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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]

Background: Despite the growing recognition of the obesity crisis, its rates continue to rise. The current first-line therapies, such as dietary changes, energy restriction, and physical activity, are typically met with poor adherence. Novel nutritional interventions can address the root causes of obesity, including mitochondrial dysfunction, and facilitate weight loss. Objective: The objective of this study was to investigate the effects of a multi-ingredient nutritional supplement designed to facilitate mitochondrial function and metabolic health outcomes over a 12 wk period. Methods: Fifty-five overweight and/or obese participants (age (mean ± SEM): 26 ± 1; body mass index (BMI) (kg/m2): 30.5 ± 0.6) completed this double-blind, placebo-controlled clinical trial. Participants were randomized to 12 wks of daily consumption of multi-ingredient supplement (MIS; n = 28; containing 50 mg forskolin, 500 mg green coffee bean extract, 500 mg green tea extract, 500 mg beet root extract, 400 mg α-lipoic acid, 200 IU vitamin E, and 200 mg CoQ10) or control placebo (PLA, n = 27; containing microcrystalline cellulose) matched in appearance. The co-primary outcomes were bodyweight and fat mass (kg) changes. The secondary outcomes included other body composition measures, plasma markers of obesity, fatty liver disease biomarkers, resting energy metabolism, blood pressure, physical performance, and quality of life. The post-intervention differences between MIS and PLA were examined via ANCOVA which was adjusted for the respective pre-intervention variables. Results: After adjustment for pre-intervention data, there was a significant difference in weight (p < 0.001) and fat mass (p < 0.001) post-intervention between the PLA and MIS treatment arms. Post-intervention weight and fat mass were significantly lower in MIS. Significant post-intervention differences corrected for baseline were found in markers of clinical biochemistry (AST, p = 0.017; ALT, p = 0.008), molecular metabolism (GDF15, p = 0.028), and extracellular vesicle-associated miRNA species miR-122 and miR-34a in MIS (p < 0.05). Conclusions: Following the 12 wks of MIS supplementation, weight and body composition significantly improved, concomitant with improvements in molecular markers of liver health and metabolism. [ABSTRACT FROM AUTHOR]

Objective: Metabolic Syndrome (MetS) affects hundreds of millions of individuals and constitutes a major cause of morbidity and mortality worldwide. Obesity is believed to be at the core of metabolic abnormalities associated with MetS, including dyslipidemia, insulin resistance, fatty liver disease and vascular dysfunction. Although previous studies demonstrate a diverse array of naturally occurring antioxidants that attenuate several manifestations of MetS, little is known about the (i) combined effect of these compounds on hepatic health and (ii) molecular mechanisms responsible for their effect. Methods: We explored the impact of a metabolic enhancer (ME), consisting of 7 naturally occurring antioxidants and mitochondrial enhancing agents, on diet-induced obesity, hepatic steatosis and atherogenic serum profile in mice. Results: Here we show that a diet-based ME supplementation and exercise have similar beneficial effects on adiposity and hepatic steatosis in mice. Mechanistically, ME reduced hepatic ER stress, fibrosis, apoptosis, and inflammation, thereby improving overall liver health. Furthermore, we demonstrated that ME improved HFD-induced pro-atherogenic serum profile in mice, similar to exercise. The protective effects of ME were reduced in proprotein convertase subtilisin/kexin 9 (PCSK9) knock out mice, suggesting that ME exerts it protective effect partly in a PCSK9-dependent manner. Conclusions: Our findings suggest that components of the ME have a positive, protective effect on obesity, hepatic steatosis and cardiovascular risk and that they show similar effects as exercise training. [ABSTRACT FROM AUTHOR]

