Léonard Féasson

Effects of endurance training on satellite cell frequency in skeletal muscle of old men.

We investigated the effects of endurance training on satellite cells, which are a major component of the regenerative capacity of muscles. Muscle biopsies were obtained from the vastus lateralis of 11 men aged between 70 and 80 years who trained for 14 weeks (work load corresponding to 65–95% of peak oxygen consumption, V̇O2 peak). Satellite cells were identified by immunohistochemistry. There was a significant increase in satellite cell number. Additionally, V̇O2 peak, citrate synthase activity, and the area of type IIA fibers were significantly increased. Fiber type distribution and the myonuclear number were not significantly affected. The enhancement of satellite cell frequency and fiber area indicate that endurance training is an efficient strategy to improve muscle function in the elderly. Muscle Nerve 28: 87–92, 2003

Effects of combined lower body endurance and upper body resistance training on the satellite cell pool in elderly subjects

To distinguish the respective potential of endurance and resistance training to increase the satellite cell pool, we investigated the effects of 14 weeks of concurrent lower body endurance and upper body resistance training (3 sessions/week) on vastus lateralis (VLat) and deltoid (Del) muscles of 10 active elderly men. NCAM+ satellite cells and myonuclear number were assessed in VLat and Del. After 14 weeks of training the NCAM+ satellite cell pool increased similarly (+38%) in both muscles, mainly in type II muscle fibers (P < 0.05). There was no significant change in myonuclear number or myonuclear domain in either muscle. Combining resistance training in the upper limbs with endurance training in the lower limbs is an efficient strategy to enhance the satellite cell pool in upper and lower body muscles in elderly subjects. Our results provide a practical reference for the determination of optimal exercise protocols to improve muscle function and regeneration in the elderly. Muscle Nerve, 2008

Neuromuscular Consequences of an Extreme Mountain Ultra-Marathon

We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (−35% [95% CI: −28 to −42%] and −39% [95% CI: −32 to −46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (−19% [95% CI: −7 to −32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144±94 to 13,633±12,626 UI L−1), myoglobin (from 32±22 to 1,432±1,209 µg L−1), and C-Reactive Protein (from <2.0 to 37.7±26.5 mg L−1). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline.

Central and peripheral contributions to neuromuscular fatigue induced by a 24-h treadmill run

This experiment investigated the fatigue induced by a 24-h running exercise (24TR) and particularly aimed at testing the hypothesis that the central component would be the main mechanism responsible for neuromuscular fatigue. Neuromuscular function evaluation was performed before, every 4 h during, and at the end of the 24TR on 12 experienced ultramarathon runners. It consisted of a determination of the maximal voluntary contractions (MVC) of the knee extensors (KE) and plantar flexors (PF), the maximal voluntary activation (%VA) of the KE and PF, and the maximal compound muscle action potential amplitude (Mmax) on the soleus and vastus lateralis. Tetanic stimulations also were delivered to evaluate the presence of low-frequency fatigue and the KE maximal muscle force production ability. Strength loss occurred throughout the exercise, with large changes observed after 24TR in MVC for both the KE and PF muscles (-40.9+/-17.0 and -30.3+/-12.5%, respectively; P<0.001) together with marked reductions of %VA (-33.0+/-21.8 and -14.8+/-18.9%, respectively; P<0.001). A reduction of Mmax amplitude was observed only on soleus, and no low-frequency fatigue was observed for any muscle group. Finally, KE maximal force production ability was reduced to a moderate extent at the end of the 24TR (-10.2%; P<0.001), but these alterations were highly variable (+/-15.7%). These results suggest that central factors are mainly responsible for the large maximal muscle torque reduction after ultraendurance running, especially on the KE muscles. Neural drive reduction may have contributed to the relative preservation of peripheral function and also affected the evolution of the running speed during the 24TR.

Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running

In this study, the coordinated activation of ubiquitin-proteasome pathway (UPP), autophagy-lysosomal pathway (ALP), and mitochondrial remodeling including mitophagy was assessed by measuring protein markers during ultra-endurance running exercise in human skeletal muscle. Eleven male, experienced ultra-endurance athletes ran for 24 h on a treadmill. Muscle biopsy samples were taken from the vastus lateralis muscle 2 h before starting and immediately after finishing exercise. Athletes ran 149.8 ± 16.3 km with an effective running time of 18 h 42 min ( ± 41 min). The phosphorylation state of Akt (-74 ± 5%; P < 0.001), FOXO3a (-49 ± 9%; P < 0.001), mTOR Ser2448 (-32 ± 14%; P = 0.028), and 4E-BP1 (-34 ± 7%; P < 0.001) was decreased, whereas AMPK phosphorylation state increased by 247 ± 170% (P = 0.042). Proteasome β2 subunit activity increased by 95 ± 44% (P = 0.028), whereas the activities associated with the β1 and β5 subunits remained unchanged. MuRF1 protein level increased by 55 ± 26% (P = 0.034), whereas MAFbx protein and ubiquitin-conjugated protein levels did not change. LC3bII increased by 554 ± 256% (P = 0.005), and the form of ATG12 conjugated to ATG5 increased by 36 ± 17% (P = 0.042). The mitochondrial fission marker phospho-DRP1 increased by 110 ± 47% (P = 0.003), whereas the fusion marker Mfn1 and the mitophagy markers Parkin and PINK1 remained unchanged. These results fit well with a coordinated regulation of ALP and UPP triggered by FOXO3 and AMPK during ultra-endurance exercise.

Granulomatous myositis: A clinical study of thirteen cases

Granulomatous myositis (GM) is a rare condition that has generally been described in association with sarcoidosis. In the absence of sarcoidosis or other underlying disease, a diagnosis of isolated GM is considered. Only one study has focused on the clinical difference between isolated GM and sarcoid myopathy (SM). We report 13 cases of symptomatic GM; 8 had sarcoidosis. All patients with sarcoidosis had predominantly proximal, symmetrical lower‐limb weakness, and 3 subsequently developed upper‐limb or distal involvement. Three of the five patients with isolated GM had predominantly distal muscle involvement, and two had dysphagia. Corticosteroid treatment was followed by prolonged improvement in only one patient with sarcoidosis. One patient had acute sarcoid myositis and benefited from methotrexate; other immunosuppressants and etanercept proved ineffective in chronic sarcoid myopathy. Three of the five patients with isolated GM responded to corticosteroid treatment. When last examined, three patients with sarcoidosis had severe disability, whereas patients with isolated GM showed milder weakness. Thus, SM was frequently associated with severe disability and rarely improved after corticosteroid treatment, whereas most patients with isolated GM improved. Muscle Nerve, 2006

Enhancement of microvessel tortuosity in the vastus lateralis muscle of old men in response to endurance training

Muscle microvascularization is usually quantified in transverse sections, in absolute terms (capillaries around fibres, CAF, or capillary‐to‐fibre ratio, C/F) or as CAF related to fibre area (CAF/area, CAFA). The capillary‐to‐fibre perimeter exchange ratio (CFPE) has been introduced in order to assess the role of the capillary‐to‐fibre interface in resistance to O2 diffusion. The ratio between the length of capillaries in contact with fibres and fibre perimeter (LC/PF) has also been used as an index for capillary tortuosity. The possibility of change in capillary tortuosity with endurance training was not considered in previous studies. Consequently, this study investigated the effect of 14 weeks of endurance training on muscle microvascularization, including microvessel tortuosity, in 11 elderly men (8th decade). Microvessels were analysed using the CD31 antibody. Together with the significant increase in peak oxygen exchange and citrate synthase activity, there was a significant increase in C/F. While CFPE and CAFA remained unchanged, an important finding was the clear increase in LC/PF (56%; P < 0.001) for a same sarcomere length. We also found a strong correlation between oxidative enzyme activity and LC/PF both before and after training. These results indicate that endurance training induces significant remodelling in the microvessel network in elderly men and that an increase in the degree of microvessel tortuosity would be an important mechanism of adaptation to endurance training.

