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PURPOSE: To investigate the modulation of circulating exosome-like extracellular vesicles (ELVs) after 6 weeks of sprint interval training (SIT) at sea-level, 2,000 m, 3,000 m and 4,000 m. METHODS: Thirty trained endurance male athletes (18-35y) participated in a six-week SIT program (30 s all-out sprint, 4 min 30 s recovery; 4-9 repetitions, 2 sessions/week) at sea-level (SL, n = 8), 2,000 m (FiO2 0.167, n = 8), 3,000 m (FiO2 0.145, n = 7) or 4,000 m (FiO2 0.13, n = 7). Venous blood samples were taken before and after the training period. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards. Candidate ELVs miRNAs were quantified by real-time PCR. RESULTS: When the 3 hypoxic groups were analyzed separately, only very minor differences could be detected in the levels of circulating particles, ELVs markers or miRNA. However, the levels of circulating particles increased (+262%) after training when the 3 hypoxic groups were pooled, and tended to increase at sea-level (+65%), with no difference between these two groups. A trend to an increase was observed for the two ELVs markers, TSG101 (+65%) and HSP60 (+441%), at sea-level, but not in hypoxia. Training also seemed to decrease the abundance of miR-23a-3p and to increase the abundance of miR-21-5p in hypoxia but not at sea-level. CONCLUSIONS: A 6-week SIT program tended to increase the basal levels of circulating ELVs when performed at sea-level, but not in hypoxia. In contrast, ELVs miRNA cargo seemed to be modulated in hypoxic conditions only. Further research should explore the potential differences in the origin of ELVs between normoxic and local and systemic hypoxic conditions.

The purpose of this study is to investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Seventeen healthy [body mass index (BMI): 23.5 ± 0.5 kg·m] and 15 prediabetic (BMI: 27.3 ± 1.2 kg·m) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia ([Formula: see text] 14.0%). Venous blood samples were taken before (T0), during (T30), and after (T60) exercise, and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81, and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX, and CD9 was upregulated in skeletal muscle after exercise in normoxia, whereas CD9 and CD81 were downregulated in hypoxia. ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.

Skeletal muscle is maintained and repaired by sub-laminar, Pax7-expressing satellite cells. However, recent mouse investigations have described a second myogenic progenitor population that resides within the myofiber interstitium and expresses the transcription factor Twist2. Twist2-expressing cells exclusively repair and maintain type IIx/b muscle fibers. Currently, it is unknown if Twist2-expressing cells are present in human skeletal muscle and if they function as myogenic progenitors. Here, we perform a combination of single-cell RNA sequencing analysis and immunofluorescence staining to demonstrate the identity and localization of Twist2-expressing cells in human skeletal muscle. Twist2-expressing cells were identified to be anatomically and transcriptionally comparable to fibro-adipogenic progenitors (FAPs) and lack expression of typical satellite cell markers such as Pax7. Comparative analysis revealed that human and mouse Twist2-expressing cells were highly transcriptionally analogous and resided within the same anatomical structures in vivo. Examination of young and aged skeletal muscle biopsy samples revealed that Twist2-positive cells are more prevalent in aged muscle and increase following 12-weeks of resistance exercise training (RET) in humans. However, the quantity of Twist2-positive cells was not correlated with indices of muscle mass or muscle fiber cross-sectional area (CSA) in young or older muscle, and their abundance was surprisingly, negatively correlated with CSA and myonuclear domain size following RET. Taken together, we have identified cells expressing Twist2 in human skeletal muscle which are responsive to aging and exercise. Further examination of their myogenic potential is warranted.