Radiation exposure is an undeniable health threat encountered in various occupations and procedures. High energy waves in ionizing radiation cause DNA damage and induce reactive oxygen species (ROS) production, which further exacerbate DNA, protein, and lipid damage, increasing risk of mutations. Although endogenous antioxidants such as superoxide dismutase have evolved to upregulate and neutralize ROS, exogenous dietary antioxidants also have the potential to combat ionizing radiation (IR)-induced ROS production. We evaluated a cocktail of ingredients (AOX) purported to have antioxidant and mitochondrial protective properties on the acute effects of IR. We show that IR stimulates DNA damage through phosphorylation of DNA repair proteins in the heart, brain, and liver of mice. AOX showed partial protection in brain and liver, through a lack of significant activation in given repair proteins. In addition, AOX attenuated the IR-induced increase in NF-kβ mRNA and protein expression in brain and liver. Lastly, cytochrome c oxidase complex transcripts were significantly higher in heart and brain following radiation, which was also diminished by prior ingestion of AOX. Together, our findings suggest that a multi-ingredient AOX supplement may attenuate the IR-induced cellular damage response and represents a feasible and cost-effective preventative supplement for at-risk populations of radiation exposure. [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]

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-2] and 15 prediabetic (BMI: 27.3 ± 1.2 kg·m-2) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia (FIO2 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. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: This study interrogated mitochondrial respiratory function and content in skeletal muscle biopsies of healthy adults between 30 and 72 years old with and without uncomplicated type 1 diabetes. Methods: Participants (12 women/nine men) with type 1 diabetes (48 ± 11 years of age), without overt complications, were matched for age, sex, BMI and level of physical activity to participants without diabetes (control participants) (49 ± 12 years of age). Participants underwent a Bergström biopsy of the vastus lateralis to assess mitochondrial respiratory function using high-resolution respirometry and citrate synthase activity. Electron microscopy was used to quantify mitochondrial content and cristae (pixel) density. Results: Mean mitochondrial area density was 27% lower (p = 0.006) in participants with type 1 diabetes compared with control participants. This was largely due to smaller mitochondrial fragments in women with type 1 diabetes (−18%, p = 0.057), as opposed to a decrease in the total number of mitochondrial fragments in men with diabetes (−28%, p = 0.130). Mitochondrial respiratory measures, whether estimated per milligram of tissue (i.e. mass-specific) or normalised to area density (i.e. intrinsic mitochondrial function), differed between cohorts, and demonstrated sexual dimorphism. Mass-specific mitochondrial oxidative phosphorylation (OXPHOS) capacity with the substrates for complex I and complex II (CI + II) was significantly lower (−24%, p = 0.033) in women with type 1 diabetes compared with control participants, whereas mass-specific OXPHOS capacities with substrates for complex I only (pyruvate [CI pyr] or glutamate [CI glu]) or complex II only (succinate [CII succ]) were not different (p > 0.404). No statistical differences (p > 0.397) were found in mass-specific OXPHOS capacity in men with type 1 diabetes compared with control participants despite a 42% non-significant increase in CI glu OXPHOS capacity (p = 0.218). In contrast, intrinsic CI + II OXPHOS capacity was not different in women with type 1 diabetes (+5%, p = 0.378), whereas in men with type 1 diabetes it was 25% higher (p = 0.163) compared with control participants. Men with type 1 diabetes also demonstrated higher intrinsic OXPHOS capacity for CI pyr (+50%, p = 0.159), CI glu (+88%, p = 0.033) and CII succ (+28%, p = 0.123), as well as higher intrinsic respiratory rates with low (more physiological) concentrations of either ADP, pyruvate, glutamate or succinate (p < 0.012). Women with type 1 diabetes had higher (p < 0.003) intrinsic respiratory rates with low concentrations of succinate only. Calculated aerobic fitness (Physical Working Capacity Test [PWC130]) showed a strong relationship with mitochondrial respiratory function and content in the type 1 diabetes cohort. Conclusions/interpretation: In middle- to older-aged adults with uncomplicated type 1 diabetes, we conclude that skeletal muscle mitochondria differentially adapt to type 1 diabetes and demonstrate sexual dimorphism. Importantly, these cellular alterations were significantly associated with our metric of aerobic fitness (PWC130) and preceded notable impairments in skeletal mass and strength. [ABSTRACT FROM AUTHOR]

Muscle satellite cell (SC) regulation is a complex process involving many key signalling molecules. Recently, the neurotrophinbrain-derived neurotropic factor (BDNF) has implicated in SC regulation in animals. To date, little is known regarding the roleof BDNF in human SC function in vivo. Twenty-nine males (age, 21 ± 0.5 years) participated in the study. Muscle biopsies from thethigh 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. Theproportion 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 BDNFexpression in humans in vivo, with BDNF colocalization to SCs increasing during the later stages of proliferation and earlydifferentiation. [ABSTRACT FROM AUTHOR]

