved VO2max significantly more than men. FATmax improved by around 13%, but fasting plasma glucose, insulin, total triglyceride, total cholesterol and high-density lipoprotein (HDL) did not change after training, while low-density lipoprotein decreased by 8% (p=0.028) and the HDL:Total Cholesterol ratio improved by 6%. There were no sex differences in these metabolic responses to training. Conclusions These results show lower body fat %, and higher rates of fatty acid oxidation and VO2max after 12 weeks of training for just 4 min per week. Notably, women improved VO2max more than men, while men lost more fat than women.

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

The aim of this study was to compare postural sway during a series of static balancing tasks and during five chair rises between healthy young (mean (SEM) age 26(1) yrs), healthy old (age 67(1) yrs) and master athlete runners (age 67(1) yrs; competing and training for the previous 51(5) yrs) using the Microsoft Kinect One. The healthy old had more sway than young in all balance tasks. The master athletes had similar sway to young during two-leg balancing and one leg standing with eyes open. When balancing on one-leg with eyes closed, both the healthy old and the master athletes had around 17-fold more sway than young. The healthy old and master athletes also had less anterio-posterior movement during chair rising compared with young. These results suggest that masters runners are not spared from the age-associated decline in postural stability and may benefit from specific balance training.

Background The purpose of this study was to examine whether very short duration, very high intensity sprint interval training (SIT) leads to loss of body fat mass in association with improvements to VO2max and fatty acid oxidation, and to assess the extent of sex dimorphism in these physiological responses. Methods A total of 24 men and 17 women (mean (SEM) age: 39 (±2) years; body mass index 24.6 (0.6)) completed measurements of the maximal rate of oxygen uptake (VO2max) and fatty acid oxidation (FATmax). Body fat and lean mass were measured by dual emission x-ray absorptiometry, and fasting blood lipid, glucose and insulin profiles were assessed before and after training. SIT consisted of 4×20 s sprints on a cycle ergometer at approximately 175% VO2max, three times per week for 12 weeks. Results Fat mass decreased by 1.0 kg, although men lost statistically significantly more fat than women both when expressed in Kg and as % body fat. VO2max increased by around 9%, but women improved VO2max significantly more than men. FATmax improved by around 13%, but fasting plasma glucose, insulin, total triglyceride, total cholesterol and high-density lipoprotein (HDL) did not change after training, while low-density lipoprotein decreased by 8% (p=0.028) and the HDL:Total Cholesterol ratio improved by 6%. There were no sex differences in these metabolic responses to training. Conclusions These results show lower body fat %, and higher rates of fatty acid oxidation and VO2max after 12 weeks of training for just 4 min per week. Notably, women improved VO2max more than men, while men lost more fat than women.

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

BACKGROUND & AIM: Sarcopenia, the age-related decrease in muscle mass, strength, and function, is a main cause of reduced mobility, increased falls, fractures and nursing home admissions. Cross-sectional and prospective studies indicate that sarcopenia may be influenced in part by reversible factors like nutritional intake. The aim of this study was to compare functional and nutritional status, body composition, and quality of life of older adults between age and sex-matched older adults with and without sarcopenia. METHODS: In a multi-centre setting, non-sarcopenic older adults (n = 66, mean ± SD: 71 ± 4 y), i.e. Short Physical Performance Battery (SPPB): 11-12 and normal skeletal muscle mass index, were recruited to match 1:1 by age and sex to previously recruited adults with sarcopenia: SPPB 4-9 and low skeletal muscle mass index. Health-related quality of life, self-reported physical activity levels and dietary intakes were measured using the EQ-5D scale and index, Physical Activity Scale for the Elderly (PASE), and 3-day prospective diet records, respectively. Concentrations of 25-OH-vitamin D, α-tocopherol (adjusted for cholesterol), folate, and vitamin B-12 were assessed in serum samples. RESULTS: In addition to the defined components of sarcopenia, i.e. muscle mass, strength and function, reported physical activity levels and health-related quality of life were lower in the sarcopenic adults (p < 0.001). For similar energy intakes (mean ± SD: sarcopenic, 1710 ± 418; non-sarcopenic, 1745 ± 513, p = 0.50), the sarcopenic group consumed less protein/kg (-6%), vitamin D (-38%), vitamin B-12 (-22%), magnesium (-6%), phosphorus (-5%), and selenium (-2%) (all p < 0.05) compared to the non-sarcopenic controls. The serum concentration of vitamin B-12 was 15% lower in the sarcopenic group (p = 0.015), and all other nutrient concentrations were similar between groups. CONCLUSIONS: In non-malnourished older adults with and without sarcopenia, we observed that sarcopenia

