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Sample records for human aging muscle

  1. Molecular aging and rejuvenation of human muscle stem cells

    DEFF Research Database (Denmark)

    Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

    2009-01-01

    Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans....... Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular...

  2. THE CAPILLARY PATTERN IN HUMAN MASSETER MUSCLE DURING AGEING

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    Erika Cvetko

    2013-10-01

    Full Text Available The effect of ageing on the capillary network in skeletal muscles has produced conflicting results in both, human and animals studies. Some of the inconsistencies are due to non-comparable and biased methods that were applied on thin transversal sections, especially in muscles with complicated morphological structures, such as in human masseter muscle. We present a new immunohistochemical method for staining capillaries and muscle fibres in 100 µm thick sections as well as novel approach to 3D visualization of capillaries and muscle fibres. Applying confocal microscopy and virtual 3D stereological grids, or tracing capillaries in virtual reality, length of capillaries within a muscle volume or length of capillaries adjacent to muscle fibre per fibre length, fibre surface or fibre volume were evaluated in masseter muscle of young and old subjects by an unbiased approach. Our findings show that anatomic capillarity is well maintained in masseter muscle in old subjects; however, vascular remodelling occurs with age, which could be a response to changed muscle function and age-related muscle fibre type transformations.

  3. Relationship between Human Aging Muscle and Oxidative System Pathway

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    Enrico Doria

    2012-01-01

    Full Text Available Ageing is a complex process that in muscle is usually associated with a decrease in mass, strength, and velocity of contraction. One of the most striking effects of ageing on muscle is known as sarcopenia. This inevitable biological process is characterized by a general decline in the physiological and biochemical functions of the major systems. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS generated by the addition of a single electron to the oxygen molecule. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fibre composition, muscle type, and function.

  4. Molecular networks of human muscle adaptation to exercise and age.

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    Bethan E Phillips

    2013-03-01

    Full Text Available Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44 who then undertook 20 weeks of supervised resistance-exercise training (RET. Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%, and when applying Ingenuity Pathway Analysis (IPA up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR signaling associating with growth (P = 1.4 × 10(-30. Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6 × 10(-13 and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = -2.3; P = 3 × 10(-7 with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET, they appear to represent "generic" physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52, with a continuum of subject ages (18-78 y, the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1 × 10(-6 and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to

  5. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

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    Suetta, Charlotte; Frandsen, Ulrik; Nielsen, Line;

    2012-01-01

    Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1a and PGC-1ß (1-4 days) and a ~10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

  6. Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

    OpenAIRE

    Pietrangelo, Tiziana; Puglielli, Cristina; Mancinelli, Rosa; Beccafico, Sara; Fanò, Giorgio; Fulle, Stefania

    2009-01-01

    Abstract Sarcopenia is the age-related loss of muscle mass, strength and function. Human muscle proteins are synthesized at a slower rate in the elderly than in young adults, leading to atrophy and muscle mass loss with a decline in the functional capability. Additionally, aging is accompanied by a decrease in the ability of muscle tissue to regenerate following injury or overuse due to the impairment of intervening satellite cells, in which we previously reported oxidative damage ...

  7. Reduced blood flow to contracting skeletal muscle in ageing humans

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    Nyberg, Michael Permin; Hellsten, Ylva

    2016-01-01

    consequences of ageing and physical inactivity can be challenging; yet, observations from cross-sectional and longitudinal studies on the effects of physical activity have provided some insight. Physical activity has the potential to offset the age-related decline in blood flow to contracting skeletal muscle...... and the ability for functional sympatholysis; an attenuation of the vasoconstrictor effect of sympathetic nervous activity. These vascular adaptations with physical activity are likely to be an effect of improved nitric oxide and ATP signaling. Collectively, precise matching of blood flow and O2 delivery to meet...

  8. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy.

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    Charlotte Suetta

    Full Text Available Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2-4 days of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days and a ~10% decrease in myofiber size (4 days. Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days of immobilization. In contrast, Akt phosphorylation was unchanged in old muscle after 2 days and increased after 4 days of immobilization. Further, an age-specific down-regulation of MuRF-1 and Atrogin-1 expression levels was observed following 2 weeks of immobilization, along with a slowing atrophy response in aged skeletal muscle. Neither the immediate loss of muscle mass, nor the subsequent age-differentiated signaling responses could be explained by changes in inflammatory mediators, apoptosis markers or autophagy indicators. Collectively, these findings indicate that the time-course and regulation of human skeletal muscle atrophy is age dependent, leading to an attenuated loss in aging skeletal muscle when exposed to longer periods of immobility-induced disuse.

  9. Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle

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    Hütter, Eveline; Skovbro, Mette; Lener, Barbara;

    2007-01-01

    According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain....... However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated...... from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high-resolution respirometry, and ROS production was analyzed by in situ staining with the redox-sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional...

  10. Protein carbonylation and heat shock proteins in human skeletal muscle: relationships to age and sarcopenia.

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    Beltran Valls, Maria R; Wilkinson, Daniel J; Narici, Marco V; Smith, Kenneth; Phillips, Bethan E; Caporossi, Daniela; Atherton, Philip J

    2015-02-01

    Aging is associated with a gradual loss of muscle mass termed sarcopenia, which has significant impact on quality-of-life. Because oxidative stress is proposed to negatively impact upon musculoskeletal aging, we investigated links between human aging and markers of oxidative stress, and relationships to muscle mass and strength in young and old nonsarcopenic and sarcopenic adults. Sixteen young and 16 old males (further subdivided into "old" and "old sarcopenic") were studied. The abundance of protein carbonyl adducts within skeletal muscle sarcoplasmic, myofibrillar, and mitochondrial protein subfractions from musculus vastus lateralis biopsies were determined using Oxyblot immunoblotting techniques. In addition, concentrations of recognized cytoprotective proteins (eg, heat shock proteins [HSP], αβ-crystallin) were also assayed. Aging was associated with increased mitochondrial (but not myofibrillar or sarcoplasmic) protein carbonyl adducts, independently of (stage-I) sarcopenia. Correlation analyses of all subjects revealed that mitochondrial protein carbonyl abundance negatively correlated with muscle strength ([1-repetition maximum], p = .02, r (2) = -.16), but not muscle mass (p = .13, r (2) = -.08). Abundance of cytoprotective proteins, including various HSPs (HSP 27 and 70), were unaffected by aging/sarcopenia. To conclude, these data reveal that mitochondrial protein carbonylation increases moderately with age, and that this increase may impact upon skeletal muscle function, but is not a hallmark of (stage-I) sarcopenia, per se. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.

  11. IMPROVING METHODOLOGICAL STRATEGIES FOR SATELLITE CELLS COUNTING IN HUMAN MUSCLE DURING AGEING

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    Špela Sajko

    2011-05-01

    Full Text Available Stereological methods, based on the optical disector principle and fluorescent staining, were developed for estimating frequency of satellite cells in skeletal muscles. The parameter NL(sc, fib (number of satellite cells per fibre length was compared with the parameter NN(sc, nucl (the percentage of satellite cell nuclei in all muscle nuclei, most often published in the literature, by applying unbiased sampling and counting procedures and using a confocal microscope. The methods were tested in autopsy samples of four young vs. four old human vastus lateralis muscles. Both parameters NL(sc, fib and NN(sc, nucl declined during ageing. However, it appears that the two parameters cannot be substituted one by the other because the number of nuclei per fibre length tends to be increased during aging. Using the introduced methods, it is more straightforward to estimate NL(sc, fib than NN(sc, nucl.

  12. Experimental evidence against the mitochondrial theory of aging - A study of isolated human skeletal muscle mitochondria

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    Rasmussen, Ulla Fugmann; Krustrup, Peter; Kjær, Michael;

    2003-01-01

    age effects, ATP formation, BSA effects, collagen content, low temperature spectroscopy, oxygen uptakes, quadriceps muscle, respiration, specific enzyme activities......age effects, ATP formation, BSA effects, collagen content, low temperature spectroscopy, oxygen uptakes, quadriceps muscle, respiration, specific enzyme activities...

  13. Experimental evidence against the mitochondrial theory of aging - A study of isolated human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

    Rasmussen, Ulla Fugmann; Krustrup, Peter; Kjær, Michael

    2003-01-01

    age effects, ATP formation, BSA effects, collagen content, low temperature spectroscopy, oxygen uptakes, quadriceps muscle, respiration, specific enzyme activities......age effects, ATP formation, BSA effects, collagen content, low temperature spectroscopy, oxygen uptakes, quadriceps muscle, respiration, specific enzyme activities...

  14. Reconditioning aging muscles.

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    Kraus, H

    1978-06-01

    Weakness or stiffness of key posture muscles can cause much of the disability seen in elderly patients. Too much tension and too little exercise greatly increase the natural loss of muscular fitness with age. A systematic program of exercise, stressing relaxation and stretching of tight muscles and strenghthening of weak muscles, can improve physical fitness. The program must be tailored to the patient, starting with relaxation and gentle limbering exercises and proceeding ultimately to vigorous muscle-stretching exercises. Muscle aches and pain from tension and muscle imbalance are to be expected. Relaxation relieves tension pain, and strengthening weak muscles and stretching tight muscles will correct muscle imbalance. To prevent acute muscle spasm, the patient should avoid excessive exertion and increase exercise intensity gradually.

  15. Investigation of age-related changes in LMNA splicing and expression of progerin in human skeletal muscles.

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    Luo, Yue-Bei; Mitrpant, Chalermchai; Johnsen, Russell D; Fabian, Victoria A; Fletcher, Sue; Mastaglia, Frank L; Wilton, Steve D

    2013-01-01

    Age-related changes in splice-forms of LMNA, which encodes the nuclear lamina proteins lamin A/C, have not been investigated in skeletal muscle. In the rare premature ageing disease, Hutchinson-Gilford progeria syndrome (HGPS), de novo point mutations in LMNA activate a cryptic splice site in exon 11, resulting in a 150 base deletion in LMNA mRNA and accumulation of a truncated protein isoform, progerin. The LMNA Δ150 progerin transcript has also been found in trace quantities in tissues of healthy people and its implication in 'natural' ageing has been proposed. We therefore investigated the expression of progerin and lamin A/C in normal human and mouse skeletal muscles of different ages. LMNA Δ150 was detected in most muscle samples from healthy individuals aged 16-71 years, but was not present in any mouse muscle samples up to the age of 18 months. Real time qPCR of human muscle samples showed that there was an age-related increase in both the full length lamin A and LMNA Δ150 transcripts, whereas their protein levels did not change significantly with age. These findings indicate that there is a basal level of mis-splicing during LMNA expression that does not change with ageing in human muscle, but at levels that do not result in increased aberrant protein. The significance of these findings in the pathophysiology of muscle ageing is uncertain and warrants further investigation.

  16. Type ⅡB human skeletal muscle fibers positively correlate with bone mineral density irrespective to age

    Institute of Scientific and Technical Information of China (English)

    Wing-Hoi Cheung; Wing-Sze Lee; Ling Qin; Ning Tang; Vivian Wing-Yin Hung; Kwok-Sui Leung

    2010-01-01

    Background Age-associated decrease in type ⅡA/B human skeletal muscle fibers was detected in human biopsies in our previous study. The relationship between change in muscle fiber typing and bone mineral density (BMD) is, however,unknown either cross-sectionally or longitudinally. We therefore conducted a cross-sectional study to investigate their correlation using human muscle biopsies.Methods Forty human subjects aged (53.4±20.2) years were recruited. Histomorphometric parameters of their muscle biopsies were measured by ATPase staining and image analysis, including average area percentage, fiber number percentage, mean fiber area, and area percentage of connective tissues. Hip and spine BMD was measured by dual-energy X-ray absorptiometry. Partial correlation with adjusting age was performed.Results Type ⅡB muscle fiber was found positively correlated with hip BMD irrespective to age and demonstrated significantly stronger relationship with BMD among all fiber types, in terms of its cross-sectional area (r=0.380, P=0.029)and size (r=0.389, P=0.025). Type ⅡA muscle fibers associated with hip BMD in mean fiber area only (r=0.420, P=0.015).Conclusions Type ⅡB muscle fiber may play an important role in maintaining bone quality. This may also be a relatively more sensitive fiber type of sarcopenia and osteoporosis. These findings further consolidate the muscle-bone relationship.

  17. Effects of aging on human skeletal muscle after immobilization and retraining

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    Suetta, C; Hvid, L G; Justesen, L

    2009-01-01

    Inactivity is a recognized compounding factor in sarcopenia and muscle weakness in old age. However, while the negative effects of unloading on skeletal muscle in young individuals are well elucidated, only little is known about the consequence of immobilization and the regenerative capacity...... in elderly individuals. Thus the aim of this study was to examine the effect of aging on changes in muscle contractile properties, specific force, and muscle mass characteristics in 9 old (61-74 yr) and 11 young men (21-27 yr) after 2 wk of immobilization and 4 wk of retraining. Both young and old...

  18. Role of microRNAs in the age-related changes in skeletal muscle and diet or exercise interventions to promote healthy aging in humans.

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    McGregor, Robin A; Poppitt, Sally D; Cameron-Smith, David

    2014-09-01

    Progressive age-related changes in skeletal muscle mass and composition, underpin decreases in muscle function, which can inturn lead to impaired mobility and quality of life in older adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in skeletal muscle and are associated with aging. Accumulating evidence suggests that miRNAs play an important role in the age-related changes in skeletal muscle mass, composition and function. At the cellular level, miRNAs have been demonstrated to regulate muscle cell proliferation and differentiation. Furthermore, miRNAs are involved in the transitioning of muscle stem cells from a quiescent, to either an activated or senescence state. Evidence from animal and human studies has shown miRNAs are modulated in muscle atrophy and hypertrophy. In addition, miRNAs have been implicated in changes in muscle fiber composition, fat infiltration and insulin resistance. Both exercise and dietary interventions can combat age-related changes in muscle mass, composition and function, which may be mediated by miRNA modulation in skeletal muscle. Circulating miRNA species derived from myogenic cell populations represent potential biomarkers of aging muscle and the molecular responses to exercise or diet interventions, but larger validation studies are required. In future therapeutic approaches targeting miRNAs, either through exercise, diet or drugs may be able to slow down or prevent the age-related changes in skeletal muscle mass, composition, function, hence help maintain mobility and quality of life in old age.

  19. Age- and Activity-Related Differences in the Abundance of Myosin Essential and Regulatory Light Chains in Human Muscle

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    James N. Cobley

    2016-04-01

    Full Text Available Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM. We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping.

  20. Morphometric analysis of somatotropic cells of the adenohypophysis and muscle fibers of the psoas muscle in the process of aging in humans.

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    Antić, Vladimir M; Stefanović, Natalija; Jovanović, Ivan; Antić, Milorad; Milić, Miroslav; Krstić, Miljan; Kundalić, Braca; Milošević, Verica

    2015-07-01

    The aim of this research was to quantify changes of the adenohypophyseal somatotropes and types 1 and 2 muscle fibers with aging, as well as to establish mutual interactions and correlations with age. Material was samples of hypophysis and psoas major muscle of 27 cadavers of both genders, aged from 30 to 90 years. Adenohypophyseal and psoas major tissue sections were immunohistochemically processed and stained by anti-human growth hormone and anti-fast myosin antibodies, respectively. Morphometric analysis was performed by ImageJ. Results of morphometric analysis showed a significant increase in the somatotrope area, and significant decrease in somatotrope volume density and nucleocytoplasmic ratio with age. Cross-sectional areas of types 1 and 2, and volume density of type 2 muscle fibers decreased significantly with age. One Way ANOVA showed that the latter cited changes in the somatotropes and types 1 and 2 muscle fibers mostly become significant after the age of 70. Significant positive correlation was observed between the area of the somatotropes and volume density of type 2 muscle fibers. A significant negative correlation was detected between the nucleocytoplasmic ratio of the somatotropes and cross-sectional areas of types 1 and 2 muscle fibers. So, it can be concluded that after the age of 70, there is significant loss of the anterior pituitary's somatotropes associated with hypertrophy and possible functional decline of the remained cells. Age-related changes in the somatotropes are correlated with the simultaneous atrophy of type 1, as well as with the atrophy and loss of type 2 muscle fibers.

  1. Skeletal muscle myofilament adaptations to aging, disease and disuse and their effects on whole muscle performance in older adult humans

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    Mark Stuart Miller

    2014-09-01

    Full Text Available Skeletal muscle contractile function declines with aging, disease and disuse. In vivo muscle contractile function depends on a variety of factors, but force, contractile velocity and power generating capacity ultimately derive from the summed contribution of single muscle fibers. The contractile performance of these fibers are, in turn, dependent upon the isoform and function of myofilament proteins they express, with myosin protein expression and its mechanical and kinetic characteristics playing a predominant role. Alterations in myofilament protein biology, therefore, may contribute to the development of functional limitations and disability in these conditions. Recent studies suggest that these conditions are associated with altered single fiber performance due to decreased expression of myofilament proteins and/or changes in myosin-actin cross-bridge interactions. Furthermore, cellular and myofilament-level adaptations are related to diminished whole muscle and whole body performance. Notably, the effect of these various conditions on myofilament and single fiber function tends to be larger in older women compared to older men, which may partially contribute to their higher rates of disability. To maintain functionality and provide the most appropriate and effective countermeasures to aging, disease and disuse in both sexes, a more thorough understanding is needed of the contribution of myofilament adaptations to functional disability in older men and women and their contribution to tissue level function and mobility impairment.

  2. Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

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    Zampieri, Sandra; Mammucari, Cristina; Romanello, Vanina; Barberi, Laura; Pietrangelo, Laura; Fusella, Aurora; Mosole, Simone; Gherardi, Gaia; Höfer, Christian; Löfler, Stefan; Sarabon, Nejc; Cvecka, Jan; Krenn, Matthias; Carraro, Ugo; Kern, Helmut; Protasi, Feliciano; Musarò, Antonio; Sandri, Marco; Rizzuto, Rosario

    2016-12-01

    Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca(2+) homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca(2+) uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca(2+) homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  3. Heterogeneous effects of old age on human muscle oxidative capacity in vivo: a systematic review and meta-analysis.

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    Fitzgerald, Liam F; Christie, Anita D; Kent, Jane A

    2016-11-01

    Despite intensive efforts to understand the extent to which skeletal muscle mitochondrial capacity changes in older humans, the answer to this important question remains unclear. To determine what the preponderance of evidence from in vivo studies suggests, we conducted a systematic review and meta-analysis of the effects of age on muscle oxidative capacity as measured noninvasively by magnetic resonance spectroscopy. A secondary aim was to examine potential moderators contributing to differences in results across studies, including muscle group, physical activity status, and sex. Candidate papers were identified from PubMed searches (n = 3561 papers) and the reference lists of relevant papers. Standardized effects (Hedges' g) were calculated for age and each moderator using data from the 22 studies that met the inclusion criteria (n = 28 effects). Effects were coded as positive when older (age, ≥55 years) adults had higher muscle oxidative capacity than younger (age, 20-45 years) adults. The overall effect of age on oxidative capacity was positive (g = 0.171, p < 0.001), indicating modestly greater oxidative capacity in old. Notably, there was significant heterogeneity in this result (Q = 245.8, p < 0.001; I(2) = ∼70%-90%). Muscle group, physical activity, and sex were all significant moderators of oxidative capacity (p ≤ 0.029). This analysis indicates that the current body of literature does not support a de facto decrease of in vivo muscle oxidative capacity in old age. The heterogeneity of study results and identification of significant moderators provide clarity regarding apparent discrepancies in the literature, and indicate the importance of accounting for these variables when examining purported age-related differences in muscle oxidative capacity.

  4. Estimation of age at death based on quantitation of the 4977-bp deletion of human mitochondrial DNA in skeletal muscle.

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    Meissner, C; von Wurmb, N; Schimansky, B; Oehmichen, M

    1999-11-01

    The 4977-bp deletion in human mitochondrial DNA (mtDNA) is known to accumulate in various tissues with age. Since this deletion in mtDNA correlates closest with age in muscle tissue, iliopsoas muscle tissue was taken at autopsy from 50 persons aged 24-97 years to determine whether age at death can be estimated based on the amount of the 4977-bp deletion in skeletal muscle. Total DNA (nuclear and mtDNA) was extracted from 100 mg tissue and the 4977-bp deletion quantified using a kinetic polymerase chain reaction (PCR) followed by visualization of the products on silver stained polyacrylamide gels. The amount of the 4977-bp deletion of mtDNA ranged from 0.00049% to 0.14% depending on age, with a correlation coefficient of r = 0.83 (P = 0.0001). In forensic practice this method can aid in the estimation of age at death with a relatively wide confidence interval, thus enabling a discrimination between young and elderly persons in the identification of human remains based solely on skeletal muscle.

  5. Detection of age-related duplications in mtDNA from human muscles and bones.

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    Lacan, Marie; Thèves, Catherine; Keyser, Christine; Farrugia, Audrey; Baraybar, Jose-Pablo; Crubézy, Eric; Ludes, Bertrand

    2011-03-01

    Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification.

  6. The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure.

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    Crane, Justin D; Devries, Michaela C; Safdar, Adeel; Hamadeh, Mazen J; Tarnopolsky, Mark A

    2010-02-01

    The purpose of this study was to determine whether ultrastructural changes in intramyocellular lipid (IMCL) and mitochondria occur with aging. Muscle samples were analyzed from 24 young and 20 old, equally active, individuals for IMCL and mitochondria quantity and size as well as their association. Old men had larger IMCL droplets than all other groups in the total muscle area. Old individuals showed higher IMCL content in the subsarcolemmal area. Young participants had a greater number of mitochondria compared with old participants in both fiber regions and greater enzyme activities of cytochrome c oxidase and citrate synthase. The fraction of IMCL touching mitochondria was lowest in old women in the total area and in old men in the subsarcolemmal region. In summary, older adults have larger IMCL droplets, fewer mitochondria, and a lower proportion of IMCL in contact with mitochondria. These factors likely contribute to age-related reductions in mitochondrial function and lipid metabolism.

  7. Folic acid ingestion improves skeletal muscle blood flow during graded handgrip and plantar flexion exercise in aged humans.

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    Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Moralez, Gilbert; Kouda, Ken; Jaffery, Manall F; Cramer, Matthew N; Crandall, Craig G

    2017-09-01

    Skeletal muscle blood flow is attenuated in aged humans performing dynamic exercise, which is due, in part, to impaired local vasodilatory mechanisms. Recent evidence suggests that folic acid improves cutaneous vasodilation during localized and whole body heating through nitric oxide-dependent mechanisms. However, it is unclear whether folic acid improves vasodilation in other vascular beds during conditions of increased metabolism (i.e., exercise). The purpose of this study was to test the hypothesis that folic acid ingestion improves skeletal muscle blood flow in aged adults performing graded handgrip and plantar flexion exercise via increased vascular conductance. Nine healthy, aged adults (two men and seven women; age: 68 ± 5 yr) performed graded handgrip and plantar flexion exercise before (control), 2 h after (acute, 5 mg), and after 6 wk (chronic, 5 mg/day) folic acid ingestion. Forearm (brachial artery) and leg (superficial femoral artery) blood velocity and diameter were measured via Duplex ultrasonography and used to calculate blood flow. Acute and chronic folic acid ingestion increased serum folate (both P < 0.05 vs. control). During handgrip exercise, acute and chronic folic acid ingestion increased forearm blood flow (both conditions P < 0.05 vs. control) and vascular conductance (both P < 0.05 vs. control). During plantar flexion exercise, acute and chronic folic acid ingestion increased leg blood flow (both P < 0.05 vs. control), but only acute folic acid ingestion increased vascular conductance (P < 0.05 vs. control). Taken together, folic acid ingestion increases blood flow to active skeletal muscle primarily via improved local vasodilation in aged adults.NEW & NOTEWORTHY Our findings demonstrate that folic acid ingestion improves blood flow via enhanced vascular conductance in the exercising skeletal muscle of aged humans. These findings provide evidence for the therapeutic use of folic acid to improve skeletal muscle blood flow, and perhaps

  8. Roles of sedentary aging and lifelong physical activity in exchange of glutathione across exercising human skeletal muscle.

    Science.gov (United States)

    Nyberg, Michael; Mortensen, Stefan P; Cabo, Helena; Gomez-Cabrera, Mari-Carmen; Viña, Jose; Hellsten, Ylva

    2014-08-01

    Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant system. Aging is associated with accumulation of oxidative damage to lipids, DNA, and proteins. Given the pro-oxidant effect of skeletal muscle contractions, this effect of age could be a result of excessive ROS formation. We evaluated the effect of acute exercise on changes in blood redox state across the leg of young (23 ± 1 years) and older (66 ± 2 years) sedentary humans by measuring the whole blood concentration of the reduced (GSH) and oxidized (GSSG) forms of the antioxidant glutathione. To assess the role of physical activity, lifelong physically active older subjects (62 ± 2 years) were included. Exercise increased the venous concentration of GSSG in an intensity-dependent manner in young sedentary subjects, suggesting an exercise-induced increase in ROS formation. In contrast, venous GSSG levels remained unaltered during exercise in the older sedentary and active groups despite a higher skeletal muscle expression of the superoxide-generating enzyme NADPH oxidase. Arterial concentration of GSH and expression of antioxidant enzymes in skeletal muscle of older active subjects were increased. The potential impairment in exercise-induced ROS formation may be an important mechanism underlying skeletal muscle and vascular dysfunction with sedentary aging. Lifelong physical activity upregulates antioxidant systems, which may be one of the mechanisms underlying the lack of exercise-induced increase in GSSG. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression.

    Directory of Open Access Journals (Sweden)

    Tipwadee Bunprajun

    Full Text Available Both aging and physical inactivity are associated with increased development of insulin resistance whereas physical activity has been shown to promote increased insulin sensitivity. Here we investigated the effects of physical activity level on aging-associated insulin resistance in myotubes derived from human skeletal muscle satellite cells. Satellite cells were obtained from young (22 yrs normally active or middle-aged (56.6 yrs individuals who were either lifelong sedentary or lifelong active. Both middle-aged sedentary and middle-aged active myotubes had increased p21 and myosin heavy chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane. On the other hand, middle-aged active cells retained both insulin-stimulated increases in glucose uptake and GLUT4 translocation to the plasma membrane. Middle-aged active cells also had significantly higher mRNA expression of GLUT1 and GLUT4 compared to middle-aged sedentary cells, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact on the metabolism of human myotubes during aging and may contribute to aging-associated insulin resistance through impaired GLUT4 localization.

  10. Lack of age-related increase of mitochondrial DNA amount in brain, skeletal muscle and human heart.

    Science.gov (United States)

    Frahm, Thomas; Mohamed, Salaheldien A; Bruse, Petra; Gemünd, Christine; Oehmichen, Manfred; Meissner, Christoph

    2005-11-01

    During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and other mutations have been reported. These structural alterations of mtDNA are assumed to cause a reduction in the respiratory chain activity and may contribute to the ageing process. Therefore, the question arises if the accumulation of deleted mtDNA is compensated in vivo by an increase of mtDNA synthesis via a feedback mechanism. We designed two human mtDNA-specific oligonucleotide probes for quantitative mtDNA analysis of 5 different tissues from 50 individuals aged from 8 weeks to 93 years. The amount of mtDNA was approximately 1.1 +/- 0.5% (4617 +/- 2099 copies) in the caudate nucleus, 1.0 +/- 0.5% (4198 +/- 2099 copies) in the frontal lobe cortex, 0.3 +/- 0.2% (1259 +/- 840 copies) in the cerebellar cortex, 1.0 +/- 0.4% (4198 +/- 1679 copies) in skeletal muscle and 2.2+/-1.3% (9235 +/- 5457 copies) in heart muscle. We did not observe any significant change in the absolute copy number during ageing in five different tissues, and therefore, found no evidence for the postulated feedback mechanism. Our study indicates that mtDNA copy number is tissue-specific and depends on the energy demand of the tissue.

  11. GAPDH and β-actin protein decreases with aging, making Stain-Free technology a superior loading control in Western blotting of human skeletal muscle

    DEFF Research Database (Denmark)

    Vigelsø Hansen, Andreas; Dybboe, Rie; Hansen, Christina Neigaard

    2015-01-01

    physiology where the intervention has been suggested to impede normalization (ageing, muscle atrophy, and different muscle fiber type composition). The linearity of signal and the methodological variation coefficient was obtained. Furthermore, the inter- and intraindividual variation in signals obtained from...... SF and RP was measured in relation to ageing, muscle atrophy, and different muscle fiber type composition, respectively. A stronger linearity of SF and β-actin compared with GAPDH and α-tubulin was observed. The methodological variation was relatively low in all four methods (4-11%). Protein level...... and differences in muscle fiber type. The novel SF technology adds lower variation to the results compared with the existing methods for correcting for loading inaccuracy in Western blotting of human skeletal muscle in applied physiology....

  12. Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle

    DEFF Research Database (Denmark)

    Suetta, C.; Frandsen, Ulrik; Mackey, Abigail

    2013-01-01

    expression analysis of key growth and transcription factors associated with local skeletal muscle milieu were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of re-training. OM demonstrated no detectable gains in MFA (VL muscle) and no increases in number of Pax7......Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and old human subjects subsequent to 2 weeks of immobility......-induced muscle atrophy. Re-training consisted of 4 weeks of supervised resistive exercise in 9 older (OM: 67.3yrs, range 61-74) and 11 young (YM: 24.4yrs, range 21-30) males. Measures of myofiber area (MFA), Pax7-positive satellite cells (SC) associated with type I and type II muscle fibres, as well as gene...

  13. Satellite cells in human skeletal muscle plasticity.

    Science.gov (United States)

    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

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

  14. Oxidative proteome alterations during skeletal muscle ageing

    Directory of Open Access Journals (Sweden)

    Sofia Lourenço dos Santos

    2015-08-01

    Full Text Available Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.

  15. AGE/RAGE promotes thecalcification of human aortic smooth muscle cells via the Wnt/β-catenin axis.

    Science.gov (United States)

    Liu, Yong; Wang, Wei-Ming; Zhang, Xue-Lin; He, Hu-Qiang; Sun, Xiao-Lei; Zeng, Hong; Xu, Xiong-Fei; Huang, Liang; Zhu, Zhi; Zhang, Lei; Zhou, Xiang-Yu; He, Yan-Zheng

    2016-01-01

    The present study aims to investigate whether RAGE promotes the calcification of human arterial smooth muscle cells (HASMCs) and determine the relationshipbetween RAGE and the Wnt/β-catenin signaling pathway in this process. In this study,there were four groups, namelythe blank control group, the non-transfection group, the empty vector group, and the RAGE transfection group.Cells were co-cultured with 10 mmol/L β-glycerophosphoric acid, pyruvate and 20 mg/L AGE. The expression of osteogenic proteins in each group before and after the intervention wasdetected using Western blotting. Short interfering RNA (siRNA) targeting β-catenin was used toinhibitthe expression of β-catenin. HASMCs cultured under normal conditions were usedas the blank control. (1) High RAGE expression was successfully induced in HASMCs according to the results of GFP detection, flow cytometry and Western blotting. (2) Compared with the blank control group, non-transfection group and empty vector group, RAGE transfection enhanced the calcification of cells when incubated with calcification medium plus AGE. (3) The expression of RAGE, β-catenin, OPG and Cbfa1 proteins in the blank control group, empty vector group and RAGE transfection group wasnot significantly enhanced after intervention. However, expression of the proteins in the RAGE transfection group was much higher than those of the other groups. (4) Compared with the RAGE transfection group and control siRNA group, the cells transfected with β-catenin siRNA and cultured with interventional drugs showed significant inhibition of the expression of the downstream Cbfa1 and OPG genes. Increased expression of RAGE promoted calcification in HASMCs and up regulated the β-catenin, OPG and Cbfa1 genes. RAGE may activate the downstream genes via the Wntβ-catenin pathway, thereby promoting HASMC differentiation into osteogenic cells and calcification.

  16. Aging related changes in determinants of muscle force generating capacity: a comparison of muscle aging in men and male rodents.

    Science.gov (United States)

    Ballak, Sam B; Degens, Hans; de Haan, Arnold; Jaspers, Richard T

    2014-03-01

    Human aging is associated with a progressive decline in skeletal muscle mass and force generating capacity, however the exact mechanisms underlying these changes are not fully understood. Rodents models have often been used to enhance our understanding of mechanisms of age-related changes in human skeletal muscle. However, to what extent age-related alterations in determinants of muscle force generating capacity observed in rodents resemble those in humans has not been considered thoroughly. This review compares the effect of aging on muscle force generating determinants (muscle mass, fiber size, fiber number, fiber type distribution and muscle specific tension), in men and male rodents at similar relative age. It appears that muscle aging in male F344*BN rat resembles that in men most; 32-35-month-old rats exhibit similar signs of muscle weakness to those of 70-80-yr-old men, and the decline in 36-38-month-old rats is similar to that in men aged over 80 yrs. For male C57BL/6 mice, age-related decline in muscle force generating capacity seems to occur only at higher relative age than in men. We conclude that the effects on determinants of muscle force differ between species as well as within species, but qualitatively show the same pattern as that observed in men.

  17. Roles of sedentary aging and lifelong physical activity on exchange of glutathione across exercising human skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Cabo, Helena

    2014-01-01

    muscle expression of the superoxide generating enzyme NADPH oxidase. Arterial concentration of GSH and expression of antioxidant enzymes in skeletal muscle of older active subjects was found to be increased. The potential impairment in exercise-induced ROS formation may be an important mechanism......Reactive oxygen species (ROS) are important signaling molecules with regulatory functions, and in young and adult organisms, the formation of ROS is increased during skeletal muscle contractions. However, ROS can be deleterious to cells when not sufficiently counterbalanced by the antioxidant...... the leg of young (23±1 years) and older (66±2 years) sedentary humans by measuring the whole blood concentration of the reduced (GSH) and oxidized (GSSG) form of the antioxidant glutathione. To assess the role of physical activity, lifelong physically active older subjects (62±2 years) were included...

  18. Exercise Promotes Healthy Aging of Skeletal Muscle

    DEFF Research Database (Denmark)

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M

    2016-01-01

    caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial...... respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle....

  19. Investigation of age-related changes in LMNA splicing and expression of progerin in human skeletal muscles

    OpenAIRE

    Luo, Yue-Bei; Mitrpant, Chalermchai; Johnsen, Russell D; Fabian, Victoria A; Fletcher, Sue; Mastaglia, Frank L.; Steve D Wilton

    2013-01-01

    Age-related changes in splice-forms of LMNA, which encodes the nuclear lamina proteins lamin A/C, have not been investigated in skeletal muscle. In the rare premature ageing disease, Hutchinson-Gilford progeria syndrome (HGPS), de novo point mutations in LMNA activate a cryptic splice site in exon 11, resulting in a 150 base deletion in LMNA mRNA and accumulation of a truncated protein isoform, progerin. The LMNA Δ150 progerin transcript has also been found in trace quantities in tissues of h...

  20. Premature aging in skeletal muscle lacking serum response factor.

    Directory of Open Access Journals (Sweden)

    Charlotte Lahoute

    Full Text Available Aging is associated with a progressive loss of muscle mass, increased adiposity and fibrosis that leads to sarcopenia. At the molecular level, muscle aging is known to alter the expression of a variety of genes but very little is known about the molecular effectors involved. SRF (Serum Response Factor is a crucial transcription factor for muscle-specific gene expression and for post-natal skeletal muscle growth. To assess its role in adult skeletal muscle physiology, we developed a post-mitotic myofiber-specific and tamoxifen-inducible SRF knockout model. Five months after SRF loss, no obvious muscle phenotype was observed suggesting that SRF is not crucial for myofiber maintenance. However, mutant mice progressively developed IIB myofiber-specific atrophy accompanied by a metabolic switch towards a more oxidative phenotype, muscular lipid accumulation, sarcomere disorganization and fibrosis. After injury, mutant muscles exhibited an altered regeneration process, showing smaller regenerated fibers and persistent fibrosis. All of these features are strongly reminiscent of abnormalities encountered in aging skeletal muscle. Interestingly, we also observed an important age associated decrease in SRF expression in mice and human muscles. Altogether, these results suggest that a naturally occurring SRF down-regulation precedes and contributes to the muscle aging process. Indeed, triggering SRF loss in the muscles of mutant mice results in an accelerated aging process.

  1. Lifelong physical activity prevents an age-related reduction in arterial and skeletal muscle nitric oxide bioavailability in humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Blackwell, James R; Damsgaard, Ramsus;

    2012-01-01

    Ageing has been proposed to be associated with increased levels of reactive oxygen species (ROS) that scavenge nitric oxide (NO). In eight young sedentary (23±1 years; Y), eight older lifelong sedentary (66±2 years; OS) and eight older lifelong physically active subjects (62±2 years; OA), we...... circulation and in the musculature of sedentary ageing humans due to increased oxidative stress. Lifelong physical activity opposes this effect within the trained musculature and in the arterial circulation. The lower blood flow response to leg exercise in ageing humans is not associated with a reduced...

  2. Amino acids in healthy aging skeletal muscle.

    Science.gov (United States)

    Riddle, Emily S; Stipanuk, Martha H; Thalacker-Mercer, Anna E

    2016-01-01

    Life expectancy in the U.S. and globally continues to increase. Despite increased life expectancy quality of life is not enhanced, and older adults often experience chronic age-related disease and functional disability, including frailty. Additionally, changes in body composition such as the involuntary loss of skeletal muscle mass (i.e. sarcopenia) and subsequent increases in adipose tissue can augment disease and disability in this population. Furthermore, increased oxidative stress and decreased antioxidant concentrations may also lead to metabolic dysfunction in older adults. Specific amino acids, including leucine, cysteine and its derivative taurine, and arginine can play various roles in healthy aging, especially in regards to skeletal muscle health. Leucine and arginine play important roles in muscle protein synthesis and cell growth while cysteine and arginine play important roles in quenching oxidative stress. Evidence suggests that supplemental doses of each of these amino acids may improve the aging phenotype. However, additional research is required to establish the doses required to achieve positive outcomes in humans.

  3. The Human Skeletal Muscle Proteome Project

    DEFF Research Database (Denmark)

    Gonzalez-Freire, Marta; Semba, Richard D.; Ubaida-Mohien, Ceereena

    2017-01-01

    Skeletal muscle is a large organ that accounts for up to half the total mass of the human body. A progressive decline in muscle mass and strength occurs with ageing and in some individuals configures the syndrome of ‘sarcopenia’, a condition that impairs mobility, challenges autonomy, and is a risk...... factor for mortality. The mechanisms leading to sarcopenia as well as myopathies are still little understood. The Human Skeletal Muscle Proteome Project was initiated with the aim to characterize muscle proteins and how they change with ageing and disease. We conducted an extensive review...... of the literature and analysed publically available protein databases. A systematic search of peer-reviewed studies was performed using PubMed. Search terms included ‘human’, ‘skeletal muscle’, ‘proteome’, ‘proteomic(s)’, and ‘mass spectrometry’, ‘liquid chromatography-mass spectrometry (LC-MS/MS)’. A catalogue...

  4. Trichinella spiralis in human muscle (image)

    Science.gov (United States)

    This is the parasite Trichinella spiralis in human muscle tissue. The parasite is transmitted by eating undercooked ... produce large numbers of larvae that migrate into muscle tissue. The cysts may cause muscle pain and ...

  5. Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model

    OpenAIRE

    2014-01-01

    As humans age, they lose both muscle mass and strength (sarcopenia). Testosterone, a circulating hormone, progressively declines in aging and is associated with loss of muscle mass and strength. Joining of a young and old mouse (heterochronic parabiosis) activates Notch signaling and restores muscle regenerative potential in aged mice. We hypothesize that testosterone is at least one of the factor required for the improvement seen in muscles in old mice in heterochronic parabiosis with young ...

  6. Genetically enhancing mitochondrial antioxidant activity improves muscle function in aging.

    Science.gov (United States)

    Umanskaya, Alisa; Santulli, Gaetano; Xie, Wenjun; Andersson, Daniel C; Reiken, Steven R; Marks, Andrew R

    2014-10-21

    Age-related skeletal muscle dysfunction is a leading cause of morbidity that affects up to half the population aged 80 or greater. Here we tested the effects of increased mitochondrial antioxidant activity on age-dependent skeletal muscle dysfunction using transgenic mice with targeted overexpression of the human catalase gene to mitochondria (MCat mice). Aged MCat mice exhibited improved voluntary exercise, increased skeletal muscle specific force and tetanic Ca(2+) transients, decreased intracellular Ca(2+) leak and increased sarcoplasmic reticulum (SR) Ca(2+) load compared with age-matched wild type (WT) littermates. Furthermore, ryanodine receptor 1 (the sarcoplasmic reticulum Ca(2+) release channel required for skeletal muscle contraction; RyR1) from aged MCat mice was less oxidized, depleted of the channel stabilizing subunit, calstabin1, and displayed increased single channel open probability (Po). Overall, these data indicate a direct role for mitochondrial free radicals in promoting the pathological intracellular Ca(2+) leak that underlies age-dependent loss of skeletal muscle function. This study harbors implications for the development of novel therapeutic strategies, including mitochondria-targeted antioxidants for treatment of mitochondrial myopathies and other healthspan-limiting disorders.

  7. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression

    DEFF Research Database (Denmark)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla

    2013-01-01

    chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma...... membrane. On the other hand, middle-aged active cells retained both insulin-stimulated increases in glucose uptake and GLUT4 translocation to the plasma membrane. Middle-aged active cells also had significantly higher mRNA expression of GLUT1 and GLUT4 compared to middle-aged sedentary cells......, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact...

  8. GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.

    Science.gov (United States)

    Egerman, Marc A; Cadena, Samuel M; Gilbert, Jason A; Meyer, Angelika; Nelson, Hallie N; Swalley, Susanne E; Mallozzi, Carolyn; Jacobi, Carsten; Jennings, Lori L; Clay, Ieuan; Laurent, Gaëlle; Ma, Shenglin; Brachat, Sophie; Lach-Trifilieff, Estelle; Shavlakadze, Tea; Trendelenburg, Anne-Ulrike; Brack, Andrew S; Glass, David J

    2015-07-07

    Age-related frailty may be due to decreased skeletal muscle regeneration. The role of TGF-β molecules myostatin and GDF11 in regeneration is unclear. Recent studies showed an age-related decrease in GDF11 and that GDF11 treatment improves muscle regeneration, which were contrary to prior studies. We now show that these recent claims are not reproducible and the reagents previously used to detect GDF11 are not GDF11 specific. We develop a GDF11-specific immunoassay and show a trend toward increased GDF11 levels in sera of aged rats and humans. GDF11 mRNA increases in rat muscle with age. Mechanistically, GDF11 and myostatin both induce SMAD2/3 phosphorylation, inhibit myoblast differentiation, and regulate identical downstream signaling. GDF11 significantly inhibited muscle regeneration and decreased satellite cell expansion in mice. Given early data in humans showing a trend for an age-related increase, GDF11 could be a target for pharmacologic blockade to treat age-related sarcopenia.

  9. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression

    DEFF Research Database (Denmark)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla

    2013-01-01

    , and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact...

  10. Esterase profile of human masseter muscle

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D; Vilmann, H

    1988-01-01

    The esterase profile of fresh human masseter muscle was investigated by use of histochemistry and electrophoresis. The histochemical methods included reactions for alpha-naphthyl esterase, myofibrillar ATPase, reverse myofibrillar ATPase and succinic dehydrogenase. In frozen sections of the muscl...

  11. The effect of age on rat rotator cuff muscle architecture.

    Science.gov (United States)

    Swan, Malcolm A; Sato, Eugene; Galatz, Leesa M; Thomopoulos, Stavros; Ward, Samuel R

    2014-12-01

    Understanding rotator cuff muscle function during disease development and after repair is necessary for preventing degeneration and improving postsurgical outcomes, respectively. The rat is a commonly used rotator cuff animal model; however, unlike humans, rats continue to grow throughout their lifespan, so age-related changes in muscle structure may complicate an understanding of muscle adaptations to injury. Infraspinatus and supraspinatus muscle mass, fiber length, pennation angle, sarcomere length, and physiological cross-sectional area (PCSA) were measured in Sprague-Dawley rats (n = 30) with a body mass ranging from 51 to 814 g (approximately 3 weeks to approximately 18 months). Both the supraspinatus and infraspinatus showed a striking conservation of sarcomere length throughout growth. There was linear growth in muscle mass and PCSA, nonlinear growth in muscle length and fiber bundle length, and a linear relationship between humeral head diameter and fiber bundle length, suggesting that muscle fiber length (serial sarcomere number) adjusted according to skeletal dimensions. These muscle growth trajectories allowed sarcomere length to remain nearly constant. During the typical rat rotator cuff experimental period (animal mass, 400-600 g), muscle mass will increase by 30%, fiber length will increase by 7%, and PCSA will increase by 27%, but sarcomere lengths are nearly constant. Therefore, these normal growth-induced changes in architecture must be considered when muscle atrophy or fiber shortening is measured after rotator cuff tears in this model. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  12. Fat Replacement of Paraspinal Muscles with Aging in Healthy Adults.

    Science.gov (United States)

    Dahlqvist, Julia R; Vissing, Christoffer R; Hedermann, Gitte; Thomsen, Carsten; Vissing, John

    2017-03-01

    The aims of this study were to investigate the age-related changes in fatty replacement and cross-sectional area (CSA) of cervical, thoracic, and lumbar paraspinal muscles versus leg muscles in healthy adults and to test for association between muscle fat fraction and lifestyle factors. Fifty-three healthy adults (24-76 yr) were included. Dixon magnetic resonance imaging technique was used to determine CSA and to quantify the fat fraction of paraspinal and leg muscles. Muscle CSA and fat fractions were tested for association with age and muscle strength. The fat fractions were also tested for association with sex, body mass index (BMI), physical activity, and lower back pain. Both paraspinal and leg fat fractions correlated directly with age (P fat fraction was higher in paraspinal than leg muscles. The age-related increase in fat fraction was higher in paraspinal muscles than leg muscles (P muscles did not correlate with age. Knee extension strength correlated with fat fraction (P muscle strength of hip muscles, thigh muscles, and anterior calf muscles correlated with CSA (P fat fraction (P fat fraction (P fat fraction and physical activity or lower back pain. The paraspinal muscles were more susceptible to age-related changes than leg muscles. Further, men had significantly lower fat fractions in lumbar paraspinal muscles, and BMI was positively associated with thigh, but not paraspinal, fat fraction.

  13. Muscle spindles in the human bulbospongiosus and ischiocavernosus muscles.

    Science.gov (United States)

    Peikert, Kevin; May, Christian Albrecht

    2015-07-01

    Muscle spindles are crucial for neuronal regulation of striated muscles, but their presence and involvement in the superficial perineal muscles is not known. Bulbospongiosus and ischiocavernosus muscle specimens were obtained from 31 human cadavers. Serial sections were stained with hematoxylin and eosin, Sirius red, antibodies against Podocalyxin, myosin heavy chain isoforms (MyHC-slow tonic, S46; MyHC-2a/2x, A4.74), and neurofilament for the purpose of muscle spindle screening, counting, and characterization. A low but consistent number of spindles were detected in both muscles. The muscles contained few intrafusal fibers, but otherwise showed normal spindle morphology. The extrafusal fibers of both muscles were small in diameter. The presence of muscle spindles in bulbospongiosus and ischiocavernosus muscles supports physiological models of pelvic floor regulation and may provide a basis for further clinical observations regarding sexual function and micturition. The small number of muscle spindles points to a minor level of proprioceptive regulation. © 2014 Wiley Periodicals, Inc.

  14. Biodemography of human ageing

    DEFF Research Database (Denmark)

    Vaupel, James W

    2010-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...... to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival...... - and healthy survival - to even greater ages....

  15. Muscle biopsy as a tool in the study of aging.

    Science.gov (United States)

    Coggan, A R

    1995-11-01

    The needle biopsy procedure provides a minimally invasive means of obtaining small samples of skeletal muscle from human volunteers. Such samples can be used to examine a variety of structural and functional characteristics of muscle, including fiber type and size, capillarization, enzymatic capacities, energy substrate or protein/mRNA concentrations, metabolic responses, and contractile properties. In conjunction with other methods, biopsy sampling can also be used to estimate total muscle mass and fiber number, and to determine rates of protein synthesis and degradation. Optimal handling and storage conditions vary widely, but in general, most of the above measurements can be made using frozen tissue, so that samples can be stored almost indefinitely. The procedure is also safe and generally well-tolerated, making it possible to perform longitudinal studies of the same person. The biopsy technique is therefore well suited for examining the underlying physiological mechanisms responsible for muscle wasting in the elderly, as well as for assessing the effects of nutritional, hormonal, and/or lifestyle (e.g., exercise) interventions intended to combat this problem. Although sample size limitations have been largely overcome by the development of microtechniques, more information is needed on how to minimize the variability introduced by studying only a small fraction of the whole muscle. Studies are also required to determine whether it is sufficient to biopsy only one muscle (and if so, which is optimal), or whether there are differential effects of aging in various muscle groups that would preclude extrapolating from one muscle to all muscles in the body.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Mitochondrial theory of aging in human age-related sarcopenia.

    Science.gov (United States)

    Parise, Gianni; De Lisio, Michael

    2010-01-01

    Understanding age-related sarcopenia and, more importantly, devising counterstrategies require an intimate knowledge of the underlying mechanism(s) of sarcopenia. The mitochondrial theory of aging (MTA) has been a leading theory on aging for the last decade; however, there is relatively little information from human tissue to support or rebut the involvement of the MTA in aging skeletal muscle. It is believed that mitochondria may contribute to sarcopenia in a stochastic fashion where regions of fibers containing dysfunctional mitochondria are forced to atrophy. Resistance exercise, a known hypertrophic stimulus, has been shown to improve the mitochondrial phenotype of aged skeletal muscle. Furthermore, activation of skeletal muscle stem cells by resistance exercise may attenuate sarcopenia in two ways. First by inducing nuclear addition to postmitotic fibers, and, second, by increasing the proportion of functional mitochondria donated by muscle stem cells in a process termed 'gene shifting'. In this chapter we review the evidence supporting the MTA, the potential to attenuate the MTA with a known hypertrophic stimuli and explore the role of muscle stem cells in gene shifting to determine the connection between mitochondrial dysfunction and age-related sarcopenia. Copyright © 2010 S. Karger AG, Basel.

  17. Increased Plin2 Expression in Human Skeletal Muscle Is Associated with Sarcopenia and Muscle Weakness

    Science.gov (United States)

    Conte, Maria; Vasuri, Francesco; Trisolino, Giovanni; Bellavista, Elena; Santoro, Aurelia; Degiovanni, Alessio; Martucci, Ermanno; D’Errico-Grigioni, Antonia; Caporossi, Daniela; Capri, Miriam; Maier, Andrea B.; Seynnes, Olivier; Barberi, Laura; Musarò, Antonio; Narici, Marco V.; Franceschi, Claudio; Salvioli, Stefano

    2013-01-01

    Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL) muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength. PMID:23977392

  18. Increased Plin2 expression in human skeletal muscle is associated with sarcopenia and muscle weakness.

    Directory of Open Access Journals (Sweden)

    Maria Conte

    Full Text Available Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2. It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength.

  19. A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging

    DEFF Research Database (Denmark)

    Anvar, Seyed Yahya; Raz, Yotam; Verway, Nisha

    2013-01-01

    Oculopharyngeal muscular dystrophy (OPMD) is caused by trinucleotide repeat expansion mutations in Poly(A) binding protein 1 (PABPN1). PABPN1 is a regulator of mRNA stability and is ubiquitously expressed. Here we investigated how symptoms in OPMD initiate only at midlife and why a subset...... of skeletal muscles is predominantly affected. Genome-wide RNA expression profiles from Vastus lateralis muscles human carriers of expanded-PABPN1 at pre-symptomatic and symptomatic stages were compared with healthy controls. Major expression changes were found to be associated with age rather than...... with expression of expanded-PABPN1, instead transcriptomes of OPMD and elderly muscles were significantly similar (P...

  20. Age- and gender-related changes in contractile properties of non-atrophied EDL muscle.

    Directory of Open Access Journals (Sweden)

    Stephen Chan

    Full Text Available BACKGROUND: In humans, ageing causes skeletal muscles to become atrophied, weak, and easily fatigued. In rodent studies, ageing has been associated with significant muscle atrophy and changes in the contractile properties of the muscles. However, it is not entirely clear whether these changes in contractile properties can occur before there is significant atrophy, and whether males and females are affected differently. METHODS AND RESULTS: We investigated various contractile properties of whole isolated fast-twitch EDL muscles from adult (2-6 months-old and aged (12-22 months-old male and female mice. Atrophy was not present in the aged mice. Compared with adult mice, EDL muscles of aged mice had significantly lower specific force, longer tetanus relaxation times, and lower fatiguability. In the properties of absolute force and muscle relaxation times, females were affected by ageing to a greater extent than males. Additionally, EDL muscles from a separate group of male mice were subjected to eccentric contractions of 15% strain, and larger force deficits were found in aged than in adult mice. CONCLUSION: Our findings provide further insight into the muscle atrophy, weakness and fatiguability experienced by the elderly. We have shown that even in the absence of muscle atrophy, there are definite alterations in the physiological properties of whole fast-twitch muscle from ageing mice, and for some of these properties the alterations are more pronounced in female mice than in male mice.

  1. Age- and Gender-Related Changes in Contractile Properties of Non-Atrophied EDL Muscle

    Science.gov (United States)

    Chan, Stephen; Head, Stewart I.

    2010-01-01

    Background In humans, ageing causes skeletal muscles to become atrophied, weak, and easily fatigued. In rodent studies, ageing has been associated with significant muscle atrophy and changes in the contractile properties of the muscles. However, it is not entirely clear whether these changes in contractile properties can occur before there is significant atrophy, and whether males and females are affected differently. Methods and Results We investigated various contractile properties of whole isolated fast-twitch EDL muscles from adult (2–6 months-old) and aged (12–22 months-old) male and female mice. Atrophy was not present in the aged mice. Compared with adult mice, EDL muscles of aged mice had significantly lower specific force, longer tetanus relaxation times, and lower fatiguability. In the properties of absolute force and muscle relaxation times, females were affected by ageing to a greater extent than males. Additionally, EDL muscles from a separate group of male mice were subjected to eccentric contractions of 15% strain, and larger force deficits were found in aged than in adult mice. Conclusion Our findings provide further insight into the muscle atrophy, weakness and fatiguability experienced by the elderly. We have shown that even in the absence of muscle atrophy, there are definite alterations in the physiological properties of whole fast-twitch muscle from ageing mice, and for some of these properties the alterations are more pronounced in female mice than in male mice. PMID:20808812

  2. Patterns of age-associated degeneration differ in shoulder muscles

    Directory of Open Access Journals (Sweden)

    Yotam eRaz

    2015-12-01

    Full Text Available Shoulder complaints are common in the elderly and hamper daily functioning. These complaints are often caused by tears in the muscle-tendon units of the rotator cuff (RC. The four RC muscles stabilize the shoulder joint. While some RC muscles are frequently torn in shoulder complaints others remain intact. The pathological changes in RC muscles are poorly understood. We investigated changes in RC muscle pathology combining radiological and histological procedures. We measured cross sectional area (CSA and fatty infiltration from Magnetic Resonance Imaging with Arthrography in subjects without (N=294 and with (N=109 RC-tears. Normalized muscle CSA of the four RC muscles and the deltoid shoulder muscle were compared and age-associated patterns of muscle atrophy and fatty infiltration were constructed. We identified two distinct age-associated patterns: in the supraspinatus and subscapularis RC muscles CSAs continuously declined throughout adulthood, whereas in the infraspinatus and deltoid reduced CSA was prominent from midlife onwards. In the teres minor, CSA was unchanged with age. Most importantly, age-associated patterns were highly similar between subjects without RC tear and those with RC-tears. This suggests that extensive RC muscle atrophy during aging could contribute to RC pathology. We compared muscle pathology between torn infraspinatus and non-torn teres minor and the deltoid in two patients with a massive RC-tear. In the torn infraspinatus we found pronounced fatty droplets, an increase in extracellular collagen-1, a loss of myosin heavy chain-1 expression in myofibers and an increase in Pax7-positive cells. However, the adjacent intact teres minor and deltoid exhibited healthy muscle features. This suggests that satellite cells and the extracellular matrix may contribute to extensive muscle fibrosis in torn RC. We suggest that torn RC muscles display hallmarks of muscle aging whereas the teres minor could represent an aging

  3. Patterns of Age-Associated Degeneration Differ in Shoulder Muscles

    Science.gov (United States)

    Raz, Yotam; Henseler, Jan F.; Kolk, Arjen; Riaz, Muhammad; van der Zwaal, Peer; Nagels, Jochem; Nelissen, Rob G. H. H.; Raz, Vered

    2015-01-01

    Shoulder complaints are common in the elderly and hamper daily functioning. These complaints are often caused by tears in the muscle-tendon units of the rotator cuff (RC). The four RC muscles stabilize the shoulder joint. While some RC muscles are frequently torn in shoulder complaints others remain intact. The pathological changes in RC muscles are poorly understood. We investigated changes in RC muscle pathology combining radiological and histological procedures. We measured cross sectional area (CSA) and fatty infiltration from Magnetic Resonance Imaging with Arthrography (MRA) in subjects without (N = 294) and with (N = 109) RC-tears. Normalized muscle CSA of the four RC muscles and the deltoid shoulder muscle were compared and age-associated patterns of muscle atrophy and fatty infiltration were constructed. We identified two distinct age-associated patterns: in the supraspinatus and subscapularis RC muscles CSAs continuously declined throughout adulthood, whereas in the infraspinatus and deltoid reduced CSA was prominent from midlife onwards. In the teres minor, CSA was unchanged with age. Most importantly, age-associated patterns were highly similar between subjects without RC tear and those with RC-tears. This suggests that extensive RC muscle atrophy during aging could contribute to RC pathology. We compared muscle pathology between torn infraspinatus and non-torn teres minor and the deltoid in two patients with a massive RC-tear. In the torn infraspinatus we found pronounced fatty droplets, an increase in extracellular collagen-1, a loss of myosin heavy chain-1 expression in myofibers and an increase in Pax7-positive cells. However, the adjacent intact teres minor and deltoid exhibited healthy muscle features. This suggests that satellite cells and the extracellular matrix may contribute to extensive muscle fibrosis in torn RC. We suggest that torn RC muscles display hallmarks of muscle aging whereas the teres minor could represent an aging

  4. Patterns of Age-Associated Degeneration Differ in Shoulder Muscles.

    Science.gov (United States)

    Raz, Yotam; Henseler, Jan F; Kolk, Arjen; Riaz, Muhammad; van der Zwaal, Peer; Nagels, Jochem; Nelissen, