Activation of skeletal muscle mechanoreceptors and nociceptors reduces the exercise performance of the contralateral homologous muscles.

Increasing evidence suggests that activation of muscle nerve afferents may inhibit central motor drive, affecting contractile performance of remote exercising muscles. Although these effects are well documented for metaboreceptors, very little is known about the activation of mechano- and mechanonociceptive afferents on performance fatigability. Therefore, the purpose of the present study was to examine the influence of mechanoreceptors and nociceptors on performance fatigability. Eight healthy young males undertook four randomized experimental sessions on separate occasions in which the experimental knee extensors were the following: 1) resting (CTRL), 2) passively stretched (ST), 3) resting with delayed onset muscle soreness (DOMS), or 4) passively stretched with DOMS (DOMS+ST), whereas the contralateral leg performed an isometric time to task failure (TTF). Changes in maximal voluntary contraction (ΔMVC), potentiated twitch force (ΔQtw,pot), and voluntary muscle activation (ΔVA) were also assessed. TTF was reduced in DOMS+ST (-43%) and ST (-29%) compared with CTRL. DOMS+ST also showed a greater reduction of VA (-25% vs. -8%, respectively) and MVC compared with CTRL (-28% vs. -45%, respectively). Rate of perceived exertion (RPE) was significantly increased at the initial stages (20-40-60%) of the TTF in DOMS+ST compared with all conditions. These findings indicate that activation of mechanosensitive and mechanonociceptive afferents of a muscle with DOMS reduces TTF of the contralateral homologous exercising limb, in part, by reducing VA, thereby accelerating mechanisms of central fatigue.NEW & NOTEWORTHY We found that activation of mechanosensitive and nociceptive nerve afferents of a rested muscle group experiencing delayed onset muscle soreness was associated with reduced exercise performance of the homologous exercising muscles of the contralateral limb. This occurred with lower muscle voluntary activation of the exercising muscle at the point of task failure.

Decrements of mobility and power in recreationally active septuagenarians is related to loss of force, but not slowing of the muscle: a 5-year longitudinal study.

A lesser 6-min walk distance (6MWD) and timed up-and-go (TUG) in old compared with young adults was previously linked to slowing of muscle contractile properties. The purpose of the present study was to determine whether any further reductions in 6MWD and TUG over a 5-year period in septuagenarians are associated with further slowing of muscle contractile properties. We measured muscle function by a countermovement jump, isometric maximal knee extensor strength (MVC) on a dynamometer and quadriceps muscle size by magnetic resonance imaging (MRI) in 17 older women (71.1 ± 2.8 y) and 17 older men (71.3 ± 4.1y). Performance in TUG and 6MWD were reduced over the 5-year period, irrespective of sex (P < 0.001), and both were correlated with power at both baseline and follow-up (R ≥ 0.53; P ≤ 0.001). Jump take-off velocity (VCMJ) was slower at follow-up (P < 0.01) and correlated with 6MWD and TUG at both baseline and follow-up in both sexes (R ≥ 0.54; P ≤ 0.001). However, the relationship between 'body mass: maximal muscle force ratio' with VCMJ was not significantly changed, indicating that the lower VCMJ was attributable to muscles working at a higher relative load, hence a lower part of the force-velocity relationship, due to a reduction in MVC (body mass had not changed significantly), rather than slowing of the muscle. The lower VCMJ in women than men (P < 0.001) was likewise attributable to a lower MVC rather than slower contractile properties in women. In conclusion, the decrement in 6MWD and TUG in septuagenarians is due to a loss of muscle mass, rather than further loss of muscle quality.

Effects of exercise induced muscle damage on cardiovascular responses to isometric muscle contractions and post-exercise circulatory occlusion.

