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Skeletal muscle adaptations to exercise have been associated with a range of health-related benefits, but cell type-specific adaptations within the muscle are incompletely understood. Here we use single-cell sequencing to determine the effects of exercise on cellular composition and cell type-specific processes in human skeletal muscle before and after intense exercise. Fifteen clusters originating from six different cell populations were identified. Most cell populations remained quantitatively stable after exercise, but a large transcriptional response was observed in mesenchymal, endothelial, and myogenic cells, suggesting that these cells are specifically involved in skeletal muscle remodeling. We found three subpopulations of myogenic cells characterized by different maturation stages based on the expression of markers such as PAX7, MYOD1, TNNI1, and TNNI2. Exercise accelerated the trajectory of myogenic progenitor cells towards maturation by increasing the transcriptional features of fast- and slow-twitch muscle fibers. The transcriptional regulation of these contractile elements upon differentiation was validated in vitro on primary myoblast cells. The cell type-specific adaptive mechanisms induced by exercise presented here contribute to the understanding of the skeletal muscle adaptations triggered by physical activity and may ultimately have implications for physiological and pathological processes affecting skeletal muscle, such as sarcopenia, cachexia, and glucose homeostasis., (© 2022. The Author(s).)

Aim: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP)., Method: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were analyzed with a focused query investigating metabolism- and mitochondria-related gene networks., Results: The mtDNA to genomic DNA ratio was lower in the children with CP compared to the typically developing group (-23%, p=0.002). Out of five investigated complexes in the mitochondrial respiratory chain, we observed lower protein levels of all complexes (I, III, IV, V, -20% to -37%; p<0.05) except complex II. Total peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) messenger RNA (p<0.004), isoforms PGC1α1 (p=0.05), and PGC1α4 (p<0.001) were reduced in CP. Transcriptional similarities were observed between CP, aging, and 90 days' bed rest., Interpretation: Mitochondrial biogenesis, mtDNA, and oxidative phosphorylation protein content are reduced in CP muscle compared with typically developing muscle. Transcriptional pathways shared between aging and long-term unloading suggests metabolic dysregulation in CP, which may guide therapeutic strategies for combatting CP muscle pathology. What this paper adds Cerebral palsy (CP) muscle contains fewer energy-generating organelles than typically developing muscle. Gene expression in CP muscle is similar to aging and long-term bed rest., (© 2021 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

The current study explored whether the marked hypertrophic response noted with a short-term unilateral concurrent exercise paradigm was associated with more prominent changes in myonuclei accretion, ribosome biogenesis, and capillarization compared with resistance exercise alone (RE). Ten men (age 25 ± 4 yr) performed aerobic and resistance exercise (AE + RE) for one leg while the other leg did RE. Muscle biopsies were obtained before and after 5 wk of training and subjected to fiber-type specific immunohistochemical analysis, and quantification of total RNA content and mRNA/rRNA transcript abundance. Type II fiber cross-sectional area (CSA) increased with both AE + RE (22%) and RE (16%), while type I fiber CSA increased mainly with AE + RE (16%). The change score tended to differ between legs for type I CSA ( P = 0.099), and the increase in smallest fiber diameter was greater in AE + RE than RE ( P = 0.029). The number of nuclei per fiber increased after AE + RE in both fiber types, and this increase was greater ( P = 0.027) than after RE. A strong correlation was observed between changes in number of nuclei per fiber and fiber CSA in both fiber types, for both AE + RE and RE ( r > 0.8, P < 0.004). RNA content increased after AE + RE (24%, P = 0.019), but the change-scores did not differ across legs. The capillary variables generally increased in both fiber types, with no difference across legs. In conclusion, the accentuated hypertrophic response to AE + RE was associated with more pronounced myonuclear accretion, which was strongly correlated with the degree of fiber hypertrophy. This suggests that myonuclear accretion could play a role in facilitating muscle hypertrophy also during very short training periods.

This study explored the muscle genome-wide response to long-term unloading (84-day bed rest) in 21 men. We hypothesized that a part of the bed rest-induced gene expression signature would be resilient to a concurrent flywheel resistance exercise (RE) countermeasure. Using DNA microarray technology analyzing 35 345 gene-level probe-sets, we identified 335 annotated probe-sets that were downregulated, and 315 that were upregulated after bed rest (P < .01). Besides a predictable differential expression of genes and pathways related to mitochondria (downregulation; false-discovery rates (FDR) <1E-04), ubiquitin system (upregulation; FDR = 3E-02), and skeletal muscle energy metabolism and structure (downregulation; FDR ≤ 3E-03), 84-day bed rest also altered circadian rhythm regulation (upregulation; FDR = 3E-02). While most of the bed rest-induced changes were counteracted by RE, 209 transcripts were resilient to the exercise countermeasure. Genes upregulated after bed rest were particularly resistant to training (P < .001 vs downregulated, non-reversed genes). Specifically, "Translation Factors," "Proteasome Degradation," "Cell Cycle," and "Nucleotide Metabolism" pathways were not normalized by RE. This study provides an unbiased high-throughput transcriptomic signature of one of the longest unloading periods in humans to date. Classical disuse-related changes in structural and metabolic genes/pathways were identified, together with a novel upregulation of circadian rhythm transcripts. In the context of previous bed rest campaigns, the latter seemed to be related to the duration of unloading, suggesting the transcriptomic machinery continues to adapt throughout extended disuse periods. Despite that the RE training offset most of the bed rest-induced muscle-phenotypic and transcriptomic alterations, we contend that the human skeletal muscle also displays a residual transcriptomic signature of unloading that is resistant to an established exercise countermeasure., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Individuals with cerebral palsy (CP) are less physically active, spend more time sedentary and have lower cardiorespiratory endurance as compared to typically developed individuals. RaceRunning enables high-intensity exercise in individuals with CP with limited or no walking ability, using a three-wheeled running bike with a saddle and a chest plate for support, but no pedals. Training adaptations using this type of exercise are unknown., Methods: Fifteen adolescents/young adults (mean age 16, range 9-29, 7 females/8 males) with CP completed 12 weeks, two sessions/week, of RaceRunning training. Measurements of cardiorespiratory endurance (6-min RaceRunning test (6-MRT), average and maximum heart rate, rate of perceived exertion using the Borg scale (Borg-RPE)), skeletal muscle thickness (ultrasound) of the thigh (vastus lateralis and intermedius muscles) and lower leg (medial gastrocnemius muscle) and passive range of motion (pROM) of hip, knee and ankle were collected before and after the training period., Results: Cardiorespiratory endurance increased on average 34% (6-MRT distance; pre 576 ± 320 m vs. post 723 ± 368 m, p < 0.001). Average and maximum heart rate and Borg-RPE during the 6-MRT did not differ pre vs. post training. Thickness of the medial gastrocnemius muscle increased 9% in response to training (p < 0.05) on the more-affected side. Passive hip flexion increased (p < 0.05) on the less-affected side and ankle dorsiflexion decreased (p < 0.05) on the more affected side after 12 weeks of RaceRunning training., Conclusions: These results support the efficacy of RaceRunning as a powerful and effective training modality in individuals with CP, promoting both cardiorespiratory and peripheral adaptations.

This study aimed to analyse whether increasing the eccentric overload (EO) during resistance training, in terms of range of motion and/or velocity using an electric-motor device, would induce different muscle adaptations than conventional flywheel-EO resistance training. Forty physically active university students (21.7 ± 3.4 years) were randomly placed into one of the three training groups (EX1, EX2, FW) and a control group without training ( n  = 10 per group). Participants in the training groups completed 12 sessions (4 sets of 7 repetitions) of iso-inertial single-leg squat training over 6 weeks for the dominant leg. Resistance was generated either by an electric-motor device at two different velocities for the eccentric phase; 100% (EX1) or 150% (EX2) of concentric speed, or by a conventional flywheel device (FW). Thigh lean tissue mass, unilateral leg press one-repetition maximum (1-RM), unilateral muscle power at different percentages of the 1-RM and bilateral/unilateral vertical jump were assessed before and after the 6-week training. There were significant ( p  < 0.05-0.001) main effects of time in the 3 training groups, indicating increased thigh lean tissue mass (2.5-5.8%), 1-RM load (22.4-30.2%), vertical jump performance (9.1-32.9%) and muscle power (8.8-21.7%), without differences across experimental groups. Participants in the control group did not improve any of the variables measured. In addition, EX2 showed greater gains in eccentric average peak power during training than EX1 and FW ( p  < 0.001). Despite the different EO offered, 6 weeks of resistance training using flywheel or electric-motor devices induced similar significant gains in muscle mass, strength, muscle power and vertical jump.

This study compared the effects of the most frequently employed protocols of flywheel (FW) versus weight-stack (WS) resistance exercise (RE) on regional and muscle-specific adaptations of the knee extensors. Sixteen men ( n = 8) and women ( n = 8) performed 8 weeks (2-3 days/week) of knee extension RE employing FW technology on 1 leg (4 × 7 repetitions), while the contralateral leg performed regular WS training (4 × 8-12 repetitions). Maximal strength (1-repetition maximum (1RM) in WS) and peak FW power were determined before and after training for both legs. Partial muscle volume of vastus lateralis (VL), vastus medialis (VM), vastus intermedius (VI), and rectus femoris (RF) were measured using magnetic resonance imaging. Additionally, quadriceps cross-sectional area was assessed at a proximal and a distal site. There were no differences ( P > 0.05) between FW versus WS in muscle hypertrophy of the quadriceps femoris (8% vs. 9%), VL (10% vs. 11%), VM (6% vs. 8%), VI (5% vs. 5%), or RF (17% vs. 17%). Muscle hypertrophy tended ( P = 0.09) to be greater at the distal compared with the proximal site, but there was no interaction with exercise method. Increases in 1RM and FW peak power were similar across legs, yet the increase in 1RM was greater in men (31%) than in women (20%). These findings suggest that FW and WS training induces comparable muscle-specific hypertrophy of the knee extensors. Given that these robust muscular adaptations were brought about with markedly fewer repetitions in the FW compared with WS, it seems FW training can be recommended as a particularly time-efficient exercise paradigm.

The current study examined the effects of a preceding bout of aerobic exercise (AE) on subsequent molecular signaling to resistance exercise (RE) of the elbow extensors. Eleven men performed unilateral elbow-extensor AE (~45 min at 70% peak workload) followed by unilateral RE (4 × 7 maximal repetitions) for both arms. Thus, one arm performed AE+RE interspersed with 15 min recovery, whereas the other arm conducted RE alone. Muscle biopsies were taken from the triceps brachii of each arm immediately before (PRE) and 15 min (POST1) and 3 h (POST2) after RE. Molecular markers involved in translation initiation, protein breakdown, mechanosignaling, and ribosome biogenesis were analyzed. Peak power during RE was reduced by 24% (±19%) when preceded by AE ( P < 0.05). Increases in PGC1a and MuRF1 expression were greater from PRE to POST2 in AE+RE compared with RE (18- vs. 3.5- and 4- vs. 2-fold, respectively, interaction, P < 0.05). Myostatin mRNA decreased in both arms ( P < 0.05). Phosphorylation of AMPK (Thr 172 ) increased (2.5-fold), and 4E-BP1 (Thr 37/46 ) decreased (2.0-fold), after AE (interactions, P < 0.05). p70 S6K, yes-associated protein, and c-Jun NH 2 -terminal kinase phosphorylation were unaltered, whereas focal adhesion kinase decreased ~1.5-fold, and β 1 -integrin increased ~1.3- to 1.5-fold, (time effect, P < 0.05). Abundance of 45S pre-ribosomal (r)RNA (internally transcribed spacer, ITS ) decreased (~30%) after AE (interaction, P < 0.05), whereas CMYC mRNA was greater in AE+RE compared with RE (12-fold, P < 0.05). POLR1B abundance increased after both AE+RE and RE. All together, our results suggest that a single bout of AE leads to an immediate decrease in signaling for translation initiation and ribosome biogenesis. Yet, this did not translate into altered RE-induced signaling during the 3-h postexercise recovery period.