Skeletal muscle satellite cell (SC) function and responsiveness is regulated, in part, through interactions within the niche, in which they reside. Evidence suggests that structural changes occur in the SC niche as a function of aging. In the present study, we investigated the impact of aging on SC niche properties. Muscle biopsies were obtained from the vastus lateralis of healthy young (YM; 21 ± 1 yr; n = 10) and older men (OM; 68 ± 1 yr; n = 16) at rest. A separate group of OM performed a single bout of resistance exercise and additional muscle biopsies were taken 24 and 48 hours post‐exercise; this was performed before and following 12 wks of combined exercise training (OM‐Ex; 73 ± 1; n = 24). Muscle SC niche measurements were assessed using high resolution immunofluorescent confocal microscopy. Type II SC niche laminin thickness was greater in OM (1.86 ± 0.06 µm) as compared to YM (1.55 ± 0.09 µm, P < .05). The percentage of type II‐associated SC that were completely surrounded by laminin was greater in OM (13.6%±4.2%) as compared to YM (3.5%±1.5%; P < .05). In non‐surrounded SC, the proportion of active MyoD+/Pax7+ SC were higher compared to surrounded SC (P < .05) following a single bout of exercise. This “incarceration” of the SC niche by laminin appears with aging and may inhibit SC activation in response to exercise.

The benefits of exercise on health and longevity are well-established, and evidence suggests that these effects are partially driven by a spectrum of bioactive molecules released into circulation during exercise (e.g., exercise factors or 'exerkines'). Recently, extracellular vesicles (EVs), including microvesicles (MVs) and exosomes or exosome-like vesicles (ELVs), were shown to be secreted concomitantly with exerkines. These EVs have therefore been proposed to act as cargo carriers or 'mediators' of intercellular communication. Given these findings, there has been a rapidly growing interest in the role of EVs in the multi-systemic, adaptive response to exercise. This review aims to summarize our current understanding of the effects of exercise on MVs and ELVs, examine their role in the exercise response and long-term adaptations, and highlight the main methodological hurdles related to blood collection, purification, and characterization of ELVs.

Skeletal muscle satellite cell (SC) function and responsiveness is regulated, in part, through interactions within the niche, in which they reside. Evidence suggests that structural changes occur in the SC niche as a function of aging. In the present study, we investigated the impact of aging on SC niche properties. Muscle biopsies were obtained from the vastus lateralis of healthy young (YM; 21 ± 1 yr; n = 10) and older men (OM; 68 ± 1 yr; n = 16) at rest. A separate group of OM performed a single bout of resistance exercise and additional muscle biopsies were taken 24 and 48 hours post‐exercise; this was performed before and following 12 wks of combined exercise training (OM‐Ex; 73 ± 1; n = 24). Muscle SC niche measurements were assessed using high resolution immunofluorescent confocal microscopy. Type II SC niche laminin thickness was greater in OM (1.86 ± 0.06 µm) as compared to YM (1.55 ± 0.09 µm, P < .05). The percentage of type II‐associated SC that were completely surrounded by laminin was greater in OM (13.6%±4.2%) as compared to YM (3.5%±1.5%; P < .05). In non‐surrounded SC, the proportion of active MyoD+/Pax7+ SC were higher compared to surrounded SC (P < .05) following a single bout of exercise. This “incarceration” of the SC niche by laminin appears with aging and may inhibit SC activation in response to exercise.

Muscle satellite cell (SC) regulation is a complex process involving many key signalling molecules. Recently, the neurotrophin brain-derived neurotropic factor (BDNF) has implicated in SC regulation in animals. To date, little is known regarding the role of BDNF in human SC function in vivo. Twenty-nine males (age, 21 ± 0.5 years) participated in the study. Muscle biopsies from the thigh were obtained prior to a bout of 300 maximal eccentric contractions (Pre), and at 6 h, 24 h, 72 h, and 96 h postexercise. BDNF was not detected in any quiescent (Pax7+/MyoD−) SCs across the time-course. BDNF colocalized to 39% ± 5% of proliferating (Pax7+/MyoD+) cells at Pre, which increased to 84% ± 3% by 96 h (P < 0.05). BDNF was only detected in 13% ± 5% of differentiating (Pax7−/MyoD+) cells at Pre, which increased to 67% ± 4% by 96 h (P < 0.05). The number of myogenin+ cells increased 95% from Pre (1.6 ± 0.2 cells/100 myofibres (MF)) at 24 h (3.1 ± 0.3 cells/100 MF) and remained elevated until 96 h (cells/100 MF), P < 0.05. The proportion of BDNF+/myogenin+ cells was 26% ± 0.3% at Pre, peaking at 24 h (49% ± 3%, P < 0.05) and remained elevated at 96 h (P < 0.05). These data are the first to demonstrate an association between SC proliferation and differentiation and BDNF expression in humans in vivo, with BDNF colocalization to SCs increasing during the later stages of proliferation and early differentiation.

