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The age‐related loss of skeletal muscle mass and functionality, known as sarcopenia, is a critical risk factor for morbidity and all‐cause mortality. Resistance exercise training (RET) is the primary countermeasure to fight sarcopenia and ageing. Altered intercellular communication is a hallmark of ageing, which is not well elucidated. Circulating extracellular vesicles (EVs), including exosomes, contribute to intercellular communication by delivering microRNAs (miRNAs), which modulate post‐translational modifications, and have been shown to be released following exercise. There is little evidence regarding how EVs or EV‐miRNAs are altered with age or RET. Therefore, we sought to characterize circulating EVs in young and older individuals, prior to and following a 12‐week resistance exercise programme. Plasma EVs were isolated using size exclusion chromatography and ultracentrifugation. We found that ageing reduced circulating expression markers of CD9, and CD81. Using late‐passage human myotubes as a model for ageing in vitro, we show significantly lower secreted exosome‐like vesicles (ELVs). Further, levels of circulating ELV‐miRNAs associated with muscle health were lower in older individuals at baseline but increased following RET to levels comparable to young. Muscle biopsies show similar age‐related reductions in miRNA expressions, with largely no effect of training. This is reflected in vitro, where aged myotubes show significantly reduced expression of endogenous and secreted muscle‐specific miRNAs (myomiRs). Lastly, proteins associated with ELV and miRNA biogenesis were significantly higher in both older skeletal muscle tissues and aged human myotubes. Together we show that ageing significantly affects ELV and miRNA cargo biogenesis, and release. RET can partially normalize this altered intercellular communication. Key points: We show that ageing reduces circulating expression of exosome‐like vesicle (ELV) markers, CD9 and CD81. Using late‐passage human skeletal myotubes as a model of ageing, we show that secreted ELV markers are significantly reduced in vitro.We find circulating ELV miRNAs associated with skeletal muscle health are lower in older individuals but can increase following resistance exercise training (RET).In skeletal muscle, we find altered expression of miRNAs in older individuals, with no effect of RET.Late‐passage myotubes also appear to have aberrant production of endogenous myomiRs with lower abundance than youthful counterpartsIn older skeletal muscle and late‐passage myotubes, proteins involved with ELV‐ and miRNA biogenesis are upregulated [ABSTRACT FROM AUTHOR]