The Antarctic Ross Ice Shelf Antenna Neutrino Array (ARIANNA) is a high-energy neutrino detector designed to record the Askaryan electric field signature of cosmogenic neutrino interactions in ice. To understand the inherent radio-frequency (RF) neutrino signature, the time-domain response of the ARIANNA RF receiver must be measured. ARIANNA uses Create CLP5130-2N log-periodic dipole arrays (LPDAs). The associated effective height operator converts incident electric fields to voltage waveforms at the LDPA terminals. The effective height versus time and incident angle was measured, along with the associated response of the ARIANNA RF amplifier. The results are verified by correlating to field measurements in air and ice, using oscilloscopes. Finally, theoretical models for the Askaryan electric field are combined with the detector response to predict the neutrino signature.

Voluntary control of skeletal muscle enables humans to interact with and manipulate the environment. Lower muscle mass, weakness and poor coordination are common complaints in older age and reduce physical capabilities. Attention has focused on ways of maintaining muscle size and strength by exercise, diet or hormone replacement. Without appropriate neural innervation, however, muscle cannot function. Emerging evidence points to a neural basis of muscle loss. Motor unit number estimates indicate that by age around 71 years, healthy older people have around 40 % fewer motor units. The surviving low- and moderate-threshold motor units recruited for moderate intensity contractions are enlarged by around 50 % and show increased fibre density, presumably due to collateral reinnervation of denervated fibres. Motor unit potentials show increased complexity and the stability of neuromuscular junction transmissions is decreased. The available evidence is limited by a lack of longitudinal studies, relatively small sample sizes, a tendency to examine the small peripheral muscles and relatively few investigations into the consequences of motor unit remodelling for muscle size and control of movements in older age. Loss of motor neurons and remodelling of surviving motor units constitutes the major change in ageing muscles and probably contributes to muscle loss and functional impairments. The deterioration and remodelling of motor units likely imposes constraints on the way in which the central nervous system controls movements.

INTRODUCTION: The anterior thigh muscles are particularly susceptible to muscle loss and weakness during ageing, but it remains unclear how this is associated with changes to neuromuscular structure and function in terms of motor unit (MU) number, size and MU potential (MUP) stability. METHODS: Intramuscular and surface electromyographic (EMG) signals were recorded from the vastus lateralis (VL) during voluntary contractions held at 25% maximal knee extensor strength in 22 young (25.3 ± 4.8yrs) and 20 physically active older men (71.4 ± 6.2yrs). MUP size, firing rates, phases, turns and near fibre (NF) jiggle were determined and motor unit number estimates (MUNEs) were made by comparing average surface MUP with maximal electrically-evoked compound muscle action potentials. Quadriceps cross-sectional area was measured by magnetic resonance imaging. RESULTS: 379 individual MUs were sampled in young and 346 in older men. Compared with young, the older MUs had 8% lower firing rates and larger MUP size (∼+25%) as well as increased complexity evidenced as, phases (+13%), turns (+20%) and NF jiggle (+11%) (all P < 0.0005). The MUNE values (derived from the area of muscle in range of the surface-electrode) in older subjects were around 70% of the young (P < 0.05). Taking into consideration the 30% smaller cross-sectional area of the VL, the total number of MUs in the older muscles was between 50-60% lower than in the young (P < 0.0005). CONCLUSION: A large portion of the VL MU pool is lost in older men and those recruited during moderate intensity contractions were enlarged and less stable. These MU changes were evident before clinically relevant changes to muscle function were apparent; nevertheless, the changes in MU number and size are likely to be a prelude to future movement problems. This article is protected by copyright. All rights reserved.

The Antarctic Ross Ice Shelf Antenna Neutrino Array (ARIANNA) is a high-energy neutrino detector designed to record the Askaryan electric field signature of cosmogenic neutrino interactions in ice. To understand the inherent radio-frequency (RF) neutrino signature, the time-domain response of the ARIANNA RF receiver must be measured. ARIANNA uses Create CLP5130-2N log-periodic dipole arrays (LPDAs). The associated effective height operator converts incident electric fields to voltage waveforms at the LDPA terminals. The effective height versus time and incident angle was measured, along with the associated response of the ARIANNA RF amplifier. The results are verified by correlating to field measurements in air and ice, using oscilloscopes. Finally, theoretical models for the Askaryan electric field are combined with the detector response to predict the neutrino signature.