Muscle satellite cell (SC) regulation is a complex process involving many key signalling molecules. Recently, the neurotrophin brain-derived neurotropic factor (BDNF) has implicated in SC regulation in animals. To date, little is known regarding the role of BDNF in human SC function in vivo. Twenty-nine males (age, 21 ± 0.5 years) participated in the study. Muscle biopsies from the thigh were obtained prior to a bout of 300 maximal eccentric contractions (Pre), and at 6 h, 24 h, 72 h, and 96 h postexercise. BDNF was not detected in any quiescent (Pax7+/MyoD−) SCs across the time-course. BDNF colocalized to 39% ± 5% of proliferating (Pax7+/MyoD+) cells at Pre, which increased to 84% ± 3% by 96 h (P < 0.05). BDNF was only detected in 13% ± 5% of differentiating (Pax7−/MyoD+) cells at Pre, which increased to 67% ± 4% by 96 h (P < 0.05). The number of myogenin+ cells increased 95% from Pre (1.6 ± 0.2 cells/100 myofibres (MF)) at 24 h (3.1 ± 0.3 cells/100 MF) and remained elevated until 96 h (cells/100 MF), P < 0.05. The proportion of BDNF+/myogenin+ cells was 26% ± 0.3% at Pre, peaking at 24 h (49% ± 3%, P < 0.05) and remained elevated at 96 h (P < 0.05). These data are the first to demonstrate an association between SC proliferation and differentiation and BDNF expression in humans in vivo, with BDNF colocalization to SCs increasing during the later stages of proliferation and early differentiation.

High‐intensity interval training (HIIT) enhances skeletal muscle oxygen delivery and utilization but data are limited regarding fiber‐specific adaptations in humans. We examined the effect of 18 sessions of HIIT (10 × 60‐sec cycling intervals at ~90% HRmax, interspersed by 60‐sec of recovery) over 6 weeks on markers of microvascular density and oxidative capacity in type I and II fibers in healthy but sedentary young women (Age: 26 ± 7 years; BMI: 30 ± 4 kg·m−2; VO2peak: 2.16 ± 0.45 L·m−1). Immunohistochemical analyses of muscle cross sections revealed a training‐induced increase in capillary contacts per fiber in type I fibers (PRE: 4.38 ± 0.37 vs. POST: 5.17 ± 0.80; main effect, P < 0.05) and type II fibers (PRE: 4.24 ± 0.55 vs. POST: 4.92 ± 0.54; main effect, P < 0.05). The capillary‐to‐fiber ratio also increased after training in type I fibers (PRE: 1.53 ± 1.44 vs. POST: 1.88 ± 0.38; main effect, P < 0.05) and type II fibers (PRE: 1.45 ± 0.19 vs. POST: 1.76 ± 0.27; main effect, P < 0.05). Muscle oxidative capacity as reflected by the protein content of cytochrome oxidase IV also increased after training in type I fibers (PRE: 3500 ± 858 vs. POST: 4442 ± 1377 arbitrary units; main effect, P < 0.01) and type II fibers (PRE: 2632 ± 629 vs. POST: 3863 ± 1307 arbitrary units; main effect, P < 0.01). We conclude that short‐term HIIT in previously inactive women similarly increases markers of capillary density and mitochondrial content in type I and type II fibers.

Factors that determine the skeletal muscle satellite cell (SC) response remain incompletely understood. It is known, however, that SC activation status is closely related to the anatomical relationship between SCs and muscle capillaries. We investigated the impact of muscle fibre capillarization on the expansion and activation status of SCs following a muscle‐damaging exercise protocol in healthy young men. Twenty‐nine young men (21 ± 0.5 years) performed 300 unilateral eccentric contractions (180 deg s−1) of the knee extensors. Percutaneous muscle biopsies from the vastus lateralis and blood samples from the antecubital vein were taken prior to (Pre) exercise and at 6, 24, 72 and 96 h of post‐exercise recovery. A comparison was made between subjects who had a relative low mixed muscle capillary‐to‐fibre perimeter exchange index (CFPE; Low group) and high mixed muscle CFPE index (High group) at baseline. Type I and type II muscle fibre size, myonuclear content, capillarization, and SC response were determined via immunohistochemistry. Overall, there was a significant correlation (r = 0.39; P < 0.05) between the expansion of SC content (change in total Pax7+ cells/100 myofibres) 24 h following eccentric exercise and mixed muscle CFPE index. There was a greater increase in activated SCs (MyoD+/Pax7+ cells) in the High as compared to the Low CFPE group 72 h following eccentric exercise (P < 0.05). The current study provides further evidence that muscle fibre capillarization may play an important role in the activation and expansion of the SC pool during the process of skeletal muscle repair.