High aerobic endurance capacity can be acquired by training and/or inherited. Aerobic exercise training (AET) and aging are linked to altered gut microbiome composition, but it is unknown if the environmental stress of exercise and host genetics that predispose for higher exercise capacity have similar effects on the gut microbiome during aging. We hypothesized that exercise training and host genetics would have conserved effects on the gut microbiome across different rodents. We studied young sedentary (Y‐SED, 2‐month‐old) mice, old sedentary (O‐SED, 26‐month‐old) mice, old mice with life‐long AET (O‐AET, 26‐month‐old), and aged rats selectively bred for high (HCR [High Capacity Runner], 21‐month‐old) and low (LCR [Low Capacity Runner], 21‐month‐old) aerobic capacity. Our results showed that O‐SED mice had lower running capacity than Y‐SED mice. The fecal microbiota of O‐SED mice had a higher relative abundance of Lachnospiraceae, Ruminococcaceae, Turicibacteriaceae, and Allobaculum, but lower Bacteroidales, Alistipes, Akkermansia, and Anaeroplasma. O‐AET mice had a higher running capacity than O‐SED mice. O‐AET mice had lower fecal levels of Lachnospiraceae, Turicibacteriaceae, and Allobaculum and higher Anaeroplasma than O‐SED mice. Similar to O‐AET mice, but despite no exercise training regime, aged HCR rats had lower Lachnospiraceae and Ruminococcaceae and expansion of certain Bacteroidales in the fecal microbiome compared to LCR rats. Our data show that environmental and genetic modifiers of high aerobic endurance capacity produce convergent gut microbiome signatures across different rodent species during aging. Therefore, we conclude that host genetics and life‐long exercise influence the composition of the gut microbiome and can mitigate gut dysbiosis and functional decline during aging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Key points: Skeletal muscle stem cells, termed satellite cells, play a crucial role in repair and remodelling of muscle in response to exerciseAn age‐related decline in satellite cell number and/or function has been hypothesized to be a key factor in the development of sarcopenia and/or the blunted muscle fibre adaptive response to prolonged exercise training in older personsWe report that performing prolonged exercise training improves the acute type II muscle fibre satellite cell response following a single bout of resistance exercise in older men.The observed improvement in muscle satellite function is associated with an increase in muscle fibre capillarization following exercise training suggesting a possible functional link between capillarization and satellite cell function. Age‐related type II muscle fibre atrophy is accompanied by a fibre type‐specific decline in satellite cell number and function. Exercise training restores satellite cell quantity in older adults; however, whether it can restore the impaired satellite cell response to exercise in older adults remains unknown. Therefore we assessed the acute satellite cell response to a single exercise session before and after prolonged exercise training in older men. Fourteen older men (74 ± 8 years) participated in a 12‐week exercise training programme (resistance exercise performed twice per week, high intensity interval training once per week). Before and after training, percutaneous biopsies from the vastus lateralis muscle were taken prior to and following 24 and 48 h of post‐exercise recovery. Muscle fibre characteristics were evaluated by immunohistochemistry and mRNA expression by RT‐PCR. Whereas no changes were observed in type II muscle fibres, type I muscle fibre satellite cell content increased significantly at 24 and 48 h after a single bout of resistance exercise before the exercise training programme (P < 0.01). Following the exercise training programme, both type I and type II muscle fibre satellite cell content increased significantly at 24 and 48 h after a single bout of resistance exercise (P < 0.05). The greater acute increase in type II muscle fibre satellite cell content at 24 h post‐exercise recovery after training was correlated with an increase in type II muscle fibre capillarization (r = 0.671, P = 0.012). We show that the acute muscle satellite cell response following exercise can be improved by prolonged exercise training in older men. Key points: Skeletal muscle stem cells, termed satellite cells, play a crucial role in repair and remodelling of muscle in response to exerciseAn age‐related decline in satellite cell number and/or function has been hypothesized to be a key factor in the development of sarcopenia and/or the blunted muscle fibre adaptive response to prolonged exercise training in older personsWe report that performing prolonged exercise training improves the acute type II muscle fibre satellite cell response following a single bout of resistance exercise in older men.The observed improvement in muscle satellite function is associated with an increase in muscle fibre capillarization following exercise training suggesting a possible functional link between capillarization and satellite cell function. [ABSTRACT FROM AUTHOR]

Key points: Skeletal muscle stem cells (satellite cells) play a crucial role in repair and remodelling of muscle in response to exercise. Satellite cells are in close spatial proximity to muscle capillaries and therefore may be influenced by them. In this study, we describe the activation and expansion of the satellite cell pool in response to eccentric contraction‐induced muscle damage in individuals with significantly different levels of muscle capillarization. Individuals with greater capillarization and capacity for muscle perfusion demonstrated enhanced activation and/or expansion of the satellite cell pool allowing for an accelerated recovery of muscle function. These results provide insight into the critical relationship between muscle capillarization and satellite cells during skeletal muscle repair. Abstract: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To investigate the association between muscle fiber capillarization and indices of insulin sensitivity in healthy older adults. A skeletal muscle biopsy was taken from the m. vastus lateralis of 22 healthy (nondiabetic) male older adults. In addition, all participants underwent an Oral Glucose Tolerance Test ( OGTT). Muscle fiber capillarization was assessed by immunohistochemistry. Participants were divided into a group with relatively low ( LOW) or high ( HIGH) muscle fiber capillarization (capillary-to-fiber perimeter exchange ( CFPE) index), based on the median value for the entire group. All participants were healthy, nonobese, and had a normal glucose tolerance, according to the individual OGTT results. Whereas no differences in blood glucose concentrations were observed between groups during the OGTT, the postprandial increase in plasma insulin concentrations was significantly greater in the LOW compared to the HIGH muscle fiber capillarization group ( P < 0.05). Skeletal muscle fiber capillarization may determine insulin sensitivity in humans. [ABSTRACT FROM AUTHOR]

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 resistance exercise training in both the LOW and HIGH group. Conclusions Type II muscle fibre capillarization at baseline may be a critical factor for allowing muscle fibre hypertrophy to occur during prolonged resistance exercise training in older men. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]