PURPOSE: The aim of the present study was to investigate whether exercise-induced muscle damage (EIMD) influences cardiovascular responses to isometric exercise and post-exercise circulatory occlusion (PECO). We hypothesized that EIMD would increase muscle afferent sensitivity and, accordingly, increase blood pressure responses to exercise and PECO. METHODS: Eleven male and nine female participants performed unilateral isometric knee extension at 30% of maximal voluntary contraction (MVC) for 3-min. A thigh cuff was rapidly inflated to 250 mmHg for two min PECO, followed by 3 min recovery. Heart rate and blood pressure were monitored beat-by-beat, with stroke volume and cardiac output estimated from the Modelflow algorithm. Measurements were taken before and 48 h after completing eccentric knee-extension contractions to induce muscle damage (EIMD). RESULTS: EIMD caused 21% decrease in MVC (baseline: 634.6 ± 229.3 N, 48 h: 504.0 ± 160 N), and a 17-fold increase in perceived soreness using a visual-analogue scale (0-100 mm; VASSQ) (both p < 0.001). CV responses to exercise and PECO were not different between pre and post EIMD. However, mean arterial pressure (MAP) was higher during the recovery phase after EIMD (p < 0.05). Significant associations were found between increases in MAP during exercise and VASSQ, Rate of Perceived Exertion (RPE) and Pain after EIMD only (all p < 0.05). CONCLUSION: The MAP correlations with muscle soreness, RPE and Pain during contractions of damaged muscles suggests that higher afferent activity was associated with higher MAP responses to exercise.

Effects of short-term unloading and active recovery on human motor unit properties, neuromuscular junction transmission and transcriptomic profile.

Electrophysiological alterations of the neuromuscular junction (NMJ) and motor unit potential (MUP) with unloading are poorly studied. We aimed to investigate these aspects and the underlying molecular mechanisms with short-term unloading and active recovery (AR). Eleven healthy males underwent a 10-day unilateral lower limb suspension (ULLS) period, followed by 21-day AR based on resistance exercise. Quadriceps femoris (QF) cross-sectional area (CSA) and isometric maximum voluntary contraction (MVC) were evaluated. Intramuscular electromyographic recordings were obtained during 10% and 25% MVC isometric contractions from the vastus lateralis (VL). Biomarkers of NMJ molecular instability (serum c-terminal agrin fragment, CAF), axonal damage (neurofilament light chain) and denervation status were assessed from blood samples and VL biopsies. NMJ and ion channel transcriptomic profiles were investigated by RNA-sequencing. QF CSA and MVC decreased with ULLS. Increased CAF and altered NMJ transcriptome with unloading suggested the emergence of NMJ molecular instability, which was not associated with impaired NMJ transmission stability. Instead, increased MUP complexity and decreased motor unit firing rates were found after ULLS. Downregulation of ion channel gene expression was found together with increased neurofilament light chain concentration and partial denervation. The AR period restored most of these neuromuscular alterations. In conclusion, the human NMJ is destabilized at the molecular level but shows functional resilience to a 10-day unloading period at least at relatively low contraction intensities. However, MUP properties are altered by ULLS, possibly due to alterations in ion channel dynamics and initial axonal damage and denervation. These changes are fully reversed by 21 days of AR. KEY POINTS: We used integrative electrophysiological and molecular approaches to comprehensively investigate changes in neuromuscular integrity and function after a 10-day unilateral lower limb suspension (ULLS), followed by 21 days of active recovery in young healthy men, with a particular focus on neuromuscular junction (NMJ) and motor unit potential (MUP) properties alterations. After 10-day ULLS, we found significant NMJ molecular alterations in the absence of NMJ transmission stability impairment. These findings suggest that the human NMJ is functionally resilient against insults and stresses induced by short-term disuse at least at relatively low contraction intensities, at which low-threshold, slow-type motor units are recruited. Intramuscular electromyography analysis revealed that unloading caused increased MUP complexity and decreased motor unit firing rates, and these alterations could be related to the observed changes in skeletal muscle ion channel pool and initial and partial signs of fibre denervation and axonal damage. The active recovery period restored these neuromuscular changes.

Age-Related Declines in Lower Limb Muscle Function are Similar in Power and Endurance Athletes of Both Sexes: A Longitudinal Study of Master Athletes.