Satellite cells are indispensable for skeletal muscle repair and regeneration and are associated with muscle growth in humans. Aerobic exercise training results in improved skeletal muscle health also translating to an increase in satellite cell pool activation. We postulate that aerobic exercise improves satellite cell function in skeletal muscle.

High‐intensity interval training (HIIT) enhances skeletal muscle oxygen delivery and utilization but data are limited regarding fiber‐specific adaptations in humans. We examined the effect of 18 sessions of HIIT (10 × 60‐sec cycling intervals at ~90% HRmax, interspersed by 60‐sec of recovery) over 6 weeks on markers of microvascular density and oxidative capacity in type I and II fibers in healthy but sedentary young women (Age: 26 ± 7 years; BMI: 30 ± 4 kg·m−2; VO2peak: 2.16 ± 0.45 L·m−1). Immunohistochemical analyses of muscle cross sections revealed a training‐induced increase in capillary contacts per fiber in type I fibers (PRE: 4.38 ± 0.37 vs. POST: 5.17 ± 0.80; main effect, P < 0.05) and type II fibers (PRE: 4.24 ± 0.55 vs. POST: 4.92 ± 0.54; main effect, P < 0.05). The capillary‐to‐fiber ratio also increased after training in type I fibers (PRE: 1.53 ± 1.44 vs. POST: 1.88 ± 0.38; main effect, P < 0.05) and type II fibers (PRE: 1.45 ± 0.19 vs. POST: 1.76 ± 0.27; main effect, P < 0.05). Muscle oxidative capacity as reflected by the protein content of cytochrome oxidase IV also increased after training in type I fibers (PRE: 3500 ± 858 vs. POST: 4442 ± 1377 arbitrary units; main effect, P < 0.01) and type II fibers (PRE: 2632 ± 629 vs. POST: 3863 ± 1307 arbitrary units; main effect, P < 0.01). We conclude that short‐term HIIT in previously inactive women similarly increases markers of capillary density and mitochondrial content in type I and type II fibers.

Factors that determine the skeletal muscle satellite cell (SC) response remain incompletely understood. It is known, however, that SC activation status is closely related to the anatomical relationship between SCs and muscle capillaries. We investigated the impact of muscle fibre capillarization on the expansion and activation status of SCs following a muscle‐damaging exercise protocol in healthy young men. Twenty‐nine young men (21 ± 0.5 years) performed 300 unilateral eccentric contractions (180 deg s−1) of the knee extensors. Percutaneous muscle biopsies from the vastus lateralis and blood samples from the antecubital vein were taken prior to (Pre) exercise and at 6, 24, 72 and 96 h of post‐exercise recovery. A comparison was made between subjects who had a relative low mixed muscle capillary‐to‐fibre perimeter exchange index (CFPE; Low group) and high mixed muscle CFPE index (High group) at baseline. Type I and type II muscle fibre size, myonuclear content, capillarization, and SC response were determined via immunohistochemistry. Overall, there was a significant correlation (r = 0.39; P < 0.05) between the expansion of SC content (change in total Pax7+ cells/100 myofibres) 24 h following eccentric exercise and mixed muscle CFPE index. There was a greater increase in activated SCs (MyoD+/Pax7+ cells) in the High as compared to the Low CFPE group 72 h following eccentric exercise (P < 0.05). The current study provides further evidence that muscle fibre capillarization may play an important role in the activation and expansion of the SC pool during the process of skeletal muscle repair.

Satellite cells are indispensable for skeletal muscle repair and regeneration and are associated with muscle growth in humans. Aerobic exercise training results in improved skeletal muscle health also translating to an increase in satellite cell pool activation. We postulate that aerobic exercise improves satellite cell function in skeletal muscle.

Skeletal muscle satellite cells (SC) play an important role in muscle adaptation. In untrained individuals, SC content and activation status have been observed to increase in response to a single bout of exercise. Muscle fiber characteristics change considerably when resistance exercise is performed chronically, but whether training status affects the activity of SC in response to a single bout of exercise remains unknown. We examined the changes in SC content and activation status following a single bout of resistance exercise, before and following a 16-wk progressive resistance training (RT) program in 14 young (25 ± 3 yr) men. Before and after RT, percutaneous biopsies from the vastus lateralis muscle were taken before a single bout of resistance exercise and after 24 and 72 h of postexercise recovery. Muscle fiber size, capillarization, and SC response were determined by immunohistochemistry. Following RT, there was a greater activation of SC after 24 h in response to a single bout of resistance exercise (Pre, 1.4 ± 0.3; 24 h, 3.1 ± 0.3 Pax7+/MyoD+ cells per 100 fibers) compared with before RT (Pre, 1.4 ± 0.3; 24 h, 2.2 ± 0.3 Pax7+/MyoD+ cells per 100 fibers, P < 0.05); no difference was observed 72 h postexercise. Following 16 wk of RT, MyoD mRNA expression increased from basal to 24 h after the single bout of exercise ( P < 0.05); this change was not observed before training. Individual capillary-to-fiber ratio (C/F i) increased in both type I (1.8 ± 0.3 to 2.0 ± 0.3 C/F i, P < 0.05) and type II (1.7 ± 0.3 to 2.2 ± 0.3 C/F i, P < 0.05) fibers in response to RT. After RT, enhanced activation of SC in response to resistance exercise is accompanied by increases in muscle fiber capillarization.

Skeletal muscle satellite cells (SC) play an important role in muscle adaptation. In untrained individuals, SC content and activation status have been observed to increase in response to a single bout of exercise. Muscle fiber characteristics change considerably when resistance exercise is performed chronically, but whether training status affects the activity of SC in response to a single bout of exercise remains unknown. We examined the changes in SC content and activation status following a single bout of resistance exercise, before and following a 16-wk progressive resistance training (RT) program in 14 young (25 ± 3 yr) men. Before and after RT, percutaneous biopsies from the vastus lateralis muscle were taken before a single bout of resistance exercise and after 24 and 72 h of postexercise recovery. Muscle fiber size, capillarization, and SC response were determined by immunohistochemistry. Following RT, there was a greater activation of SC after 24 h in response to a single bout of resistance exercise (Pre, 1.4 ± 0.3; 24 h, 3.1 ± 0.3 Pax7+/MyoD+ cells per 100 fibers) compared with before RT (Pre, 1.4 ± 0.3; 24 h, 2.2 ± 0.3 Pax7+/MyoD+ cells per 100 fibers, P < 0.05); no difference was observed 72 h postexercise. Following 16 wk of RT, MyoD mRNA expression increased from basal to 24 h after the single bout of exercise ( P < 0.05); this change was not observed before training. Individual capillary-to-fiber ratio (C/F i) increased in both type I (1.8 ± 0.3 to 2.0 ± 0.3 C/F i, P < 0.05) and type II (1.7 ± 0.3 to 2.2 ± 0.3 C/F i, P < 0.05) fibers in response to RT. After RT, enhanced activation of SC in response to resistance exercise is accompanied by increases in muscle fiber capillarization.

