Regenerative function of immune system: Modulation of muscle stem cells

Ageing is characterised by progressive deterioration of physiological systems and the loss of skeletal muscle mass is one of the most recognisable, leading to muscle weakness and mobility impairments. This review highlights interactions between the immune system and skeletal muscle stem cells (widely termed satellite cells or myoblasts) to influence satellite cell behaviour during muscle regeneration after injury, and outlines deficits associated with ageing. Resident neutrophils and macrophages in skeletal muscle become activated when muscle fibres are damaged via stimuli (e.g. contusions, strains, avulsions, hyperextensions, ruptures) and release high concentrations of cytokines, chemokines and growth factors into the microenvironment. These localised responses serve to attract additional immune cells which can reach in excess of 1 × 105 immune cell/mm3 of skeletal muscle in order to orchestrate the repair process. T-cells have a delayed response, reaching peak activation roughly 4 days after the initial damage. The cytokines and growth factors released by activated T-cells play a key role in muscle satellite cell proliferation and migration, although the precise mechanisms of these interactions remain unclear. T-cells in older people display limited ability to activate satellite cell proliferation and migration which is likely to contribute to insufficient muscle repair and, consequently, muscle wasting and weakness. If the factors released by T-cells to activate satellite cells can be identified, it may be possible to develop therapeutic agents to enhance muscle regeneration and reduce the impact of muscle wasting during ageing and disease

The lymphocyte secretome from young adults enhances skeletal muscle proliferation and migration, but effects are attenuated in the secretome of older adults.

Older people experience skeletal muscle wasting, in part due to impaired proliferative capacity of quiescent skeletal muscle satellite cells which can be reversed by exposure to young blood. To investigate the role of immune cells in muscle regeneration, we isolated lymphocytes from whole blood of young and older healthy volunteers and cultured them with, or without, anti-CD3/CD28 activators to induce release of cytokines, interleukins, and growth factors into the media. The secreted proteins were collected to prepare a conditioned media, which was subsequently used to culture C2C12 myoblasts. The conditioned media from the activated young lymphocytes increased the rate of proliferation of myoblasts by around threefold (P < 0.005) and caused an approximate fourfold (P < 0.005) increase in migration compared with nonactivated lymphocyte control media. These responses were characterized by minimal myotube formation (2%), low fusion index (5%), low myosin heavy chain content, and substantial migration. In contrast, myoblasts treated with conditioned media from activated old lymphocytes exhibited a high degree of differentiation, and multi-nucleated myotube formation that was comparable to control conditions, thus showing no effect on proliferation or migration of myoblasts. These results indicate that secreted proteins from lymphocytes of young people enhance the muscle cell proliferation and migration, whereas secreted proteins from lymphocytes of older people may contribute to the attenuated skeletal muscle satellite cell proliferation and migration

Comparison of MRI and DXA to measure muscle size and age-related atrophy in thigh muscles

Objectives: Magnetic resonance imaging (MRI) and dual-energy x-ray absorptiometry (DXA) were used to examine the thigh lean mass in young and old men and women. Methods: A whole-body DXA scan was used to estimate thigh lean mass in young (20 men; 22.4±3.1y; 18 women; 22.1±2.0y) and older adults (25 men; 72.3±4.9y; 28 women; 72.0±4.5y). Thigh lean mass deter-mined with a thigh scan on the DXA or full thigh MRI scans were compared. Results: Although the thigh lean mass quantified by DXA and MRI in young and older participants were correlated (R2=0.88; p<0.001) the magnitude of the differences in thigh lean mass between young and old was smaller with DXA than MRI (old vs. young men 79.5±13.1% and 73.4±11.2%; old vs. young women 88.6±11.8% and 79.4±12.3%, respectively). Detailed analysis of MRI revealed 30% smaller quadriceps muscles in the older than young individuals, while the other thigh muscles were only 18% smaller. Conclusions: DXA underestimates the age-related loss of thigh muscle mass in comparison to MRI. The quadriceps muscles were more susceptible to age-related atrophy compared with other thigh muscles

Exemplar-Based Human Action Recognition with Template Matching from a Stream of Motion Capture

Recent works on human action recognition have focused on representing and classifying articulated body motion. These methods require a detailed knowledge of the action composition both in the spatial and temporal domains, which is a difficult task, most notably under real-time conditions. As such, there has been a recent shift towards the exemplar paradigm as an efficient low-level and invariant modelling approach. Motivated by recent success, we believe a real-time solution to the problem of human action recognition can be achieved. In this work, we present an exemplar-based approach where only a single action sequence is used to model an action class. Notably, rotations for each pose are parameterised in Exponential Map form. Delegate exemplars are selected using k-means clustering, where the cluster criteria is selected automatically. For each cluster, a delegate is identified and denoted as the exemplar by means of a similarity function. The number of exemplars is adaptive based on the complexity of the action sequence. For recognition, Dynamic Time Warping and template matching is employed to compare the similarity between a streamed observation and the action model. Experimental results using motion capture demonstrate our approach is superior to current state-of-the-art, with the additional ability to handle large and varied action sequences

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

Morphological alterations of mouse skeletal muscles during early ageing are muscle specific

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

Soluble factors released from activated T-lymphocytes regulate C2C12 myoblast proliferation and cellular signalling, but effects are blunted in the elderly.

The key objective of this work was to investigate the impact of young and old human lymphocyte secretomes on C2C12 myoblasts regeneration. Conditioned media (CMs) were harvested from isolated young and older lymphocytes treated with (activated AC), or without (non-activated NA), anti-CD3/CD28 activators for 4 days. AC conditioned media from older lymphocytes had decreased levels of amphiregulin (367±208pg/ml vs. 904±323pg/ml; p=0.018) and IGF-I (845±88ng/ml vs. 1100±48ng/ml; p=0.032) compared with younger AC. AC older vs younger lymphocytes had reduced expression of CD25 (24.6±5.5%; p=0.0003) and increased expression of FoxP3 (35±15.7%; p=0.032). Treatment of C2C12 myoblasts with young AC resulted in decreased expression of MyoD (0.46±0.12; p=0.004) and Myogenin (0.34±0.05; p=0.010) mRNA, increased activation of MEk1 (724±140 MFI; p=0.001) and ERK1/2 (3768±314 MFI; p=0.001) and a decreased activation of Akt (74.5±4 MFI; p=0.009) and mTOR (61.8±7 MFI; p=0.001) compared with old AC. By contrast, C2C12 myoblasts treated with older AC displayed increased expression of MyoD (0.7±0.08; p=0.004) and Myogenin (0.68±0.05; p=0.010) mRNA, decreased phosphorylation of MEk1 and ERK1/2 (528±80 MFI; p=0.008, and 1141±668 MFI; p=0.001, respectively) and increased Akt/mTOR activation (171±35 MFI; p=0.009, and 184±33 MFI; p=0.001, respectively). These data provide new evidence that differences between older and younger lymphocyte secretomes contribute to differential responses of C2C12 myoblasts in culture

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

Quantifying habitual levels of physical activity according to impact in older people: accelerometry protocol for the VIBE study

Physical activity (PA) may need to produce high impacts to be osteogenic. The aim of this study was to identify threshold(s) for defining high impact PA for future analyses in the VIBE (Vertical Impact and Bone in the Elderly) study, based on home recordings with triaxial accelerometers. Recordings were obtained from 19 Master Athlete Cohort (MAC; mean 67.6 years) and 15 Hertfordshire Cohort Study (HCS; mean 77.7 years) participants. Data cleaning protocols were developed to exclude artifacts. Accelerations expressed in g units were categorized into three bands selected from the distribution of positive Y-axis peak accelerations. Data were available for 6.6 and 4.4 days from MAC and HCS participants respectively, with approximately 14 hr recording daily. Three-fold more 0.5–1.0g impacts were observed in MAC versus HCS, 20-fold more 1.0–1.5g impacts, and 140-fold more impacts ≥ 1.5g. Our analysis protocol successfully distinguishes PA levels in active and sedentary older individuals

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-1 ·min-1 , 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-1 ·min-1 ) 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 indicates that peak anaerobic and aerobic power decline by around 7-14% per decade and this does not differ between athletic disciplines or sexes. This article is protected by copyright. All rights reserved