The age-related decline in muscle function, particularly muscle power, is associated with increased risk of important clinical outcomes. Physical activity is an important determinant of muscle function, and different types of physical activity e.g. power-based versus endurance-based exercise appear to have differential effects on muscle power. Cross-sectional studies suggest that participation in power-based exercise is associated with greater muscle power across adulthood but this has not been investigated longitudinally. We recruited eighty-nine male and female power and endurance master athletes (sprint and distance runners respectively, baseline age 35-90y). Using jumping mechanography, we measured lower limb muscle function during a vertical jump including at least two testing sessions longitudinally over 4.5 ± 2.4y. We examined effects of time, discipline (power/endurance) and sex in addition to two- and three-way interactions using linear mixed-effects models. Peak relative power, relative force and jump height, but not Esslingen Fitness Index (indicating peak power relative to sex and age-matched reference data) declined with time. Peak power, force, height and EFI were greater in power than endurance athletes. There were no sex, discipline or sex*discipline interactions with time for any variable, suggesting that changes were similar over time for athletes of both sexes and disciplines. Advantages in lower limb muscle function in power athletes were maintained with time, in line with previous cross-sectional studies. These results suggest that improvements in lower limb function in less active older individuals following power-based training persist with continued adherence, although this requires further investigation in interventional studies.

Associations between childhood and adulthood socioeconomic position and grip strength at age 46 years: findings from the 1970 British Cohort Study.

BACKGROUND: Muscle weakness is a key criterion for important age-related conditions, including sarcopenia and frailty. Research suggests lower childhood socioeconomic position (SEP) may be associated with muscle weakness in later life but there is little evidence on associations in younger adults closer to peak muscle strength. We aimed to examine relationships between indicators of SEP in childhood and adulthood and grip strength at age 46y. METHODS: We examined 7,617 participants from the 1970 British Cohort Study with grip strength measurements at 46y. We used sex-specific linear regression models to test associations between five different indicators of SEP in childhood and adulthood (paternal occupational class and parental education levels at age 5 and own occupational class and education level at age 46) and maximum grip strength. Models were adjusted for birth weight, BMI in childhood and adulthood, adult height, disability in childhood, leisure-time physical activity in childhood and adulthood, sedentary behaviour in childhood and adulthood, occupational activity and smoking at age 46. RESULTS: Among women, lower SEP in childhood and adulthood was associated with weaker grip strength even after adjustments for covariates. For example, in fully-adjusted models, women whose mothers had no qualifications at age five had mean grip strength 0.99 kg (95% CI: -1.65, -0.33) lower than women whose mothers were educated to degree and higher. Among men, lower levels of father's education and both adult SEP indicators were associated with stronger grip. The association between own occupational class and grip strength deviated from linearity; men in skilled-manual occupations (i.e. the middle occupational group) had stronger grip than men in the highest occupational group (Difference in means: 1.33 kg (0.60, 2.06)) whereas there was no difference in grip strength between the highest and lowest occupational groups. Adjustment for occupational activity largely attenuated these associations. CONCLUSION: Findings highlight the need to identify age and sex-specific interventions across life to tackle inequalities in important age-related conditions related to weakness.

The association of elevated blood pressure during ischaemic exercise with sport performance in Master athletes with and without morbidity.