Satellite cells (SCs) form the resident stem cell population in the skeletal muscle tissue. While their function in mediating tissue regeneration after injury is well described, their role in the undamaged-, aging-, and exercising muscle is only starting to be unraveled. Although direct evidence linking the loss of SC function to the onset of age-related loss of muscle mass and function (i.e., sarcopenia) is currently lacking, satellite cells are increasingly seen as an important component for the decline of tissue function seen with aging. This is evident from the pertinent role of SCs in maintaining homeostasis, and in mediating remodeling- and repair-responses, in the skeletal muscle. This narrative review focuses on human studies, but includes cellular and animal models, to describe the role of SCs in different physiological scenarios relevant for human aging. The intrinsic and extrinsic mechanisms underlying age-induced alterations in the SC pool are discussed, with particular emphasis on the genomic modifications that accumulate in human SCs during a lifetime (i.e., somatic mutation-burden). Finally, the role of exercise as a potential countermeasure to age-induced SC alterations is explored in the different scenarios covered., (© 2019 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this meta-analysis was to examine the effect of flywheel (FW) resistance training with Eccentric Overload (FW-EOT) on muscle size and functional capacities (i.e. strength and power) in athletes and healthy subjects, and to compare FW-induced adaptations with those triggered by traditional resistance exercise interventions., Design: A systematic review and meta-analysis of randomised controlled trials., Methods: A search of electronic databases [PubMed, MEDLINE (SportDiscus), Web of Science, Scopus and PEDro] was conducted to identify all publications employing FW-EOT up to April 30, 2016. Outcomes were analyzed as continuous outcomes using a random effects model to calculate a standardized mean difference (SMD) and 95% CI. A total of 9 studies with 276 subjects and 92 effect sizes met the inclusion criteria and were included in the statistical analyses., Results: The overall pooled estimate from the main effects analysis was 0.63 (95% CI 0.49-0.76) with a significant (p<0.001) Z overall effect of 9.17. No significant heterogeneity (p value=0.78) was found. The meta-analysis showed significant differences between FW-EOT vs. conventional resistance training in concentric and eccentric strength, muscle power, muscle hypertrophy, vertical jump height and running speed, favoring FW-EOT., Conclusions: This meta-analysis provides evidence supporting the superiority of FW-EOT, compared with traditional weight-stack exercise, to promote skeletal muscle adaptations in terms of strength, power and size in healthy subjects and athletes., (Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Exercise load is a key component in determining end-point adaptations to resistance exercise. Yet, there is no information regarding the use of different inertia (i.e., loads) during isoinertial flywheel resistance exercise, a very popular high-intensity training model. Thus, this study examined power, work, force, and eccentric overload produced during flywheel resistance exercise with different inertial settings in men and women. Twenty-two women (n = 11) and men (n = 11) performed unilateral (in both legs) isolated concentric (CON) and coupled CON and eccentric (ECC) exercise in a flywheel knee extension device employing 6 inertias (0.0125, 0.025, 0.0375, 0.05, 0.075, 0.1 kg·m). Power decreased as higher inertias were used, with men showing greater (p ≤ 0.05) decrements than women (-36 vs. -29% from lowest to highest inertia). In contrast, work increased as higher inertias were employed, independent of sex (p ≤ 0.05; ∼48% from lowest to highest inertia). Women increased CON and ECC mean force (46-55%, respectively) more (p ≤ 0.05) than men (34-50%, respectively) from the lowest to the highest inertia evaluated, although the opposite was found for peak force data (i.e., peak force increased more in men than in women as inertia was increased). Men, but not women, increased ECC overload from inertia 0.0125 to 0.0375 kg·m2. Although estimated stretch-shorting cycle use during flywheel exercise was higher (p ≤ 0.05) in men (6.6%) than women (4.9%), values were greater for both sexes when using low-to-medium inertias. The information gained in this study could help athletes and sport and health professionals to better understand the impact of different inertial settings on skeletal muscle responses to flywheel resistance exercise.