INTRODUCTION: The anterior thigh muscles are particularly susceptible to muscle loss and weakness during ageing, but it remains unclear how this is associated with changes to neuromuscular structure and function in terms of motor unit (MU) number, size and MU potential (MUP) stability. METHODS: Intramuscular and surface electromyographic (EMG) signals were recorded from the vastus lateralis (VL) during voluntary contractions held at 25% maximal knee extensor strength in 22 young (25.3 ± 4.8yrs) and 20 physically active older men (71.4 ± 6.2yrs). MUP size, firing rates, phases, turns and near fibre (NF) jiggle were determined and motor unit number estimates (MUNEs) were made by comparing average surface MUP with maximal electrically-evoked compound muscle action potentials. Quadriceps cross-sectional area was measured by magnetic resonance imaging. RESULTS: 379 individual MUs were sampled in young and 346 in older men. Compared with young, the older MUs had 8% lower firing rates and larger MUP size (∼+25%) as well as increased complexity evidenced as, phases (+13%), turns (+20%) and NF jiggle (+11%) (all P < 0.0005). The MUNE values (derived from the area of muscle in range of the surface-electrode) in older subjects were around 70% of the young (P < 0.05). Taking into consideration the 30% smaller cross-sectional area of the VL, the total number of MUs in the older muscles was between 50-60% lower than in the young (P < 0.0005). CONCLUSION: A large portion of the VL MU pool is lost in older men and those recruited during moderate intensity contractions were enlarged and less stable. These MU changes were evident before clinically relevant changes to muscle function were apparent; nevertheless, the changes in MU number and size are likely to be a prelude to future movement problems. This article is protected by copyright. All rights reserved.

Voluntary control of skeletal muscle enables humans to interact with and manipulate the environment. Lower muscle mass, weakness and poor coordination are common complaints in older age and reduce physical capabilities. Attention has focused on ways of maintaining muscle size and strength by exercise, diet or hormone replacement. Without appropriate neural innervation, however, muscle cannot function. Emerging evidence points to a neural basis of muscle loss. Motor unit number estimates indicate that by age around 71 years, healthy older people have around 40 % fewer motor units. The surviving low- and moderate-threshold motor units recruited for moderate intensity contractions are enlarged by around 50 % and show increased fibre density, presumably due to collateral reinnervation of denervated fibres. Motor unit potentials show increased complexity and the stability of neuromuscular junction transmissions is decreased. The available evidence is limited by a lack of longitudinal studies, relatively small sample sizes, a tendency to examine the small peripheral muscles and relatively few investigations into the consequences of motor unit remodelling for muscle size and control of movements in older age. Loss of motor neurons and remodelling of surviving motor units constitutes the major change in ageing muscles and probably contributes to muscle loss and functional impairments. The deterioration and remodelling of motor units likely imposes constraints on the way in which the central nervous system controls movements.

We report on the development, installation and operation of the first three of seven stations deployed at the ARIANNA site's pilot Hexagonal Radio Array in Antarctica. The primary goal of the ARIANNA project is to observe ultra-high energy (>100 PeV) cosmogenic neutrino signatures using a large array of autonomous stations each dispersed 1 km apart on the surface of the Ross Ice Shelf. Sensing radio emissions of 100 MHz to 1 GHz, each station in the array contains RF antennas, amplifiers, 1.92 G-sample/s, 850 MHz bandwidth signal acquisition circuitry, pattern-matching trigger capabilities, an embedded CPU, 32 GB of solid-state data storage, and long-distance wireless and satellite communications. Power is provided by the sun and LiFePO4 storage batteries, and the stations consume an average of 7W of power. Operation on solar power has resulted in >=58% per calendar-year live-time. The station's pattern-trigger capabilities reduce the trigger rates to a few milli-Hertz with 4-sigma thresholds while retaining good stability and high efficiency for neutrino signals. The timing resolution of the station has been found to be 0.049 ps, RMS, and the angular precision of event reconstructions of signals bounced off of the sea-ice interface of the Ross Ice Shelf ranged from 0.14 to 0.17 degrees. A new fully-synchronous 2+ G-sample/s, 1.5 GHz bandwidth 4-channel signal acquisition chip with deeper memory and flexible >600 MHz, <1 mV RMS sensitivity triggering has been designed and incorporated into a single-board data acquisition and control system that uses an average of only 1.7W of power. Along with updated amplifiers, these new systems are expected to be deployed during the 2014-2015 Austral summer to complete the Hexagonal Radio Array.