BACKGROUND: An exaggerated exercise blood pressure (BP) is associated with a reduced exercise capacity. However, its connection to physical performance during competition is unknown. AIM: To examine BP responses to ischaemic handgrip exercise in Master athletes (MA) with and without underlying morbidities and to assess their association with athletic performance during the World Master Track Cycling Championships 2019. METHODS: Forty-eight Master cyclists [age 59 ± 13yrs; weekly training volume 10.4 ± 4.1 h/week; handgrip maximum voluntary contraction (MVC) 46.3 ± 11.5 kg] divided into 2 matched groups (24 healthy MA and 24 MA with morbidity) and 10 healthy middle-aged non-athlete controls (age 48.3 ± 8.3 years; MVC 40.4 ± 14.8 kg) performed 5 min of forearm occlusion including 1 min handgrip isometric contraction (40%MVC) followed by 5 min recovery. Continuous beat-by-beat BP was recorded using finger plethysmography. Age-graded performance (AGP) was calculated to compare race performances among MA. Healthy Master cyclists were further grouped into middle-age (age 46.2 ± 6.4 years; N:12) and old-age (age 65.0 ± 7.7 years; N:12) for comparison with middle-aged non-athlete controls. RESULTS: Healthy and morbidity MA groups showed similar BP responses during forearm occlusion and AGP (90.1 ± 4.3% and 91.0 ± 5.3%, p > 0.05, respectively). Healthy and morbidity MA showed modest correlation between the BP rising slope for 40%MVC ischaemic exercise and AGP (r = 0.5, p < 0.05). MA showed accelerated SBP recovery after cessation of ischaemic handgrip exercise compared to healthy non-athlete controls. CONCLUSION: Our findings associate long-term athletic training with improved BP recovery following ischaemic exercise regardless of age or reported morbidity. Exaggerated BP in Master cyclists during ischaemic exercise was associated with lower AGP during the World Master Cycling Championships.

Sex Comparison of Knee Extensor Size, Strength, and Fatigue Adaptation to Sprint Interval Training.

ABSTRACT: Bagley, L, Al-Shanti, N, Bradburn, S, Baig, O, Slevin, M, and McPhee, JS. Sex comparison of knee extensor size, strength, and fatigue adaptation to sprint interval training. J Strength Cond Res 35(1): 64-71, 2021-Regular sprint interval training (SIT) improves whole-body aerobic capacity and muscle oxidative potential, but very little is known about knee extensor anabolic or fatigue resistance adaptations, or whether effects are similar for men and women. The purpose of this study was to compare sex-related differences in knee extensor size, torque-velocity relationship, and fatigability adaptations to 12-week SIT. Sixteen men and 15 women (mean [SEM] age: 41 [±2.5] years) completed measurements of total body composition assessed by dual energy X-ray absorptiometry, quadriceps muscle cross-sectional area (CSAQ) assessed by magnetic resonance imaging, the knee extensor torque-velocity relationship (covering 0-240°·s-1) and fatigue resistance, which was measured as the decline in torque from the first to the last of 60 repeated concentric knee extensions performed at 180°·s-1. Sprint interval training consisted of 4 × 20-second sprints on a cycle ergometer set at an initial power output of 175% of power at V̇o2max, 3 times per week for 12 weeks. Quadriceps muscle cross-sectional area increased by 5% (p = 0.023) and fatigue resistance improved 4.8% (p = 0.048), with no sex differences in these adaptations (sex comparisons: p = 0.140 and p = 0.282, respectively). Knee extensor isometric and concentric torque was unaffected by SIT in both men and women (p > 0.05 for all velocities). Twelve-week SIT, totaling 4 minutes of very intense cycling per week, significantly increased fatigue resistance and CSAQ similarly in men and women, but did not significantly increase torque in men or women. These results suggest that SIT is a time-effective training modality for men and women to increase leg muscle size and fatigue resistance.

Targeted genotype analyses of GWAS-derived lean body mass and handgrip strength-associated single-nucleotide polymorphisms in elite master athletes.