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Skeletal muscle satellite cells (SC) play an important role in muscle repair following injury. The regulation of SC activity is governed by myogenic regulatory factors (MRF), including MyoD, Myf5, myogenin, and MRF4. The mRNA expression of these MRF in humans following muscle damage has been predominately measured in whole muscle homogenates. Whether the temporal expression of MRF in a whole muscle homogenate reflects SC-specific expression of MRF remains largely unknown. Sixteen young men (23.1 ± 1.0 yr) performed 300 unilateral eccentric contractions (180°/s) of the knee extensors. Percutaneous muscle biopsies from the vastus lateralis were taken before (Pre) and 48 h postexercise. Fluorescence-activated cell sorting analysis was utilized to purify NCAM+ muscle SC from the whole muscle homogenate. Forty-eight hours post-eccentric exercise, MyoD, Myf5, and myogenin mRNA expression were increased in the whole muscle homogenate (~1.4-, ~4.0-, ~1.7-fold, respectively, P < 0.05) and in isolated SC (~19.3-, ~17.5-, ~58.9-fold, respectively, P < 0.05). MRF4 mRNA expression was not increased 48 h postexercise in the whole muscle homogenate (P > 0.05) or in isolated SC (P > 0.05). In conclusion, our results suggest that the directional changes in mRNA expression of the MRF in a whole muscle homogenate in response to acute eccentric exercise reflects that observed in isolated muscle SC. [ABSTRACT FROM AUTHOR]

Prelaboratory tasks are used to facilitate learning and introduce and provide context for laboratory work. The application of first-person perspective (FPP) technology may provide interesting new approaches to providing prelaboratory preparation. However, there is limited knowledge as to whether this perspective is useful or enjoyable for students preparing for laboratory tasks. The purpose of this study was to examine whether prelaboratory preparation, utilizing the FPP technique, was enjoyable and led to improvements in laboratory task-specific self-efficacy in comparison to the traditional text-only (TO) style. We observed that the FPP group found the style to be generally more enjoyable, entertaining, and generally fun compared with the TO group (5.3 ± 0.2 and 2.7 ± 0.3, respectively, P < 0.05). Furthermore, we found that the FPP group had a greater laboratory task-specific self-efficacy than their counterparts in the TO group, following the prelaboratory preparation (93.6 ± 1.6 and 83.5 ± 3.2, respectively, P < 0.05). We did not find any differences in scenariobased self-efficacy between the FPP and the TO group. Taken together, our data support the use of FPP videos as a novel, refreshing approach to prelaboratory preparation that builds self-efficacy in students performing laboratory tasks. [ABSTRACT FROM AUTHOR]

Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence tryptophan metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults, whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Although exercise training has been shown to improve skeletal muscle mass in older adults, whether this also translates into improvements in transcription factors and metabolites related to the kynurenine pathway has yet to be examined. The aim of the present study was to examine the influence of a 12-wk exercise program on skeletal muscle gene expression of transcription factors, kynurenine aminotransferase (KAT) gene expression, and plasma concentrations of tryptophan metabolites (kynurenines) in healthy older men over 65 yr of age. Exercise training significantly increased skeletal muscle gene expression of transcription factors (peroxisome proliferator-activated receptor-γ coactivator 1α, peroxisome proliferator-activated receptor-α, and peroxisome proliferator-activated receptor-δ: 1.77, 1.99, 2.18-fold increases, respectively, P < 0.01] and KAT isoforms 1–4 (6.5, 2.1, 2.2, and 2.6-fold increases, respectively, P ≤ 0.01). Concentrations of plasma kynurenines were not altered. These results demonstrate that 12 wk of exercise training significantly altered skeletal muscle gene expression of transcription factors and gene expression related to the kynurenine pathway, but not circulating kynurenine metabolites in older men. These findings warrant future research to determine whether distinct exercise modalities or varying intensities could induce a shift in the kynurenine pathway in depressed older adults. [ABSTRACT FROM AUTHOR]