Background Adequate muscle fibre perfusion is critical for the maintenance of muscle mass; it is essential in the rapid delivery of oxygen, nutrients and growth factors to the muscle, stimulating muscle fibre growth. Muscle fibre capillarization is known to decrease substantially with advancing age. However, whether (relative) low muscle fibre capillarization negatively impacts the muscle hypertrophic response following resistance exercise training in older adults is unknown. Methods Twenty‐two healthy older men (71 ± 1 years) performed 24 weeks of progressive resistance type exercise training. To assess the change in muscle fibre characteristics, percutaneous biopsies from the vastus lateralis muscle were taken before and following 12 and 24 weeks of the intervention programme. A comparison was made between participants who had a relatively low type II muscle fibre capillary‐to‐fibre perimeter exchange index (CFPE; LOW group) and high type II muscle fibre CFPE (HIGH group) at baseline. Type I and type II muscle fibre size, satellite cell, capillary content and distance between satellite cells to the nearest capillary were determined by immunohistochemistry. Results Overall, type II muscle fibre size (from 5150 ± 234 to 6719 ± 446 µm2, P < 0.05) and satellite cell content (from 0.058 ± 0.006 to 0.090 ± 0.010 satellite cells per muscle fibre, P < 0.05) had increased significantly in response to 24 weeks of resistance exercise training. However, these improvements where mainly driven by differences in baseline type II muscle fibre capillarization, whereas muscle fibre size (from 5170 ± 390 to 7133 ± 314 µm2, P < 0.05) and satellite cell content (from 0.059 ± 0.009 to 0.102 ± 0.017 satellite cells per muscle fibre, P < 0.05) increased significantly in the HIGH group, no significant changes were observed in LOW group following exercise training. No significant changes in type I and type II muscle fibre capillarization were observed in response to 12 and 24 weeks of resi

Skeletal muscle satellite cells (SC) play an important role in muscle adaptation. In untrained individuals, SC content and activation status have been observed to increase in response to a single bout of exercise. Muscle fiber characteristics change considerably when resistance exercise is performed chronically, but whether training status affects the activity of SC in response to a single bout of exercise remains unknown. We examined the changes in SC content and activation status following a single bout of resistance exercise, before and following a 16-wk progressive resistance training (RT) program in 14 young (25 ± 3 yr) men. Before and after RT, percutaneous biopsies from the vastus lateralis muscle were taken before a single bout of resistance exercise and after 24 and 72 h of postexercise recovery. Muscle fiber size, capillarization, and SC response were determined by immunohistochemistry. Following RT, there was a greater activation of SC after 24 h in response to a single bout of resistance exercise (Pre, 1.4 ± 0.3; 24 h, 3.1 ± 0.3 Pax7+/MyoD+ cells per 100 fibers) compared with before RT (Pre, 1.4 ± 0.3; 24 h, 2.2 ± 0.3 Pax7+/MyoD+ cells per 100 fibers, P < 0.05); no difference was observed 72 h postexercise. Following 16 wk of RT, MyoD mRNA expression increased from basal to 24 h after the single bout of exercise ( P < 0.05); this change was not observed before training. Individual capillary-to-fiber ratio (C/F i) increased in both type I (1.8 ± 0.3 to 2.0 ± 0.3 C/F i, P < 0.05) and type II (1.7 ± 0.3 to 2.2 ± 0.3 C/F i, P < 0.05) fibers in response to RT. After RT, enhanced activation of SC in response to resistance exercise is accompanied by increases in muscle fiber capillarization.

Background Adequate muscle fibre perfusion is critical for the maintenance of muscle mass; it is essential in the rapid delivery of oxygen, nutrients and growth factors to the muscle, stimulating muscle fibre growth. Muscle fibre capillarization is known to decrease substantially with advancing age. However, whether (relative) low muscle fibre capillarization negatively impacts the muscle hypertrophic response following resistance exercise training in older adults is unknown. Methods Twenty‐two healthy older men (71 ± 1 years) performed 24 weeks of progressive resistance type exercise training. To assess the change in muscle fibre characteristics, percutaneous biopsies from the vastus lateralis muscle were taken before and following 12 and 24 weeks of the intervention programme. A comparison was made between participants who had a relatively low type II muscle fibre capillary‐to‐fibre perimeter exchange index (CFPE; LOW group) and high type II muscle fibre CFPE (HIGH group) at baseline. Type I and type II muscle fibre size, satellite cell, capillary content and distance between satellite cells to the nearest capillary were determined by immunohistochemistry. Results Overall, type II muscle fibre size (from 5150 ± 234 to 6719 ± 446 µm2, P < 0.05) and satellite cell content (from 0.058 ± 0.006 to 0.090 ± 0.010 satellite cells per muscle fibre, P < 0.05) had increased significantly in response to 24 weeks of resistance exercise training. However, these improvements where mainly driven by differences in baseline type II muscle fibre capillarization, whereas muscle fibre size (from 5170 ± 390 to 7133 ± 314 µm2, P < 0.05) and satellite cell content (from 0.059 ± 0.009 to 0.102 ± 0.017 satellite cells per muscle fibre, P < 0.05) increased significantly in the HIGH group, no significant changes were observed in LOW group following exercise training. No significant changes in type I and type II muscle fibre capillarization were observed in response to 12 and 24 weeks of resi

