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Maintenance of skeletal muscle is essential for health and survival. There are marked losses of skeletal muscle mass as well as strength and physiological function under conditions of low mechanical load, such as space flight, as well as ground based models such as bed rest, immobilization, disuse, and various animal models. Disuse atrophy is caused by mechanical unloading of muscle and this leads to reduced muscle mass without fiber attrition. Skeletal muscle stem cells (satellite cells) and myonuclei are integrally involved in skeletal muscle responses to environmental changes that induce atrophy. Myonuclear domain size is influenced differently in fast and slow twitch muscle, but also by different models of muscle wasting, a factor that is not yet understood. Although the myonuclear domain is 3-dimensional this is rarely considered. Apoptosis as a mechanism for myonuclear loss with atrophy is controversial, whereas cell death of satellite cells has not been considered. Molecular signals such as myostatin/SMAD pathway, MAFbx, and MuRF1 E3 ligases of the ubiquitin proteasome pathway and IGF1-AKT-mTOR pathway are 3 distinctly different contributors to skeletal muscle protein adaptation to disuse. Molecular signaling pathways activated in muscle fibers by disuse are rarely considered within satellite cells themselves despite similar exposure to unloading or low mechanical load. These molecular pathways interact with each other during atrophy and also when various interventions are applied that could alleviate atrophy. Re-applying mechanical load is an obvious method to restore muscle mass, however how nutrient supplementation (e.g., amino acids) may further enhance recovery (or reduce atrophy despite unloading or ageing) is currently of great interest. Satellite cells are particularly responsive to myostatin and to growth factors. Recently, the hibernating squirrel has been identified as an innovative model to study resistance to atrophy. [ABSTRACT FROM AUTHOR]

Introduction: In vivo, daily proanthocyanidolic oligomer (PCO) supplementation before and after experimental skeletal muscle contusion injury has been shown to result in a blunted neutrophil response in tissue, quicker macrophage infiltration into muscle, and faster recovery due to a left shift in time course of inflammation. The current study investigated effects of PCO on circulatory neutrophils and macrophage subpopulations as well as in vitro neutrophil migration. Methods: Primary cultured neutrophils obtained from control animals were incubated in media with 20% conditioned plasma. To obtain conditioned media, male Wistar rats were supplemented with PCO (20 mg•kg−1•d−1) or placebo (PLA) for 2 wk before a mass-drop contusion injury. Conditioned plasma was prepared from blood collected at different time points after injury (12 h, 1 d, 3 d, and 5 d). Macrophage subpopulation distribution, inflammatory cytokine, and myeloperoxidase levels were assessed for all time points. Results: On day 1 postinjury, circulating neutrophil numbers were significantly lower in PLA than PCO, suggesting that extravasation from the blood was reduced by PCO. Concurrently, neutrophil migration in vitro was blunted in the presence of conditioned plasma from PCO supplemented rats compared with PLA supplemented rats. Plasma Ml and M2c macrophage numbers differed over time and between groups. Ml macrophage numbers peaked on day 3 with PCO supplementation, followed by a rise in M2c macrophages on day 5, when Ml macrophages numbers were still high in PLA. Conclusions: We conclude that PCO supplementation limits neutrophil migration capacity in vitro despite a chemotac- tic gradient. Furthermore, the earlier appearance of type M2 macrophages suggests a switch to an anti-inflammatory phenotype after injury even in circulation. [ABSTRACT FROM AUTHOR]

Skeletal muscle protein loss, known as atrophy, occurs during inactivity, disease, and aging. Atrophy may be the result of increased catabolic factors, e.g. glucocorticoids, or reduced influence of anabolic factors, e.g. insulin. The purpose of this study was to investigate atrophy, signaling mechanisms, and apoptosis in a rat model of restraint stress in 40 adult male Wistar rats. Due to the anxiolytic effects of Sutherlandia frutescens, we also determined if any of the molecular events in gastrocnemius muscle would be affected by daily treatment with S. frutescens. Rats were randomly assigned to four experimental groups: control placebo (CP); control Sutherlandia (CS) treatment; Restraint Placebo (RP) and Restraint Sutherlandia (RS) treatment. Restraint resulted in a significant increase in myostatin which was significantly reduced with Sutherlandia treatment. In addition, MyoD expression was significantly attenuated in RP and this effect was also counteracted by Sutherlandia treatment. Restraint also resulted in a significant attenuation of the PI3-Kinase/Akt signaling pathway and increased apoptosis which was reversed with Sutherlandia treatment. This study demonstrates for the first time that psychological stress elevates markers of muscle atrophy and apoptosis, whilst a herbal remedy, Sutherlandia, inhibits apoptosis, and signaling pathways associated with muscle atrophy. [ABSTRACT FROM AUTHOR]