Recent large genome-wide association studies (GWAS) have independently identified a set of genetic loci associated with lean body mass (LBM) and handgrip strength (HGS). Evaluation of these candidate single-nucleotide polymorphisms (SNPs) may be useful to investigate genetic traits of populations at higher or lower risk of muscle dysfunction. As such, we investigated associations between six SNPs linked to LBM or HGS in a population of elite master athletes (MA) and age-matched controls as a representative population of older individuals with variable maintenance of muscle mass and function. Genomic DNA was isolated from buffy coat samples of 96 individuals [consisting of 48 MA (71 ± 6 yr, age-graded performance 83 ± 9%) and 48 older controls (75 ± 6 yr)]. SNP validation and sample genotyping were conducted using the tetra-primer amplification refractory mutation system (ARMS). For the three SNPs analyzed that were previously associated with LBM (FTO, IRS1, and ADAMTSL3), multinomial logistic regression revealed a significant association of the ADAMTSL3 genotype with %LBM (P < 0.01). For the three HGS-linked SNPs, neither GBF1 nor GLIS1 showed any association with HGS, but for TGFA, multinomial logistic regression revealed a significant association of genotype with HGS (P < 0.05). For ADAMTSL3, there was an enrichment of the effect allele in the MA (P < 0.05, Fisher's exact test). Collectively, of the six SNPs analyzed, ADAMTSL3 and TGFA showed significant associations with LBM and HGS, respectively. The functional relevance of the ADAMTSL3 SNP in body composition and of TGFA in strength may highlight a genetic component of the elite MA phenotype.

Absence of an aging-related increase in fiber type grouping in athletes and non-athletes.

The aging-related loss of muscle mass is thought to be partly attributable to motor neuron loss and motor unit remodeling that result in fiber type grouping. We examined fiber type grouping in 19- to 85-year-old athletes and non-athletes and evaluated to which extent any observed grouping is explained by the fiber type composition of the muscle. Since regular physical activity may stimulate reinnervation, we hypothesized that fiber groups are larger in master athletes than in age-matched non-athletes. Fiber type grouping was assessed in m. vastus lateralis biopsies from 22 young (19-27 years) and 35 healthy older (66-82 years) non-athletes, and 14 young (20-29 years), 51 middle-aged (38-65 years), and 31 older (66-85 years) athletes. An "enclosed fiber" was any muscle fiber of a particular type surrounded by fibers of the same type only. A fiber type group was defined as a group of fibers with at least one enclosed fiber. Only type II fiber cross-sectional area (FCSA) showed an age-related decline that was greater in athletes (P < .001) than in non-athletes (P = .012). There was no significant age-related effect on fiber group size or fiber group number in athletes or non-athletes, and the observed grouping was similar to that expected from the fiber type composition. At face value, these observations do 1) neither show evidence for an age-related loss and remodeling of motor units nor 2) improved reinnervation with regular physical activity, but 3) histological examination may not reveal the full extent of aging-related motor unit remodeling.

Five-year longitudinal changes in thigh muscle mass of septuagenarian men and women assessed with DXA and MRI.

Magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA) were used to assess changes in thigh lean mass in septuagenarian men and women during a 5-year longitudinal study. Twenty-four older individuals participated in the study (10 men: 71.6 ± 4.1 years; 14 women: 71.3 ± 3.2 years at baseline). Thigh MRI and whole-body DXA scans were used to estimate changes in thigh lean mass. Both MRI and DXA showed that thigh lean mass was reduced by approximately 5% (P = 0.001) over the 5-year period in both men and women. The percentage loss of muscle mass determined with MRI and DXA showed moderate correlation (R2 = 0.466; P < 0.001). Bland-Altman analysis showed that the average change over 5 years of follow-up measured by DXA was only 0.18% greater than MRI, where the limits of agreement between DXA and MRI were ± 10.4%. Baseline thigh lean mass did not predict the percentage loss of thigh lean mass over the 5-year period (R2 = 0.003; P = 0.397), but a higher baseline body fat percentage was associated with a larger loss of thigh muscle mass in men (R2 = 0.677; P < 0.003) but not in women (R2 = 0.073; P < 0.176). In conclusion, (1) DXA and MRI showed a similar percentage loss of muscle mass over a 5-year period in septuagenarian men and women that (2) was independent of baseline muscle mass, but (3) increased with higher baseline body fat percentage in men.

Frailty phenotype and frailty index are associated with distinct neuromuscular electrophysiological characteristics in men.