Skeletal muscle possesses the ability to regenerate after injury, but this ability is impaired or delayed with aging. Regardless of age, muscle retains the ability to positively respond to stimuli, such as exercise. We examined whether exercise is able to improve regenerative response in skeletal muscle of aged mice. Twenty‐two‐month‐old male C57Bl/6J mice (n = 20) underwent an 8‐wk progressive exercise training protocol [old exercised (O‐Ex) group]. An old sedentary (O‐Sed) and a sedentary young control (Y‐Ctl) group were included. Animals were subjected to injections of cardiotoxin into the tibialis anterior muscle. The tibialis anterior were harvested before [O‐Ex/O‐Sed/ Y‐Ctl control (CTL); n = 6], 10 d (O‐Ex/O‐Sed/Y‐Ctl d 10; n = 8), and 28 d (O‐Ex/O‐Sed/Y‐Ctl d 28; n = 6) postinjection. Average fiber cross‐sectional area was reduced in all groups at d 10 (CTL: O‐Ex: 2499 ± 140; O‐Sed: 2320 ± 165; Y‐Ctl: 2474 ± 269; d 10: O‐Ex: 1191 ± 100; O‐Sed: 1125 ± 99; Y‐Ctl: 1481 ± 167 μm2; P < 0.05), but was restored to control values in O‐Ex and Y‐Ctl groups at d 28 (O‐Ex: 2257 ± 181; Y‐Ctl: 2398 ± 171 μm2; P >0.05). Satellite cell content was greater at CTL in O‐Ex (2.6 ± 0.4 satellite cells/100 fibers) compared with O‐Sed (1.0 ± 0.1% satellite cells/100 fibers; P < 0.05). Exercise conditioning appears to improve ability of skeletal muscle to regenerate after injury in aged mice.—Joanisse, S., Nederveen, J. P., Baker, J. M., Snijders, T., Iacono, C., Parise, G. Exercise conditioning in old mice improves skeletal muscle regeneration. FASEB J. 30, 3256–3268 (2016).

Background Skeletal muscle satellite cells (SC) are instrumental in maintenance of muscle fibres, the adaptive responses to exercise, and there is an age‐related decline in SC. A spatial relationship exists between SC and muscle fibre capillaries. In the present study, we aimed to investigate whether chronologic age has an impact on the spatial relationship between SC and muscle fibre capillaries. Secondly, we determined whether this spatial relationship changes in response to a single session of resistance exercise. Methods Muscle biopsies were obtained from the vastus lateralis of previously untrained young men (YM, 24 ± 3 years; n = 23) and older men (OM, 67 ± 4 years; n = 22) at rest. A subset of YM (n = 9) performed a single bout of resistance exercise, where additional muscle biopsies taken at 24 and 72 h post‐exercise recovery. Skeletal muscle fibre capillarization, SC content, and activation status were assessed using immunofluorescent microscopy of muscle cross sections. Results Type II muscle fibre SC and capillary content was significantly lower in the YM compared with OM (P < 0.05). Furthermore, type II muscle fibre SC were located at a greater distance from the nearest capillary in OM compared with YM (21.6 ± 1.3 vs. 17.0 ± 0.8 µm, respectively; P < 0.05). In response to a single bout of exercise, we observed a significant increase in SC number and activation status (P < 0.05). In addition, activated vs. quiescent SC were situated closer (P < 0.05) to capillaries. Conclusions We demonstrate that there is a greater distance between capillaries and type II fibre‐associated SC in OM as compared with YM. Furthermore, quiescent SC are located significantly further away from capillaries than active SC after single bout of exercise. Our data have implications for how muscle adapts to exercise and how aging may affect such adaptations.