As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise, on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n = 9) or without (BR; n = 12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1), and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α), and myostatin, were analyzed in samples from m. vastus lateralis collected before and after bed rest. Activity and gene expression of enzymes controlling oxidative metabolism (CS, SDH) decreased in BR but were partially maintained in BRE. Activity of enzymes regulating anaerobic glycolysis (GPh, PFK-1) was unchanged in BR. Resistance exercise increased the activity of GPh. PGC-1α and VEGF expression decreased in both BR and BRE. Myostatin increased in BR but decreased in BRE after bed rest. The analyses of these unique samples indicate that long-term microgravity induces marked alterations in the oxidative, but not the glycolytic, energy system. The proposed flywheel resistance exercise was effective in counteracting some of the metabolic alterations triggered by 84-day bed rest. Given the disparity between gene expression vs. enzyme activity in several key metabolic markers, posttranscriptional mechanisms should be explored to fully evaluate metabolic adaptations to long-term microgravity with/without exercise countermeasures in human skeletal muscle., (Copyright © 2017 the American Physiological Society.)

Recent reports suggest that aerobic exercise may boost the hypertrophic response to short-term resistance training. This study explored the effects of an acute aerobic exercise bout on the transcriptional response to subsequent resistance exercise. Ten moderately trained men performed ∼45 min cycling on one leg followed by 4 × 7 maximal knee extensions for each leg, 15 min later. Thus, one limb performed aerobic and resistance exercise (AE + RE) while the opposing leg did resistance exercise only (RE). Biopsies were obtained from the vastus lateralis muscle of each leg 3 h after the resistance exercise bout. Using DNA microarray, we analyzed differences [≥1.5-fold, false discovery rate (FDR) ≤10%] in gene expression profiles for the two modes of exercise. There were 176 genes up (127)- or downregulated (49) by AE + RE compared with RE. Among the most significant differentially expressed genes were established markers for muscle growth and oxidative capacity, novel cytokines, transcription factors, and micro-RNAs (miRNAs). The most enriched functional categories were those linked to carbohydrate metabolism and transcriptional regulation. Upstream analysis revealed that vascular endothelial growth factor, cAMP-response element-binding protein, Tet methylcytosine dioxygenase, and mammalian target of rapamycin were regulators highly activated by AE + RE, whereas JnK, NF-κβ, MAPK, and several miRNAs were inhibited. Thus, aerobic exercise alters the skeletal muscle transcriptional signature of resistance exercise to initiate important gene programs promoting both myofiber growth and improved oxidative capacity. These results provide novel insight into human muscle adaptations to diverse exercise modes and offer the very first genomic basis explaining how aerobic exercise may augment, rather than compromise, muscle growth induced by resistance exercise., (Copyright © 2016 the American Physiological Society.)

This study examined the effects of a high-speed power training program in peak muscle power and maximal voluntary isometric contraction (MVIC) of knee extensors in patients with relapsing-remitting multiple sclerosis (MS). Forty patients, 20 women (age 42.8 +/- 10.3 yr) and 20 men (age 44.0 +/- 8.7 yr) diagnosed with relapsing-remitting MS were randomly assigned, with respect to sex, to either an exercise group or a control group. Participants from the exercise group performed 12 wk of supervised muscle power training of knee extensors. All subjects were tested for MVIC and peak muscle power at baseline and after the training intervention. A strain gauge was used to measure the MVIC, and peak muscle power was assessed with a linear encoder at five relative loads. The training-related effects were assessed using a t-test. The results showed no significant changes in the control group from baseline to postintervention evaluation. In contrast, the exercise group significantly increased MVIC (10.8%; p < 0.05) and muscle power at 40, 50, 60, 70, and 80% of the MVIC by 21.8, 14.5, 17.3, 19.4, and 22.3%, respectively (p < 0.01), after the training. These findings suggest that 12 wk of high-speed power training improve both MVIC and muscle power at five different loads in patients with relapsing-remitting MS.