NEW FINDINGS: What is the central question of this study? Human frailty is characterized by accumulated health complaints, including medical conditions, low physical and psychological function and social components. It is currently unknown whether the condition is associated with neuromuscular changes detectable by electrophysiology obtained from voluntary and involuntary muscle contractions. What is the main finding and its importance? A higher likelihood of frailty was significantly associated with a smaller size of vastus lateralis motor unit potentials during voluntary contractions and smaller compound muscle action potentials generated by electrical stimulation. Importantly, these associations were independent of age and body mass index. ABSTRACT: The purpose of this study was to determine whether neuromuscular electrophysiological characteristics that are known to underlie sarcopenia are also associated with the more complex frailty syndrome. Eighty-six men [mean (SD) age, 74 (8) years] were classed as non-frail (robust), prefrail or frail using criteria from the frailty phenotype (FP) and the frailty index (FI). The femoral nerve was stimulated maximally and the resulting compound muscle action potential amplitude (CMAP) measured over the vastus lateralis. Motor unit potential (MUP) size was assessed during voluntary contractions using intramuscular electromyography (iEMG). Logistic and negative binomial regression models determined relationships between FP and FI with CMAP and MUP sizes before and after adjustments for age and body mass index. Larger CMAP size was associated with a lower likelihood of frailty in fully adjusted models: a 1SD higher level in vastus lateralis CMAP size was associated with a 0.4 (95% confidence interval: 0.2, 0.6; P < 0.01) unit lower FI (40% of the FI range) and more than halving of the odds [odds ratio: 0.43 (95% confidence interval: 0.21, 0.90)] of having a frail/prefrail phenotype. Greater MUP size was also related to lower FI values using unadjusted and fully adjusted models. However, MUP size was not significantly related to FP in any model. Smaller MUPs and a smaller CMAP were significantly associated with a higher likelihood of frailty, independent of age and body mass index. These results relate neuromuscular electrophysiological characteristics to the complex frailty syndrome and identify motor unit remodelling as a possible contributing factor.

Targeting miR-423-5p Reverses Exercise Training-Induced HCN4 Channel Remodeling and Sinus Bradycardia.

RATIONALE: Downregulation of the pacemaking ion channel, HCN4 (hyperpolarization-activated cyclic nucleotide gated channel 4), and the corresponding ionic current, If, underlies exercise training-induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes, and it will be important to understand the underlying processes. OBJECTIVE: To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of microRNAs (miRs) in the repression of HCN4. METHODS AND RESULTS: As in rodents, the intrinsic heart rate was significantly lower in human athletes than in nonathletes, and in all subjects, the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes. Next-generation sequencing and quantitative real-time reverse transcription polymerase chain reaction showed remodeling of miRs in the sinus node of swim-trained mice. Computational predictions highlighted a prominent role for miR-423-5p. Interaction between miR-423-5p and HCN4 was confirmed by a dose-dependent reduction in HCN4 3'-untranslated region luciferase reporter activity on cotransfection with precursor miR-423-5p (abolished by mutation of predicted recognition elements). Knockdown of miR-423-5p with anti-miR-423-5p reversed training-induced bradycardia via rescue of HCN4 and If. Further experiments showed that in the sinus node of swim-trained mice, upregulation of miR-423-5p (intronic miR) and its host gene, NSRP1, is driven by an upregulation of the transcription factor Nkx2.5. CONCLUSIONS: HCN remodeling likely occurs in human athletes, as well as in rodent models. miR-423-5p contributes to training-induced bradycardia by targeting HCN4. This work presents the first evidence of miR control of HCN4 and heart rate. miR-423-5p could be a therapeutic target for pathological sinus node dysfunction in veteran athletes.

Similar relative decline in aerobic and anaerobic power with age in endurance and power master athletes of both sexes.