Biological aging is associated with progressive damage accumulation, loss of organ reserves, and systemic inflammation ('inflammaging'), which predispose for a wide spectrum of chronic diseases, including several types of cancer. In contrast, aerobic exercise training (AET) reduces inflammation, lowers all-cause mortality, and enhances both health and lifespan. In this study, we examined the benefits of early-onset, lifelong AET on predictors of health, inflammation, and cancer incidence in a naturally aging mouse model (C57BL/J6). Lifelong, voluntary wheel-running (O-AET; 26-month-old) prevented age-related declines in aerobic fitness and motor coordination vs. age-matched, sedentary controls (O-SED). AET also provided partial protection against sarcopenia, dynapenia, testicular atrophy, and overall organ pathology, hence augmenting the ‘physiologic reserve’ of lifelong runners. Systemic inflammation, as evidenced by a chronic elevation in 17 of 18 pro- and anti-inflammatory cytokines and chemokines (P < 0.05 O-SED vs. 2-month-old Y-CON), was potently mitigated by lifelong AET (P < 0.05 O-AET vs. O-SED), including master regulators of the cytokine cascade and cancer progression (IL-1β, TNF-α, and IL-6). In addition, circulating SPARC, previously known to be upregulated in metabolic disease, was elevated in old, sedentary mice, but was normalized to young control levels in lifelong runners. Remarkably, malignant tumours were also completely absent in the O-AET group, whereas they were present in the brain (pituitary), liver, spleen, and intestines of sedentary mice. Collectively, our results indicate that early-onset, lifelong running dampens inflammaging, protects against multiple cancer types, and extends healthspan of naturally-aged mice. [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]

Background: Nutritional supplementation can have beneficial effects on body composition, strength, and function in older adults. However, whether the response of satellite cells can be altered by nutritional supplementation in older adults remains unknown.Objective: We assessed whether a multi-ingredient protein-based supplement taken over a prolonged period of time could alter the muscle satellite cell response after exercise in older men.Methods: Twenty-seven older men [mean ± SD age: 73 ± 1 y; mean ± SD body mass index (kg/m2): 28 ± 1] participated in a randomized double-blind experiment. Participants were randomly divided into an experimental (EXP) group (n = 13) who consumed a multi-ingredient protein-based supplement [30 g whey protein, 2.5 g creatine, 500 IU vitamin D, 400 mg Ca, and 1500 mg n-3 (ω-3) polyunsaturated fatty acids] 2 times/d for 7 wk or a control (CON; 22 g maltodextrin) group (n = 14). After 7 wk of supplementation, all participants performed a single resistance exercise session, and muscle biopsy samples were taken from the vastus lateralis before and 24 and 48 h after exercise. Immunohistochemistry was used to assess the change in type I and II muscle fiber satellite cell content and activation status of the cells. In addition, mRNA expression of the myogenic regulatory factors was determined by using reverse transcriptase-polymerase chain reaction.Results: In response to the single bout of exercise, type I muscle fiber satellite cell content was significantly increased at 24 h (0.132 ± 0.015 and 0.131 ± 0.011 satellite cells/fiber in CON and EXP groups, respectively) and 48 h (0.126 ± 0.010 and 0.120 ± 0.012 satellite cells/fiber in CON and EXP groups, respectively) compared with pre-exercise (0.092 ± 0.007 and 0.118 ± 0.017 satellite cells/fiber in CON and EXP groups, respectively) muscle biopsy samples (P < 0.01), with no difference between the 2 groups. In both groups, we observed no significant changes in type II muscle fiber satellite cell content after exercise.Conclusion: Ingesting a multi-ingredient protein-based supplement for 7 wk did not alter the type I or II muscle fiber satellite cell response during postexercise recovery in older men. This trial was registered at www.clinicaltrials.gov as NCT02281331. [ABSTRACT FROM AUTHOR]