Background Skeletal muscle satellite cells (SC) are instrumental in maintenance of muscle fibres, the adaptive responses to exercise, and there is an age‐related decline in SC. A spatial relationship exists between SC and muscle fibre capillaries. In the present study, we aimed to investigate whether chronologic age has an impact on the spatial relationship between SC and muscle fibre capillaries. Secondly, we determined whether this spatial relationship changes in response to a single session of resistance exercise. Methods Muscle biopsies were obtained from the vastus lateralis of previously untrained young men (YM, 24 ± 3 years; n = 23) and older men (OM, 67 ± 4 years; n = 22) at rest. A subset of YM (n = 9) performed a single bout of resistance exercise, where additional muscle biopsies taken at 24 and 72 h post‐exercise recovery. Skeletal muscle fibre capillarization, SC content, and activation status were assessed using immunofluorescent microscopy of muscle cross sections. Results Type II muscle fibre SC and capillary content was significantly lower in the YM compared with OM (P < 0.05). Furthermore, type II muscle fibre SC were located at a greater distance from the nearest capillary in OM compared with YM (21.6 ± 1.3 vs. 17.0 ± 0.8 µm, respectively; P < 0.05). In response to a single bout of exercise, we observed a significant increase in SC number and activation status (P < 0.05). In addition, activated vs. quiescent SC were situated closer (P < 0.05) to capillaries. Conclusions We demonstrate that there is a greater distance between capillaries and type II fibre‐associated SC in OM as compared with YM. Furthermore, quiescent SC are located significantly further away from capillaries than active SC after single bout of exercise. Our data have implications for how muscle adapts to exercise and how aging may affect such adaptations.

Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

The purpose of the present studies was to determine the effect of various nonhypertrophic exercise stimuli on satellite cell (SC) pool activity in human skeletal muscle. Previously untrained men and women (men: 29 ± 9 yr and women: 29 ± 2 yr, n = 7 each) completed 6 wk of very low-volume high-intensity sprint interval training. In a separate study, recreationally active men ( n = 16) and women ( n = 3) completed 6 wk of either traditional moderate-intensity continuous exercise ( n = 9, 21 ± 4 yr) or low-volume sprint interval training ( n = 10, 21 ± 2 yr). Muscle biopsies were obtained from the vastus lateralis before and after training. The fiber type-specific SC response to training was determined, as was the activity of the SC pool using immunofluorescent microscopy of muscle cross sections. Training did not induce hypertrophy, as assessed by muscle cross-sectional area, nor did the SC pool expand in any group. However, there was an increase in the number of active SCs after each intervention. Specifically, the number of activated (Pax7+/MyoD+, P ≤ 0.05) and differentiating (Pax7−/MyoD+, P ≤ 0.05) SCs increased after each training intervention. Here, we report evidence of activated and cycling SCs that may or may not contribute to exercise-induced adaptations while the SC pool remains constant after three nonhypertrophic exercise training protocols.

Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

The purpose of the present studies was to determine the effect of various nonhypertrophic exercise stimuli on satellite cell (SC) pool activity in human skeletal muscle. Previously untrained men and women (men: 29 ± 9 yr and women: 29 ± 2 yr, n = 7 each) completed 6 wk of very low-volume high-intensity sprint interval training. In a separate study, recreationally active men ( n = 16) and women ( n = 3) completed 6 wk of either traditional moderate-intensity continuous exercise ( n = 9, 21 ± 4 yr) or low-volume sprint interval training ( n = 10, 21 ± 2 yr). Muscle biopsies were obtained from the vastus lateralis before and after training. The fiber type-specific SC response to training was determined, as was the activity of the SC pool using immunofluorescent microscopy of muscle cross sections. Training did not induce hypertrophy, as assessed by muscle cross-sectional area, nor did the SC pool expand in any group. However, there was an increase in the number of active SCs after each intervention. Specifically, the number of activated (Pax7+/MyoD+, P ≤ 0.05) and differentiating (Pax7−/MyoD+, P ≤ 0.05) SCs increased after each training intervention. Here, we report evidence of activated and cycling SCs that may or may not contribute to exercise-induced adaptations while the SC pool remains constant after three nonhypertrophic exercise training protocols.