Lower physical activity levels in old age are thought to contribute to the age-related decline in peak aerobic and anaerobic power. Master athletes maintain high levels of physical activity with advancing age and endurance or power training may influence the extent to which these physical functions decline with advancing age. To investigate, 37-90-year-old power (n = 20, 45% female) and endurance (n = 19, 58% female) master athletes were recruited. Maximal aerobic power was assessed when cycling two-legged (VO2 Peak2-leg ) and cycling one-legged (VO2 Peak1-leg ), while peak jumping (anaerobic) power was assessed by a countermovement jump. Men and women had a similar VO2 Peak2-leg (mL/kg/min, P = 0.138) and similar ratio of VO2 Peak1-leg to VO2 Peak2-leg (P = 0.959) and similar ratio of peak aerobic to anaerobic power (P = 0.261). The VO2 Peak2-leg (mL/kg/min) was 17% (P = 0.022) and the peak rate of fat oxidation (FATmax) during steady-state cycling was 45% higher in endurance than power athletes (P = 0.001). The anaerobic power was 33% higher in power than endurance athletes (P = 0.022). The VO2 Peak1-leg :VO2 Peak2-leg ratio did not differ significantly between disciplines, but the aerobic to anaerobic power ratio was 40% higher in endurance than power athletes (P = 0.002). Anaerobic power, VO2 Peak2-leg , VO2 Peak1-leg , and power at FATmax decreased by around 7%-14% per decade in male and female power and endurance athletes. The cross-sectional data from 37-90-year-old master athletes in the present study indicate that peak anaerobic and aerobic power decline by around 7%-14% per decade and this does not differ between athletic disciplines or sexes.

Structure and function of human muscle fibres and muscle proteome in physically active older men.

KEY POINTS: Loss of muscle mass and strength in the growing population of elderly people is a major health concern for modern societies. This condition, termed sarcopenia, is a major cause of falls and of the subsequent increase in morbidity and mortality. Despite numerous studies on the impact of ageing on individual muscle fibres, the contribution of single muscle fibre adaptations to ageing-induced atrophy and functional impairment is still unsettled. The level of physical function and disuse is often associated with ageing. We studied relatively healthy older adults in order to understand the effects of ageing per se without the confounding impact of impaired physical function. We found that in healthy ageing, structural and functional alterations of muscle fibres occur. Protein post-translational modifications, oxidation and phosphorylation contribute to such alterations more than loss of myosin and other muscle protein content. ABSTRACT: Contradictory results have been reported on the impact of ageing on structure and functions of skeletal muscle fibres, likely to be due to a complex interplay between ageing and other phenomena such as disuse and diseases. Here we recruited healthy, physically and socially active young (YO) and elderly (EL) men in order to study ageing per se without the confounding effects of impaired physical function. In vivo analyses of quadriceps and in vitro analyses of vastus lateralis muscle biopsies were performed. In EL subjects, our results show that (i) quadriceps volume, maximum voluntary contraction isometric torque and patellar tendon force were significantly lower; (ii) muscle fibres went through significant atrophy and impairment of specific force (isometric force/cross-sectional area) and unloaded shortening velocity; (iii) myosin/actin ratio and myosin content in individual muscle fibres were not altered; (iv) the muscle proteome went through quantitative adaptations, namely an up-regulation of the content of several groups of proteins among which were myofibrillar proteins and antioxidant defence systems; (v) the muscle proteome went through qualitative adaptations, namely phosphorylation of several proteins, including myosin light chain-2 slow and troponin T and carbonylation of myosin heavy chains. The present results indicate that impairment of individual muscle fibre structure and function is a major feature of ageing per se and that qualitative adaptations of muscle proteome are likely to be more involved than quantitative adaptations in determining such a phenomenon.

Postural Stability During Standing Balance and Sit-to-Stand in Master Athlete Runners Compared With Nonathletic Old and Young Adults.

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] years), healthy old (age 67 [1] years) and master athlete runners (age 67 [1] years; competing and training for the previous 51 [5] years) using the Microsoft Kinect One. The healthy old had more sway than the healthy young in all balance tasks. The master athletes had similar sway to young athletes 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 the young athletes. The healthy old and master athletes also had less anterio-posterior movement during chair rising compared with young athletes. These results suggest that masters runners are not spared from the age-associated decline in postural stability and may benefit from specific balance training.

Age-dependent motor unit remodelling in human limb muscles.

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.

Physical activity in older age: perspectives for healthy ageing and frailty.