Injury of skeletal muscle, and especially mechanically induced damage such as contusion injury, frequently occurs in contact sports, as well as in accidental contact sports, such as hockey and squash. The large variations with regard to injury severity and affected muscle group, as well as nonspecificity of reported symptoms, complicate research aimed at finding suitable treatments. Therefore, in order to increase the chances of finding a successful treatment, it is important to understand the underlying mechanisms inherent to this type of skeletal muscle injury and the cellular processes involved in muscle healing following a contusion injury. Arguably the most important of these processes is inflammation since it is a consistent and lasting response. The inflammatory response is dependent on two factors, namely the extent of actual physical damage and the degree of muscle vascularization at the time of injury. However, long-term antiinflammatory treatment is not necessarily effective in promoting healing, as indicated by various studies on NSAID treatment. Because of the factors named earlier, human studies on the inflammatory response to contusion injury are limited, but several experimental animal models have been designed to study muscle damage and regeneration. The early recovery phase is characterized by the overlapping processes of inflammation and occurrence of secondary damage. Although neutrophil infiltration has been named as a contributor to the latter, no clear evidence exists to support this claim. Macrophages, although forming part of the inflammatory response, have been shown to have a role in recovery, rather than in exacerbating secondary damage. Several probable roles for this cell type in the second phase of recovery, involving resolution processes, have been identified and include the following: (i) phagocytosis to remove cellular debris; (ii) switching from a pro- to anti-inflammatory phenotype in regenerating muscle; (iii) preventing muscle cells from undergoing apoptosis; (iv) releasing factors to promote muscle precursor cell activation and growth; and (v) secretion of cytokines and growth factors to facilitate vascular and muscle fibre repair. These many different roles suggest that a single treatment with one specific target cell population (e.g. neutrophils. macrophages or satellite cells) may not be equally effective in all phases of the post-injury response. To find the optimal targeted, but time-course-dependent, treatments requires substantial further investigations. However, the techniques currently used to induce mechanical injury vary considerably in terms of invasiveness. tools used to induce injury, muscle group selected for injury and contractile status of the muscle, all of which have an influence on the immune and/or cytokine responses. This makes interpretation of the complex responses more difficult. After our review of the literature, we propose that a standardized non-invasive contusion injury is the ideal model for investigations into the immune responses to mechanical skeletal muscle injury. Despite its suitability as a model, the currently available literature with respect to the inflammatory response to injury using contusion models is largely inadequate. Therefore, it may be premature to investigate highly targeted therapies, which may ultimately prove more effective in decreasing athlete recovery time than current therapies that are either not phase-specific, or not administered in a phase-specific fashion. [ABSTRACT FROM AUTHOR]

Much anecdotal evidence suggests a stress-relieving effect of the Sutherlandia frutescens herb. We investigated this in a model of chronic intermittent immobilization stress in 40 adult male Wistar rats. A warm water extract of Sutherlandia leaves (4 mg/ml) was used as treatment and isotonic saline as placebo, both injected intraperitoneally. The four experimental groups were: a) control + treatment (CS); b) control + placebo (CP); c) immobilization + treatment (IS) and d) immobilization + placebo (IP). After 28 days, resting blood corticosterone, testosterone, interleukin (IL)-6 and tumor necrosis factor (TNF)-α concentrations were measured. Data were analysed with two-way ANOVA. Immobilization stress resulted in significantly increased corticosterone concentrations in IP vs CP (81 ± 11 vs 22 ± 7 ng/ml, P < 0.001), whereas corticosterone concentrations were significantly decreased in IS (43 ± 14 ng/ml, P < 0.05) compared to IR The two Sutherlandia-treated groups did not differ (CS 57 ± 11 ng/ml). Neither testosterone nor IL-6 and TNF-α concentrations were significantly different among groups. In summary, our data show that Sutherlandia frutescens treatment effectively decreased the corticosterone response to chronic stress, thereby scientifically confirming the indigenous wisdom. [ABSTRACT FROM AUTHOR]