Background: As spaceflight compromises skeletal muscle oxidative and aerobic work capacity, this study assessed the efficacy of resistance exercise (RE) to counteract muscle metabolic perturbations induced by 5 wk unilateral lower limb unloading (UL)., Methods: There were 21 men and women (30-56 yr) who were randomly assigned to either UL with (Group, Grp; UL+RE; N = 10) or without (Grp UL; N = 11) concurrent RE. Iso-inertial RE comprised four sets of seven maximal coupled concentric-eccentric knee extensions executed 2-3 times per week. Percutaneous biopsies were obtained from m. vastus lateralis before and after either intervention. Levels of mRNA expression of factors regulating skeletal muscle oxidative capacity i.e., peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1alpha) and vascular endothelial growth factor (VEGF), and glycolytic capacity, i.e., phosphofructokinase (PFK), glycogen phosphorylase and synthase, hexokinase, and phosphorylase kinase alpha1, were subsequently analyzed., Results: Grp UL showed decreased (36%) PGC-1alpha expression, increased (1.5-fold) PFK expression, and a trend toward decreased VEGF post-intervention. Grp UL+RE showed no changes., Discussion: These results suggest that 5 wk unloading reduces skeletal muscle oxidative capacity and increases glycolytic enzyme activity. More importantly, only 12 bouts of high-force, low-volume resistance exercise attenuated these responses. Thus, the current resistance exercise paradigm emphasizing eccentric overload effectively counteracts unwarranted metabolic alterations induced by 5 wk unloading and may, therefore, aid in maintaining skeletal muscle integrity and endurance, and hence astronaut health and fitness during spaceflight.

Purpose: This study assessed markers of muscle damage and training adaptations to eccentric-overload flywheel resistance exercise (RE) in men and women., Methods: Dynamic strength (1 RM), jump performance, maximal power at different percentages of 1 RM, and muscle mass in three different portions of the thigh were assessed in 16 men and 16 women before and after 6 weeks (15 sessions) of flywheel supine squat RE training. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations were measured before, 24, 48 and 72 h after the first and the last training session., Results: After training, increases in 1 RM were somewhat greater (interaction P < 0.001) in men (25 %) than in women (20 %). Squat and drop jump height and power performance at 50, 60, 70 and 80 % of 1 RM increased after training in both sexes (P < 0.05). Power improvement at 80 % of 1 RM was greater (interaction P < 0.02) in men than women. Muscle mass increased ~5 % in both groups (P < 0.05). CK increased in men after the first training session (P < 0.001), whereas the response in women was unaltered. In both sexes, LDH concentration was greater after the first training session compared with basal values (P < 0.05). After the last session, CK and LDH remained at baseline in both groups., Conclusions: These results suggest that although improvements in maximal strength and power at high loads may be slightly greater for men, eccentric-overload RE training induces comparable and favorable gains in strength, power, and muscle mass in both men and women. Equally important, it appears muscle damage does not interfere with the adaptations triggered by this training paradigm.