Influence of training on NIRS muscle oxygen saturation during submaximal exercise

PURPOSE Endurance training improves the oxygen delivery and muscle metabolism. Muscle oxygen saturation measured by near infrared spectroscopy (IR-SO(2)), which is primarily influenced by the local delivery/demand balance, should thus be modified by training. We examined this effect by determining the influence of change in blood lactate and muscle capillary density with training on IR-SO(2) in seven healthy young subjects. METHODS Two submaximal exercise tests at 50% (Ex1) and 80% pretraining VO(2max) (Ex2) were performed before and after a 4-wk endurance-training program. RESULTS VO(2max) increased only slightly (+8%, NS) with training but the training effect was confirmed by the increased capillary density (+31%, P < 0.01) and citrate synthase activity (50%, P < 0.01), determined from muscle biopsy samples. Before training, blood lactate increased during the first 5 min of Ex1 and then remained constant (3.8 +/- 0.5 mmol x L(-1), P < 0.01), whereas it increased continuously during Ex2 (8.9 +/- 1.8 mmol x L(-1), P < 0.001). After training, lactate decreased significantly and remained constant during the two bouts of exercise (2.0 +/- 0.4 and 3.7 +/- 1.2 at the end of Ex1 and Ex2, respectively, both P < 0.001). During Ex1, IR-SO(2) dropped initially at the onset of exercise and recovered progressively without reaching the resting level. Training did not change this pattern of IR-SO(2). During Ex2, IR-SO(2) decreased progressively during the 15 min of exercise (P < 0.05); IR-SO2 kept constant after the initial drop after training. We found a significant relationship (r = 0.42, P = 0.03) between blood lactate and IR-SO(2) at the end of both bouts of exercise; this relationship was closer before training. By contrast, IR-SO(2) or IR-BV was not related to the capillary density. CONCLUSION The training-induced adaptation in blood lactate influences IR-SO(2) during mild- to hard-intensity exercise. Thus, NIRS could be used as a noninvasive monitoring of training-induced adaptations.

A novel CRYAB mutation resulting in multisystemic disease.

Mutations in the CRYAB gene, encoding alpha-B crystallin, cause distinct clinical phenotypes including isolated posterior polar cataract, myofibrillar myopathy, cardiomyopathy, or a multisystemic disorder combining all these features. Genotype/phenotype correlations are still unclear. To date, multisystemic involvement has been reported only in kindred harboring the R120G substitution. We report a novel CRYAB mutation, D109H, associated with posterior polar cataract, myofibrillar myopathy and cardiomyopathy in a two-generation family with five affected individuals. Age of onset, clinical presentation, and muscle abnormalities were very similar to those described in the R120G family. Alpha-B crystallin may form dimers and acts as a chaperone for a number of proteins. It has been suggested that the phenotypic diversity could be related to the various interactions between target proteins of individual mutant residues. Molecular modeling indicates that residues D109 and R120 interact with each other during dimerization of alpha-B crystallin; interestingly, the two substitutions affecting these residues (D109H and R120G) are associated with the same clinical phenotype, thus suggesting a similar pathogenic mechanism. We propose that impairment of alpha-B crystallin dimerization may also be relevant to the pathogenesis of these disorders.

Physiological and biological factors associated with a 24 h treadmill ultra-marathon performance

The purpose of this study was to examine the physiological and biological factors associated with ultra‐endurance performance. Fourteen male runners volunteered to run on a treadmill as many kilometers as possible over a 24‐h period (24TR). Maximal oxygen uptake (V̇O2max), velocity associated with V̇O2max () and running economy (RE) at 8 km/h were measured. A muscle biopsy was also performed in the vastus lateralis muscle. The subjects ran 149.2 ± 15.7 km in 18 h 39 ± 41 min of effective attendance on the treadmill, corresponding to 39.4 ± 4.2% of . Standard multiple‐regression analysis showed that performance was significantly (R2=0.82; P=0.005) related to V̇O2max and specific endurance, i.e. the average speed sustained over the 24TR expressed in . V̇O2max was associated with a high capillary tortuosity (R2=0.66; P=0.01). Specific endurance was significantly related to RE and citrate synthase activity. It is concluded that a high V̇O2max and an associated developed capillary network are essential for ultra‐endurance running performance. The ability to maintain a high %V̇O2max over a 24TR is another factor associated with performance and is mainly related to RE and high mitochondrial oxidative capacity in the vastus lateralis.