We report on the development, installation and operation of the first three of seven stations deployed at the ARIANNA site's pilot Hexagonal Radio Array in Antarctica. The primary goal of the ARIANNA project is to observe ultra-high energy (>100 PeV) cosmogenic neutrino signatures using a large array of autonomous stations each dispersed 1 km apart on the surface of the Ross Ice Shelf. Sensing radio emissions of 100 MHz to 1 GHz, each station in the array contains RF antennas, amplifiers, 1.92 G-sample/s, 850 MHz bandwidth signal acquisition circuitry, pattern-matching trigger capabilities, an embedded CPU, 32 GB of solid-state data storage, and long-distance wireless and satellite communications. Power is provided by the sun and LiFePO4 storage batteries, and the stations consume an average of 7W of power. Operation on solar power has resulted in >=58% per calendar-year live-time. The station's pattern-trigger capabilities reduce the trigger rates to a few milli-Hertz with 4-sigma thresholds while retaining good stability and high efficiency for neutrino signals. The timing resolution of the station has been found to be 0.049 ps, RMS, and the angular precision of event reconstructions of signals bounced off of the sea-ice interface of the Ross Ice Shelf ranged from 0.14 to 0.17 degrees. A new fully-synchronous 2+ G-sample/s, 1.5 GHz bandwidth 4-channel signal acquisition chip with deeper memory and flexible >600 MHz, <1 mV RMS sensitivity triggering has been designed and incorporated into a single-board data acquisition and control system that uses an average of only 1.7W of power. Along with updated amplifiers, these new systems are expected to be deployed during the 2014-2015 Austral summer to complete the Hexagonal Radio Array., Comment: 17 Page, 27 Figures, 1 Table

The Antarctic Ross Ice Shelf Antenna Neutrino Array (ARIANNA) is a high-energy neutrino detector designed to record the Askaryan electric field signature of cosmogenic neutrino interactions in ice. To understand the inherent radio-frequency (RF) neutrino signature, the time-domain response of the ARIANNA RF receiver must be measured. ARIANNA uses Create CLP5130-2N log-periodic dipole arrays (LPDAs). The associated effective height operator converts incident electric fields to voltage waveforms at the LDPA terminals. The effective height versus time and incident angle was measured, along with the associated response of the ARIANNA RF amplifier. The results are verified by correlating to field measurements in air and ice, using oscilloscopes. Finally, theoretical models for the Askaryan electric field are combined with the detector response to predict the neutrino signature., Comment: 13 pages, 19 figures, in press at Astroparticle Physics Journal. Contact: J.C. Hanson (j529h838@ku.edu)

We report on the development, installation and operation of the first three of seven stations deployed at the ARIANNA site's pilot Hexagonal Radio Array in Antarctica. The primary goal of the ARIANNA project is to observe ultra-high energy (>100 PeV) cosmogenic neutrino signatures using a large array of autonomous stations each dispersed 1 km apart on the surface of the Ross Ice Shelf. Sensing radio emissions of 100 MHz to 1 GHz, each station in the array contains RF antennas, amplifiers, 1.92 G-sample/s, 850 MHz bandwidth signal acquisition circuitry, pattern-matching trigger capabilities, an embedded CPU, 32 GB of solid-state data storage, and long-distance wireless and satellite communications. Power is provided by the sun and LiFePO4 storage batteries, and the stations consume an average of 7W of power. Operation on solar power has resulted in >=58% per calendar-year live-time. The station's pattern-trigger capabilities reduce the trigger rates to a few milli-Hertz with 4-sigma thresholds while retaining good stability and high efficiency for neutrino signals. The timing resolution of the station has been found to be 0.049 ps, RMS, and the angular precision of event reconstructions of signals bounced off of the sea-ice interface of the Ross Ice Shelf ranged from 0.14 to 0.17 degrees. A new fully-synchronous 2+ G-sample/s, 1.5 GHz bandwidth 4-channel signal acquisition chip with deeper memory and flexible >600 MHz, <1 mV RMS sensitivity triggering has been designed and incorporated into a single-board data acquisition and control system that uses an average of only 1.7W of power. Along with updated amplifiers, these new systems are expected to be deployed during the 2014-2015 Austral summer to complete the Hexagonal Radio Array.