Extracellular vesicle (EV) cargo is known to change in response to stimuli such as muscle damage. This study aimed to assess particle size, concentration and microRNA (miR) content within small EV‐enriched separations prepared from human blood taken before and after unaccustomed eccentric‐biased exercise‐induced muscle damage. Nine male volunteers underwent plyometric jumping and downhill running, with blood samples taken at baseline, 2, and 24 h post‐exercise. EVs were separated using size exclusion chromatography (SEC) and their characteristics evaluated by nanoparticle tracking. No changes in EV size or concentration were seen following the muscle‐damaging exercise. Small RNA sequencing identified 240 miRs to be consistently present within the EVs. RT‐qPCR analysis was performed: specifically, for known muscle‐enriched/important miRs, including miR‐1, −206, −133a, −133b, −31, −208b, −451a, −486 and − 499 and the immune‐important miR‐21, −146a and − 155. Notably, none of the immune‐important miRs within the EVs tested changed in response to the muscle damage. Of the muscle‐associated miRs tested, only the levels of miR‐31‐5p were seen to change with decreased levels at 24 h compared to baseline and 2 h, indicating involvement in the damage response. These findings shed light on the dynamic role of EV miRs in response to exercise‐induced muscle damage. [ABSTRACT FROM AUTHOR]

The effects of ankle guards and taping on joint motion before, during, and after exercise were studied. Twelve league squash players played two matches, each last ing 1 hour. Two different ankle guards, and two types of tape applied by the same method, served as sup ports. A specially designed goniometer with electronic digital display (accuracy 1 °) was used to determine joint range of motion: plantar-flexion and dorsiflexion, neutral inversion and eversion, plantar-flexed inversion and eversion. The results were statistically analyzed to de termine the significance of the restriction provided by the supports. This revealed that the two ankle guards provided no significant support. The two tapes, how ever, provided significant support before exercise and after 10 minutes but not after 1 hour of exercise. Nonelastic (zinc oxide) tape proved to be the most restrictive at all times measured, especially prior to exercise, when the ankle's range of motion was de creased between 30% and 50%. However, once exer cise commenced, the tape stretched, and restriction became less effective. [ABSTRACT FROM PUBLISHER]

There is limited scientific justification for the widespread use of vitamin and mineral supplements by athletes. We used a 9-mo, placebo-controlled crossover study design to determine whether a multivitamin and mineral supplement influenced the athletic performance of 30 competitive male athletes. At 0, 3, 6, and 9 mo the runners performed a progressive treadmill test to volitional exhaustion for measurement of maximal oxygen consumption, peak running speed, blood lactate turnpoint, and peak postexercise blood lactate level. Running time in a 15 km time trial was also measured. None of these variables was influenced by 3 mo of active supplementation. We conclude that 3 mo of multivitamin and mineral supplementation was without any measurable ergogenic effect. [ABSTRACT FROM AUTHOR]

The role of subnormal nutrition and sub clinical anorexia nervosa as factors associated with menstrual dysfunction in lean females has not been defined. We studied the relationship between elevated scores for the Eating Attitudes Test (EAT) and the Eating Disorders Inventory (EDI) and menstrual dysfunction in 88 predominantly lean female marathon runners, ballet dancers, and fashion models. For analysis, the subjects were categorized according to their weight classification and exercise status into low-mass non exercisers, low-mass exercisers, and moderate-mass exercisers. Menstrual dysfunction was equally common in all groups (43-55%); the incidence of elevated EAT and EDI scores was high in all groups (15-65%). Elevated EAT test scores, but not body mass or exercise, were associated with menstrual dysfunction (p = 0.009). Subnormal nutrition may be the critical yet unrecognized factor explaining menstrual dysfunction in lean women. [ABSTRACT FROM AUTHOR]