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Satellite cells (SC) are associated with skeletal muscle remodelling after muscle damage and/or extensive hypertrophy resulting from resistance training (RT). We recently reported that early increases in muscle protein synthesis (MPS) during RT appear to be directed toward muscle damage repair, but MPS contributes to hypertrophy with progressive muscle damage attenuation. However, modulations in acute-chronic SC content with RT during the initial (1st-wk: high damage), early (3rd-wk: attenuated damage), and later (10th-wk: no damage) stages is not well characterized. Ten young men (27 ± 1 y, 23.6 ± 1.0 kg·m-2) underwent 10-wks of RT and muscle biopsies (vastus-lateralis) were taken before (Pre) and post (48h) the 1st (T1), 5th (T2) and final (T3) RT sessions to evaluate fibre type specific SC content, cross-sectional area (fCSA) and myonuclear number by immunohistochemistry. We observed RT-induced hypertrophy after 10-wks of RT (fCSA increased ~16% in type II, P < 0.04; ~8% in type I [ns]). SC content increased 48h post-exercise at T1 (~69% in type I [P = 0.014]; ~42% in type II [ns]), and this increase was sustained throughout RT (pre T2: ~65%, ~92%; pre T3: ~30% [ns], ~87%, for the increase in type I and II, respectively, vs. pre T1 [P < 0.05]). Increased SC content was not coupled with changes in myonuclear number. SC have a more pronounced role in muscle repair during the initial phase of RT than muscle hypertrophy resulted from 10-wks RT in young men. Chronic elevated SC pool size with RT is important providing proper environment for future stresses or larger fCSA increases. [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]

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/Fi) increased in both type I (1.8 ± 0.3 to 2.0 ± 0.3 C/Fi, P < 0.05) and type II (1.7 ± 0.3 to 2.2 ± 0.3 C/Fi, 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. [ABSTRACT FROM AUTHOR]

Hematopoietic stem and progenitor cells are necessary to maintain, repair, and reconstitute the hematopoietic blood cell system. Mobilization of these cells from bone marrow to blood can be greatly increased under certain conditions, one such being exercise. The purpose of this study was to identify the importance of exercise intensity in hematopoietic mobilization, to better understand the mobilization kinetics postexercise, and to determine if exercise is capable of mobilizing several specific populations of hematopoietic cells that have clinical relevance in a transplant setting. Healthy individuals were exercised on a cycle ergometer at 70% of their peak work rate (WRpeak) until volitional fatigue and at 30% of their WRpeak work matched to the 70% WRpeak bout. Blood was collected before, immediately post, and 10, 30, and 60 min postexercise. Total blood cells, hematocrit, and mononuclear cells isolated by density gradient centrifugation were counted. Specific populations of hematopoietic stem cells were analyzed by flow cytometry. Mononuclear cells, CD34+, CD34+/CD38−, CD34+/CD110+, CD3−/CD16+/CD56+, CD11c+/CD123−, and CD11c−/CD123+ cells per millilter of blood increased postexercise. Overall, the 70% WRpeak exercise group showed greater mobilization immediately postexercise, while there was no observable increase in mobilization in the work matched 30% WRpeak exercise group. Mobilization of specific populations of hematopoietic cells mirrored changes in the general mobilization of mononuclear cells, suggesting that exercise serves as a nonspecific mobilization stimulus. Evidently, higher intensity exercise is capable of mobilizing hematopoietic cells to a large extent and immediately postexercise is an ideal time point for their collection. [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]