Regular physical activity helps to improve physical and mental functions as well as reverse some effects of chronic disease to keep older people mobile and independent. Despite the highly publicised benefits of physical activity, the overwhelming majority of older people in the United Kingdom do not meet the minimum physical activity levels needed to maintain health. The sedentary lifestyles that predominate in older age results in premature onset of ill health, disease and frailty. Local authorities have a responsibility to promote physical activity amongst older people, but knowing how to stimulate regular activity at the population-level is challenging. The physiological rationale for physical activity, risks of adverse events, societal and psychological factors are discussed with a view to inform public health initiatives for the relatively healthy older person as well as those with physical frailty. The evidence shows that regular physical activity is safe for healthy and for frail older people and the risks of developing major cardiovascular and metabolic diseases, obesity, falls, cognitive impairments, osteoporosis and muscular weakness are decreased by regularly completing activities ranging from low intensity walking through to more vigorous sports and resistance exercises. Yet, participation in physical activities remains low amongst older adults, particularly those living in less affluent areas. Older people may be encouraged to increase their activities if influenced by clinicians, family or friends, keeping costs low and enjoyment high, facilitating group-based activities and raising self-efficacy for exercise.

Cardiovascular, muscular and perceptual contributions to physical fatigue in prevalent kidney transplant recipients.

Physical fatigue is debilitating and common among kidney transplant recipients (KTRs). This study investigated the mechanistic aetiology of physical fatigue in this setting through examinations of muscle mass, muscular and cardiovascular function, and perceived exertion. The incidence of physical fatigue, its association with quality of life (QoL), and the predictors of perceived exertion, were evaluated. This single-centre observational cross-sectional study enrolled 55 KTRs. Muscle mass was quantified using dual-energy x-ray absorptiometry. Muscular function was assessed by jumping mechanography. Cardiovascular function (maximal oxygen consumption and oxygen pulse) was estimated during submaximal exercise testing, with perceived exertion determined using age-adjusted Borg scale-ratings. Physical fatigue was measured using Multi-Dimensional Fatigue Inventory-20. QoL was assessed using Medical Outcomes Study Short Form-36. Demographic, clinical, nutritional, psychosocial and behavioural predictors of perceived exertion were assessed. Of clinical importance, increased perceived exertion was the only independent predictor of physical fatigue (P = 0.001), with no association found between physical fatigue and muscular or cardiovascular parameters. Physical fatigue occurred in 22% of KTRs, and negatively impacted on QoL (P < 0.001). Predictors of heightened perception included anxiety (P < 0.05) and mental fatigue (P < 0.05). Perception is a key determinant of physical fatigue in KTRs, paving the way for future interventions.

Association between osteocalcin and cognitive performance in healthy older adults.

INTRODUCTION: cognitive deterioration and reductions of bone health coincide with increasing age. We examine the relationship between bone composition and plasma markers of bone remodelling with measures of cognitive performance in healthy adults. METHODS: this cross-sectional study included 225 old (52% women, mean age: 74.4 ± 3.3 years) and 134 young (52% women, mean age: 23.4 ± 2.7 years) adult participants from the MyoAge project. Whole body bone mineral density was measured by dual-energy X-ray absorptiometry. Blood analyses included a panel of bone-related peptides (dickkopf-1, osteoprotegerin, osteocalcin (OC), osteopontin, sclerostin, parathyroid hormone and fibroblast growth factor 23), as well as serum calcium and 25-hydroxy vitamin D assays. A selection of cognitive domains (working memory capacity, episodic memory, executive functioning and global cognition) was assessed with a standardised neuropsychological test battery. RESULTS: adjusting for covariates and multiple testing revealed that plasma OC levels were positively associated with measures of executive functioning (ß = 0.444, P < 0.001) and global cognition (ß = 0.381, P = 0.001) in the older women. DISCUSSION: these correlative results demonstrate a positive association between OC, a factor known to regulate bone remodelling, with cognitive performance in older non-demented women. Further work should address possible mechanistic interpretations in humans.