Background. The loss of muscle mass in rheumatoid arthritis (RA), termed rheumatoid cachexia, is predicted to result from the complex interactions between different cell types involved in the maintenance of skeletal muscle mass, namely, myoblasts, fibroblasts, and macrophages. The complexity within the muscle is further highlighted by the incidence of nonresponsiveness to current RA treatment strategies. Method. This study aimed at determining differences in the cellular responses in a novel human primary cell triple coculture model exposed to serum collected from nonarthritic controls (NC), RA treatment naïve (RATN), and RA treatment-nonresponding (RATNR) patients. Bone morphogenetic protein-7 (BMP-7) was investigated as a treatment option. Results. Plasma analysis indicated that samples were indeed representative of healthy and RA patients—notably, the RATNR patients additionally exhibited dysregulated IL-6/IL-10 correlations. Coculture exposure to serum from RATNR patients demonstrated increased cellular growth (p < 0.001), while both hepatocyte growth factor (p < 0.01) and follistatin (p < 0.001) were reduced when compared to NC. Furthermore, decreased concentration of markers of extracellular matrix formation, transforming growth factor-β (TGF-β; p < 0.05) and fibronectin (p < 0.001), but increased collagen IV (p < 0.01) was observed following RATNR serum exposure. Under healthy conditions, BMP-7 exhibited potentially beneficial results in reducing fibrosis-generating TGF-β (p < 0.05) and fibronectin (p < 0.05). BMP-7 further exhibited protective potential in the RA groups through reversing the aberrant tendencies observed especially in the RATNR serum-exposed group. Conclusion. Exposure of the triple coculture to RATN and RATNR serum resulted in dysregulated myoblast proliferation and growth, and ECM impairment, which was reversed by BMP-7 treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor and a response is presented about the article on creatine monohydrate supplementation in rugby athletes.

Rheumatoid arthritis targets numerous organs in patients, including the skeletal muscle, resulting in rheumatoid cachexia. In the muscle niche, satellite cells, macrophages, and myofibroblasts may be affected and the factors they release altered. This study aimed to assess these cell types, cytokines, and growth factors and their relationships to muscle fiber size and number in a rodent collagen‐induced arthritis (CIA) model, in order to identify new therapeutic targets. Fiber cross‐sectional area (CSA) was 57% lower in CIA than controls (p < 0.0001), thus smaller but more fibers visible per field of view. Immunostaining indicated the increased presence of satellite cells, macrophages, myofibroblasts, and myonuclei per field of view in CIA (p < 0.01), but this finding was not maintained when taking fiber number into consideration. Western blots of gastrocnemius samples indicated that tumor necrosis factor‐α was significantly elevated (p < 0.01) while interleukin‐10 (IL‐10) was decreased (p < 0.05) in CIA. This effect was maintained (and heightened for IL‐10) when expressed per fiber number. Myogenic regulatory factors (MyoD and myogenin), transforming growth factor‐β and inhibitor of differentiation were significantly elevated in CIA muscle and levels correlated significantly with CSA. Several of these factors remained elevated, but bone morphogenetic protein‐7 decreased when considering fiber number per area. In conclusion, CIA‐muscle demonstrated a good regenerative response. Myoblast numbers per fiber were not elevated, suggesting their activity results from the persistent inflammatory signaling which also significantly hampered maintenance of muscle fiber size. A clearer picture of signaling events at cellular level in arthritis muscle may be derived from expressing data per fiber. [ABSTRACT FROM AUTHOR]

Satellite cells are generally quiescent in vivo. Once activated, progression through the cell cycle begins. Immortalised myoblasts from a single cell line are fairly homogenous in culture, but primary human myoblasts (PHMs) demonstrate heterogeneity. This phenomenon is poorly understood however may impact on PHM expansion. This study aimed to evaluate cell cycle transition from growth to synthesis phases of the cell cycle (G1 to S phase) and total mRNA relevant to this transition in PHM clones derived from 2 donor biopsies. Proportions of cells transitioning from G1 to S phase were evaluated at 2-hourly intervals for 24 h (n = 3 for each) and total mRNA quantified. Both PHM clones revealed an exponential transition from G1 to S phase over time, with a significantly slower rate for PHMs from S9.1 compared to S6.3, which had a higher proportion of PHMs in S phase for most time-points (p < 0.05). After 24 h the proportion of PHMs in S phase was ∼13% (S6.3) compared to ∼22% (S9.1). Gene transcription increased as cells progressed from G1 to S phase. Although total RNA increased with similar linearity in both clones, S6.3 PHMs had consistently (10 out of 12 time points) significantly higher concentrations. Validating the 2-hourly assessment over 24 h, a 4-hourly assessment from 8 to 32 h revealed similar differences but included the beginning of a plateau. This study demonstrates that PHMs from different donors differ in both cell cycle progression and overall transcriptome revealing new aspects in the heterogeneity of isolated satellite cells in vitro. • Primary cell expansion requires standardised proliferation dynamics assessment. • PHM clones differed in area, perimeter, RNA concentration and cell cycle phases. • Proportion of cells in S-phase increased exponentially from 0 to 24 h after plating. • The PHM clone with more cells in S-phase corresponded with higher RNA concentration. • The PHM clones did not equalise over time but % in S-phase plateaued after 28 h. [ABSTRACT FROM AUTHOR]