Sarcopenia is the age-related loss of skeletal muscle mass and strength. Ultimately, sarcopenia results in the loss of independence, which imposes a large financial burden on healthcare systems worldwide. A critical facet of sarcopenia is the diminished ability for aged muscle to regenerate, repair and remodel. Over the years, research has focused on elucidating underlying mechanisms of sarcopenia and the impaired ability of muscle to respond to stimuli with aging. Muscle-specific stem cells, termed satellite cells (SC), play an important role in maintaining muscle health throughout the lifespan. It is well established that SC are essential in skeletal muscle regeneration, and it has been hypothesized that a reduction and/or dysregulation of the SC pool, may contribute to accelerated loss of skeletal muscle mass that is observed with advancing age. The preservation of skeletal muscle tissue and its ability to respond to stimuli may be impacted by reduced SC content and impaired function observed with aging. Aging is also associated with a reduction in capillarization of skeletal muscle. We have recently demonstrated that the distance between type II fibre-associated SC and capillaries is greater in older compared to younger adults. The greater distance between SC and capillaries in older adults may contribute to the dysregulation in SC activation ultimately impairing muscle's ability to remodel and, in extreme circumstances, regenerate. This viewpoint will highlight the importance of optimal SC activation in addition to skeletal muscle capillarization to maximize the regenerative potential of skeletal muscle in older adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The rate of adjustment (τ) of phase II pulmonary O₂ uptake (VO₂p) is slower when exercise transitions are initiated from an elevated baseline work rate (WR) and metabolic rate (MR). In this study, combinations of cycling cadence (40 vs. 90 rpm) and external WR were used to examine the effect of prior MR on τVO₂p.Methods: Eleven young men completed transitions from 20 W (BSL) to 90% lactate threshold, with transitions performed as two steps of equal ∆WR (LS, lower step; US, upper step), while maintaining a cadence of (1) 40 rpm, (2) 90 rpm, and (3) 40 rpm but with the WRs elevated to match the higher VO₂p associated with 90 rpm cycling (40MATCH); transitions lasted 6 min. VO₂p was measured breath-by-breath using mass spectrometry and turbinometry; vastus lateralis muscle deoxygenation [HHb] was measured using near-infrared spectroscopy. VO₂p and HHb responses were modeled using nonlinear least squares regression analysis.Results: VO₂p at BSL, LS and US was similar for 90 rpm and 40MATCH, but greater than in 40 rpm. Compared to 90 rpm, τVO₂p at 40 rpm was shorter (p < 0.05) in LS (18 ± 5 vs. 28 ± 8 s) but not in US (26 ± 8 vs. 33 ± 9 s), and at 40MATCH, τVO₂p was lower (p < 0.05) (19 ± 6 s) in LS but not in US (34 ± 13 s) despite differing external WR and ∆WR.Conclusions: A similar overall adjustment of [HHb] and VO₂p in LS and US across conditions suggested dynamic matching between microvascular blood flow and O₂ utilization. Prior MR (rather than external WR per se) plays a role in the dynamic adjustment of pulmonary (and muscle) VO₂p. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the impact of eccentric exercise-induced muscle damage on the rate of adjustment in muscle deoxygenation and pulmonary O2 uptake (VO(2p)) kinetics during moderate exercise.Methods: Fourteen males (25 ± 3 year; mean ± SD) completed three step transitions to 90 % θL before (Pre), 24 h (Post24) and 48 h after (Post48) eccentric exercise (100 eccentric leg-press repetitions with a load corresponding to 110 % of the participant's concentric 1RM). Participants were separated into two groups: phase II VO(2p) time constant (τVO(2p)) ≤ 25 s (fast group; n = 7) or τVO(2p) > 25 s (slow group; n = 7). VO(2p) and [HHb] responses were modeled as a mono-exponential.Results: In both groups, isometric peak torque (0°/s) at Post24 was decreased compared to Pre (p < 0.05) and remained depressed at Post48 (p < 0.05). τVO(2p) was designed to be different (p < 0.05) at Pre between the Fast (τVO(2p); 19 ± 4 s) and Slow (32 ± 6 s) groups. There were no differences among time points (τVO(2p): Pre, 19 ± 4 s; Post24, 22 ± 3 s; Post48, 20 ± 4 s) in the Fast group. In Slow, there was a speeding (p < 0.05) from the Pre (32 ± 6 s) to the Post24 (25 ± 6) but not Post48 (31 ± 6), resulting in no difference (p > 0.05) between groups at Post24. This reduction of τVO(2p) was concomitant with the abolishment (p < 0.05) of an overshoot in the [HHb]/VO(2p) ratio.Conclusion: We propose that the sped VO(2p) kinetics observed in the Slow group coupled with an improved [HHb]/VO(2p) ratio suggest a better matching of local muscle O2 delivery to O2 utilization following eccentric contractions. [ABSTRACT FROM AUTHOR]

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We investigated the effects of a novel multi-ingredient supplement comprised of polyphenol antioxidants and compounds known to facilitate mitochondrial function and metabolic enhancement (ME) in a mouse model of obesity. In this study, 6-week-old male C57/BL6J mice were placed on a high-fat diet (HFD; ~60% fat) for 6 weeks, with subsequent allocation into experimentalgroups for 4 weeks: HFD control, HFD + ME10 (10 components), HFD + ME7 (7 components), HFD + ME10 + EX, HFD + EX (where '+EX' animals exercised 3 days/week), and chow-fed control. After the intervention, HFD control animals had significantly greater body weight and fat mass. Despite the continuation of HFD, animals supplemented with multi-ingredient ME or who performed exercise training showed an attenuation of fat mass and preservation of lean body mass, which was further enhanced when combined (ME+EX). ME supplementation stimulated the upregulation of white and brown adipose tissue mRNA transcripts associated with mitochondrial biogenesis, browning, fatty acid transport, and fat metabolism. In WAT depots, this was mirrored by mitochodrial oxidative phosphorylation (OXPHOS) protein expression, and increased in vivo fat oxidation measured via CLAMS. ME supplementation also decreased systemic and local inflammation markers. Herein, we demonstrated that novel multi-ingredient nutritional supplements induced significant fat loss independent of physical activity while preserving muscle mass in obese mice. Mechanistically, these MEs appear to act by inducing a browning program in white adipose tissue and decreasing other pathophysiological impairments associated with obesity, including mitochondrial respiration alterations induced by HFD. [ABSTRACT FROM AUTHOR]

Old age is associated with lower physical activity levels, suboptimal protein intake, and desensitization to anabolic stimuli, predisposing for age-related muscle loss (sarcopenia). Although resistance exercise (RE) and protein supplementation partially protect against sarcopenia under controlled conditions, the efficacy of home-based, unsupervised RE (HBRE) and multi-ingredient supplementation (MIS) is largely unknown. In this randomized, placebo-controlled and double-blind trial, we examined the effects of HBRE/MIS on muscle mass, strength, and function in free-living, older men. Thirty-two sedentary men underwent twelve weeks of home-based resistance band training (3 d/week), in combination with daily intake of a novel five-nutrient supplement ('Muscle5'; M5, n = 16, 77.4 ± 2.8 y) containing whey, micellar casein, creatine, vitamin D, and omega-3 fatty acids, or an isocaloric/isonitrogenous placebo (PLA; n = 16, 74.4 ± 1.3 y), containing collagen and sunflower oil. Appendicular and total lean mass (ASM; +3%, TLM; +2%), lean mass to fat ratios (ASM/% body fat; +6%, TLM/% body fat; +5%), maximal strength (grip; +8%, leg press; +17%), and function (5-Times Sit-to-Stand time; −9%) were significantly improved in the M5 group following HBRE/MIS therapy (pre vs. post tests; p < 0.05). Fast-twitch muscle fiber cross-sectional areas of the quadriceps muscle were also significantly increased in the M5 group post intervention (Type IIa; +30.9%, Type IIx, +28.5%, p < 0.05). Sub-group analysis indicated even greater gains in total lean mass in sarcopenic individuals following HBRE/MIS therapy (TLM; +1.65 kg/+3.4%, p < 0.05). We conclude that the Muscle5 supplement is a safe, well-tolerated, and effective complement to low-intensity, home-based resistance exercise and improves lean mass, strength, and overall muscle quality in old age. [ABSTRACT FROM AUTHOR]

Three theoretical models have been proposed to explain lifespan extension resulting from exposure to extreme conditions in microscopic animals: individuals become completely dormant and stop aging, continue to age or age but at a diminished rate. Here we show that the earliest life history stages, embryonic cell divisions, in the tardigrade species Hypsibius dujardini are retarded when eggs are reared at 0 °C. Compared to control specimens reared at 22 °C, juveniles that hatched from eggs exposed to 0 °C for 4 days and returned to 22 °C experienced a three-day lag, indicating that their biological age was less than their chronological age. As cold exposure duration increased (days = 10, 20, 40), incubation period at 22 °C decreased incrementally (days = 3, 2, 1), suggesting that tardigrades involve a threshold-determined, quantum-like, energetic-based system for controlling embryogenesis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on lack of satellite cells during short-term disuse-induced muscle fiber atrophy, published in the previous issue.