This study assessed the effects of a resistance exercise training program on the inflammatory response associated with Toll-like receptor (TLR) 2 and TLR4 signaling pathways in senior participants. Twenty-six healthy subjects (age, 69.5 ± 1.3) were randomized to a training (TG; n = 16) or a control (CG; n = 10) group. TG performed an 8-week resistance training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and levels of proteins involved in the TLR2, TLR4, and myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways were analyzed. The inflammatory status was evaluated through messenger RNA (mRNA) and protein content of interleukin (IL)-10 and tumor necrosis factor alpha (TNF-α) and plasma levels of C-reactive protein (CRP). After the 8-week resistance training, TLR2 and TLR4 protein expression was reduced in TG. MyD88, p65, phospho-p38, TIR domain-containing adaptor inducing interferon (TRIF), IKKi/IKKε, phospho-interferon regulatory factor (IRF) 3, and phosho-IRF7 were also downregulated in TG after the intervention. The training program induced an increase of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Hsp70 and a reduction of Hsp60. While TNF-α mRNA and protein values remained unchanged in both TG and CG, IL-10 mRNA and protein content were upregulated in TG after the intervention. CRP values decreased in TG only. The increase in Hsp70 negatively correlated with TLR2 and TLR4 downregulation. These data suggest that resistance exercise may represent an effective tool to ameliorate the pro-inflammatory status of old participants through an attenuation of MyD88-dependent and MyD88-independent TLR2 and TLR4 signaling pathways.

Background: Although resistance training adaptations in multiple sclerosis (MS) patients have been described, the detraining response in this population is largely unknown., Objective: [corrected] This study was designed to evaluate the effects of a 12-week detraining period on muscle strength (isometric and endurance) and muscle power of multiple sclerosis (MS) patients that had previously carried out a 12-week resistance training program (RTP)., Methods: Forty-two MS patients were randomly assigned into two groups: an exercise group (EG) that performed a 12-week RTP for the knee extensors muscles; and a control group (CG), that did not perform any specific training. Knee extension maximal voluntary isometric contraction (MVIC), muscle power and muscle endurance were evaluated before and after the RTP, as well as 12 weeks after training completion. A strain gauge was used to measure the maximal voluntary isometric contraction and muscle power was assessed with a linear encoder. Muscle endurance was interpreted as the number of repetitions that a patient could perform in a single set of knee extension exercise., Results: The EG increased MVIC and muscle power after the training period, although the training did not affect muscle endurance. After 12 weeks of detraining, MVIC returned to pre-training values but muscle power was still greater than pre-training values in the EG. The CG did not present any change in the variables measured during the intervention., Conclusions: A 12-week RTP improved MVIC and muscle power in MS patients. Additionally, 12 weeks of detraining blunted strength training adaptations in MS patients, although muscle power training adaptations were still evident after the detraining period.

Purpose: This study assessed the influence of an acute aerobic exercise bout on molecular responses to subsequent resistance exercise (RE)., Methods: Nine physically active men performed a 45-min one-legged cycle ergometry exercise and 4 × 7 maximal concentric-eccentric knee extensions for each leg 6 h later. Thus, one limb was subjected to aerobic and resistance exercise (AE+RE), and the contralateral limb to resistance exercise (RE) only. Knee extensor peak power was determined. Biopsies were obtained from the m vastus lateralis before (PRE) and 15 min (POST1) and 3 h after RE. Analysis determined glycogen content, mRNA levels (vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ coactivator-1, muscle RING-finger protein-1, atrogin-1, myostatin), and phosphorylated proteins (mammalian target of rapamycin, p70S6 kinase, ribosomal protein S6, eukaryotic elongation factor 2)., Results: Peak power was similar in AE + RE and RE. After RE, the time course of glycogen utilization and protein signaling was similar across legs. However, phosphorylation of mammalian target of rapamycin and p70S6 kinase was elevated in AE + RE versus RE (main effect, P < 0.05). Vascular endothelial growth factor and peroxisome proliferator-activated receptor-γ coactivator-1 were higher in AE + RE than in RE at PRE and POST1 (P < 0.05). Myostatin was lower in AE + RE versus RE at PRE and POST1 (P < 0.05) and downregulated after resistance exercise only. Atrogin-1 was higher in AE + RE than in RE at PRE and POST1 (P < 0.05) and decreased after RE in AE + RE. Muscle RING-finger protein-1 was similar across legs. No difference for any marker was evident 3 h after RE., Conclusions: These results suggest that acute aerobic exercise alters molecular events regulating muscle protein turnover during the early recovery period from subsequent RE.