Chronic wounds are a serious and debilitating complication of diabetes. A better understanding of the dysregulated healing responses following injury will provide insight into the optimal time frame for therapeutic intervention. In this study, a direct comparison was done between the healing dynamics and the proteome of acute and obese diabetic wounds on days 2 and 7 following injury. Full thickness excisional wounds were induced on obese diabetic (B6.Cg-lepob/J, ob/ob, n = 14) (blood glucose 423.25 ± 127.92 mg/dL) and WT control (C57BL/6J, n = 14) (blood glucose 186.67 ± 24.5 mg/dL) mice. Histological analysis showed no signs of healing in obese DM wounds whereas complete wound closure/re-epithelisation, the formation of granulation tissue and signs of re-vascularisation, was evident in acute wounds on day 7. In obese DM wounds, substance P deficiency and increased MMP-9 activity on day 2 coi ncided with increased cytokine/chemokine levels within wound fluid. LC-MS/MS identified 906 proteins, of which 23 (Actn3, Itga6, Epb41, Sncg, Nefm, Rsp18, Rsp19, Rpl22, Macroh2a1, Rpn1, Ppib, Snrnp70, Ddx5, Eif3g, Tpt1, FABP5, Cavin1, Stfa1, Stfa3, Cycs, Tkt, Mb, Chmp2a) were differentially expressed in wounded tissue on day 2 (P < 0.05; more than two-fold) and 6 (Cfd, Ptms, Hp, Hmga1, Cbx3, Syap1) (P < 0.05; more than two-fold) on day 7. A large number of dysregulated proteins on day 2 was associated with an inability to progress into the proliferative stage of healing and suggest that early intervention might be pivotal for effective healing outcomes. The proteomic approach highlighted the complexity of obese DM wounds in which the dysregulation involves multiple regulatory pathways and biological processes. [ABSTRACT FROM AUTHOR]

Women have a disadvantage for performance in long-distance running compared with men. To elaborate on inherent characteristics, 12 subelite women were matched with 12 men for training volume (M-Tm) (56.6 ± 18 vs. 55.7 ± 17 km/wk). The women were also matched to other men for a 10 km staged outdoor time trial (M-Pm) (42:36 min:s) to determine which factors could explain equal running performance. Anthropometry and treadmill tests were done. Fiber type (% Type I and Type IIA) and citrate synthase activities were analyzed in muscle biopsy samples. Consistent sex differences for both comparisons included height, weight, % body fat ( P < 0.01), and hematocrit ( P < 0.05). Women had lower V̇o 2max and peak treadmill speed (PTS) compared with both M-Tm and M-Pm ( P < 0.01). Training matched pairs had no sex difference in % PTS at race pace but compared with M-Pm women ran at a higher % PTS ( P < 0.05) and %HR max ( P < 0.01) at race pace. On average, the women trained 22.9 km/wk more than M-Pm (+67.5%, P < 0.01). This training was not associated with higher V̇o 2max or better running economy. Muscle morphology and oxidative capacity did not differ between groups. Percentage body fat remained significantly higher in women. In conclusion, women matched to men for training volume had slower 10 km performance (-10.5% P < 0.05). Higher training volume, more high-intensity sessions/wk, and time spent training in the 95%-100% HR max zone may explain the higher % PTS and %HR max at race pace in women compared with performance-matched men. NEW & NOTEWORTHY When subelite women 10 km runners were matched with male counterparts for 10 km race performance, inherent differences in % body fat, V̇o 2max , Hct, and peak treadmill speed were counteracted by significantly higher training volume, more time training at higher %HRmax and consequently, higher %HRmax and %PTS at race pace. Citrate synthase activity and muscle fiber types did not differ. When women and men matched for training, 10 km performance of men was 10.5% faster.

Background: Maternal malaria may restrict foetal growth. Impaired utero-placental blood flow due to malaria infection may cause hypoxia-induced altered skeletal muscle fibre type distribution in the offspring, which may contribute to insulin resistance and impaired glucose metabolism. This study assessed muscle fibre distribution 20 years after placental and/or peripheral in-utero malaria exposure compared to no exposure, i.e., PPM+, PM+, and M-, respectively., Methods: We traced 101 men and women offspring of mothers who participated in a malaria chemosuppression study in Muheza, Tanzania. Of 76 eligible participants, 50 individuals (29 men and 21 women) had skeletal muscle biopsy taken from m . vastus lateralis in the right leg. As previously reported, fasting and 30 min post-oral glucose challenge plasma glucose values were higher, and insulin secretion disposition index was lower, in the PPM+ group. Aerobic capacity (fitness) was estimated by an indirect VO 2 max test on a stationary bicycle. Muscle fibre sub-type (myosin heavy chain, MHC) distribution was analysed, as were muscle enzyme activities (citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, myophosphorylase, phosphofructokinase, lactate dehydrogenase, and creatine kinase activities. Between-group analyses were adjusted for MHC-I %., Results: No differences in aerobic capacity were found between groups. Despite subtle elevations of plasma glucose levels in the PPM+ group, there was no difference in MHC sub-types or muscle enzymatic activities between the malaria-exposed and non-exposed groups., Conclusion: The current study did not show differences in MHC towards glycolytic sub-types or enzymatic activity across the sub-groups. The results support the notion of the mild elevations of plasma glucose levels in people exposed to placental malaria in pregnancy being due to compromised pancreatic insulin secretion rather than insulin resistance., Competing Interests: DC has received payment from Novo Nordisk Mexico for consultancy work. AV is a shareholder in Astra Zeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Christensen, Mutabingwa, Bygbjerg, Vaag, Grunnet, Lajeunesse-Trempe, Nielsen, Schmiegelow, Ramaiya and Myburgh.)

Recognition of diseases associated with mutations of the chaperone system genes, e.g., chaperonopathies, is on the rise. Hereditary and clinical aspects are established, but the impact of the mutation on the chaperone molecule and the mechanisms underpinning the tissue abnormalities are not. Here, histological features of skeletal muscle from a patient with a severe, early onset, distal motor neuropathy, carrying a mutation on the CCT5 subunit (MUT) were examined in comparison with normal muscle (CTR). The MUT muscle was considerably modified; atrophy of fibers and disruption of the tissue architecture were prominent, with many fibers in apoptosis. CCT5 was diversely present in the sarcolemma, cytoplasm, and nuclei in MUT and in CTR and was also in the extracellular space; it colocalized with CCT1. In MUT, the signal of myosin appeared slightly increased, and actin slightly decreased as compared with CTR. Desmin was considerably delocalized in MUT, appearing with abnormal patterns and in precipitates. Alpha-B-crystallin and Hsp90 occurred at lower signals in MUT than in CTR muscle, appearing also in precipitates with desmin. The abnormal features in MUT may be the consequence of inactivity, malnutrition, denervation, and failure of protein homeostasis. The latter could be at least in part caused by malfunction of the CCT complex with the mutant CCT5 subunit. This is suggested by the results of the in silico analyses of the mutant CCT5 molecule, which revealed various abnormalities when compared with the wild-type counterpart, mostly affecting the apical domain and potentially impairing chaperoning functions. Thus, analysis of mutated CCT5 in vitro and in vivo is anticipated to provide additional insights on subunit involvement in neuromuscular disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scalia, Barone, Rappa, Marino Gammazza, Lo Celso, Lo Bosco, Barone, Antona, Vadalà, Vitale, Donato Mangano, Amato, Sentiero, Macaluso, Myburgh, Conway de Macario, Macario, Giuffrè and Cappello.)

This perspective aims to highlight the lack of current knowledge on sarcopenic obesity in Africa and to call for diagnostic methods and appropriate interventions. Sarcopenic obesity has been defined as obesity that occurs in combination with low muscle mass and function, which is typically evident in older adults. However, there has been no clear consensus on population-specific diagnostic criterion, which includes both gold-standard measures that can be used in a more advanced health care system, and surrogate measures that can be used in low-income settings with limited resources and funding. Importantly, low and middle-income countries (LMICs) across Africa are in an ongoing state of economic and social transition, which has contributed to an increase in the aging population, alongside the added burden of poverty, obesity, and associated co-morbidities. It is anticipated that alongside the increased prevalence of obesity, these countries will further experience an increase in age-related musculoskeletal diseases such as sarcopenia. The developmental origins of health and disease (DOHaD) approach will allow clinicians and researchers to consider developmental trajectories, and the influence of the environment, for targeting high-risk individuals and communities for treatment and/or prevention-based interventions that are implemented throughout all stages of the life course. Once a valid and reliable diagnostic criterion is developed, we can firstly assess the prevalence and burden of sarcopenic obesity in LMICs in Africa, and secondly, develop appropriate and sustainable interventions that target improved dietary and physical activity behaviors throughout the life course., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mendham, Lundin-Olsson, Goedecke, Micklesfield, Christensen, Gallagher, Myburgh, Odunitan-Wayas, Lambert, Kalula, Hunter and Brooks.)

Background: High rates of food insecurity, obesity and obesity-related comorbidities in ageing South African (SA) women may amplify the risk of developing sarcopenic obesity. This study aimed to investigate the prevalence and correlates of sarcopenic obesity and its diagnostic components [grip strength, appendicular skeletal muscle mass (ASM) and body mass index (BMI)] in older SA women from a low-income setting., Methods: This cross-sectional study recruited black SA women between the ages of 60-85 years (n = 122) from a low-income community. Testing included a fasting blood sample (markers of cardiometabolic risk, HIV), whole body and regional muscle and fat mass (dual-energy absorptiometry x-ray), anthropometry, blood pressure, functional movement tests, current medication use, demographic and health questionnaires, physical activity (PA; accelerometery), household food insecurity access scale, and a one-week quantified food frequency questionnaire. Foundation for the National Institutes of Health (FNIH) criteria (grip strength and ASM, adjusted for BMI) were used to classify sarcopenia. Participants with sarcopenia alongside a BMI of > 30.0 kg/m 2 were classified as having sarcopenic obesity. Prevalence using other criteria (European Working Group on Sarcopenia in Older People, Asian Working Group for Sarcopenia and the International Working Group for Sarcopenia) were also explored., Results: The prevalence of sarcopenia was 27.9%, which comprised of sarcopenia without obesity (3.3%) and sarcopenic obesity (24.6%). Other classification criteria showed that sarcopenia ranged from 0.8-14.7%, including 0.8-9.8% without obesity and 0-4.9% with sarcopenic obesity. Using multivariate-discriminant analysis (OPLS-DA) those with sarcopenic obesity presented with a descriptive profile of higher C-reactive protein, waist circumference, food security and sedentary time than women without sarcopenic obesity (p = 0.046). A similar profile described women with low BMI-adjusted grip strength (p < 0.001)., Conclusions: The majority of women with sarcopenia were also obese (88%). We show a large discrepancy in the diagnostic criteria and the potential for significantly underestimating the prevalence of sarcopenia if BMI is not adjusted for. The main variables common to women with sarcopenic obesity were higher food security, lower PA and chronic inflammation. Our data highlights the importance of addressing obesity within these low-income communities to ensure the prevention of sarcopenic obesity and that quality of life is maintained with ageing.

Skeletal muscle regeneration is a complex process influenced by non-myogenic macrophages and fibroblasts, which acquire different phenotypes in response to changes in the injury milieu or changes in experimental conditions. In vitro, serum stimulates the differentiation of fibroblasts into myofibroblasts, while lipopolysaccharide (LPS) stimulates the polarization of unstimulated (M0) macrophages to acquire an M1 pro-inflammatory phenotype. We characterized these phenotypes using morphology (with circularity as shape descriptor; perfect circularity = 1.0) and phenotype-specific markers. Myofibroblasts (high α-smooth muscle actin [SMA] expression) had high circularity (mean 0.60 ± 0.03). Their de-differentiation to fibroblasts (low α-SMA expression) significantly lessened circularity (0.47 ± 0.01 and 0.35 ± 0.02 in 2% or 0% serum culture media respectively (p < 0.05). Unstimulated (M0) macrophages (no CD86 expression) had high circularity (0.72 ± 0.02) which decreased when stimulated to M1 macrophages (CD86 expression) (LPS; 0.61 ± 0.02; p < 0.05). Utilizing these established conditions, we then co-cultured M1 macrophages with myofibroblasts or myoblasts. M1 macrophages significantly decreased relative myofibroblast numbers (from 223 ± 22% to 64 ± 7%), but not myoblast numbers. This pro-inflammatory co-culture model was used to rapidly screen the following four compounds for ability to prevent M1 macrophage-mediated decrease in myofibroblast numbers: L-NAME (inducible nitric oxide synthase inhibitor), SB203580 (p38 mitogen-activated protein kinase inhibitor), SP600125 (c-Jun N-terminal kinase inhibitor) and LY294002 (phosphoinositide 3-kinase [PI3K] inhibitor). We found that LY294002 rescued myofibroblasts and decreased macrophage numbers. Myofibroblast rescue did not occur with L-NAME, SB203580 or SP600125 incubation. In conclusion, these data suggest a PI3K-associated mechanism whereby myofibroblasts can be rescued, despite simulated pro-inflammatory conditions., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Adult skeletal muscle stem cells, satellite cells, remain in an inactive or quiescent state in vivo under physiological conditions. Progression through the cell cycle, including activation of quiescent cells, is a tightly regulated process. Studies employing in vitro culture of satellite cells, primary human myoblasts (PHMs), necessitate isolation myoblasts from muscle biopsies. Further studies utilizing these cells should endeavour to represent their native in vivo characteristics as closely as possible, also considering variability between individual donors. This study demonstrates the approach of utilizing KnockOut™ Serum Replacement (KOSR)-supplemented culture media as a quiescence-induction media for 10 days in PHMs isolated and expanded from three different donors. Cell cycle analysis demonstrated that treatment resulted in an increase in G 1 phase and decreased S phase proportions in all donors (p < 0.005). The proportions of cells in G 1 and G 2 phases differed in proliferating myoblasts when comparing donors (p < 0.05 to p < 0.005), but following KOSR treatment, the proportion of cells in G 1 (p = 0.558), S (p = 0.606) and G 2 phases (p = 0.884) were equivalent between donors. When cultured in the quiescence-induction media, expression of CD34 and Myf5 remained constant above > 98% over time from day 0 to day 10. In contrast activation (CD56), proliferation (Ki67) and myogenic marker MyoD decreased, indicated de-differentiation. Induction of quiescence was accompanied in all three clones by fold change in p21 mRNA greater than 3.5 and up to tenfold. After induction of quiescence, differentiation into myotubes was not affected. In conclusion, we describe a method to induce quiescence in PHMs from different donors.

Supplement use among athletes is widespread, including non-traditional and biological compounds. Despite increasing research, a comprehensive and critical review on polyphenol supplementation and exercise is still lacking. This review is relevant for researchers directly involved in the topic, as well as those with a broad interest in athletic performance enhancement and sports nutrition. The purpose of this review is to present background information on groups of polyphenols and their derivatives because their differing chemical structures influence mechanisms of action; to discuss the potential of plant, fruit and vegetable-based biological supplements, high in polyphenol content, to affect exercise performance and biomarkers of oxidative stress and exercise-induced muscle damage; and to critically discuss the exercise studies and biomarkers used. Subjects in the studies reviewed were either sedentary, healthy individuals, or active, recreationally trained or well-trained athletes. Polyphenol supplementation in exercise studies included mainly extracts (multicomponent or purified), juices, infusions or an increased intake of polyphenol-rich foods. This review includes details of supplement doses and exercise test protocols. Many studies considered only the performance or one or two selected biomarkers of antioxidant capacity instead of a comprehensive choice of biomarkers to assess damage to lipids or proteins. Evidence is insufficient to make recommendations for or against the use of polyphenol supplementation (neither specific polyphenols nor specific doses) for either recreational, competitive or elite athletes. Polyphenols have multiple biological effects, and future exercise studies must be designed appropriately and specifically to determine physiological interactions between exercise and the selected supplement, rather than considering performance alone.

Skeletal muscle protein loss, known as atrophy, occurs during inactivity, disease, and aging. Atrophy may be the result of increased catabolic factors, e.g. glucocorticoids, or reduced influence of anabolic factors, e.g. insulin. The purpose of this study was to investigate atrophy, signaling mechanisms, and apoptosis in a rat model of restraint stress in 40 adult male Wistar rats. Due to the anxiolytic effects of Sutherlandia frutescens, we also determined if any of the molecular events in gastrocnemius muscle would be affected by daily treatment with S. frutescens. Rats were randomly assigned to four experimental groups: control placebo (CP); control Sutherlandia (CS) treatment; Restraint Placebo (RP) and Restraint Sutherlandia (RS) treatment. Restraint resulted in a significant increase in myostatin which was significantly reduced with Sutherlandia treatment. In addition, MyoD expression was significantly attenuated in RP and this effect was also counteracted by Sutherlandia treatment. Restraint also resulted in a significant attenuation of the PI3-Kinase/Akt signaling pathway and increased apoptosis which was reversed with Sutherlandia treatment. This study demonstrates for the first time that psychological stress elevates markers of muscle atrophy and apoptosis, whilst a herbal remedy, Sutherlandia, inhibits apoptosis, and signaling pathways associated with muscle atrophy.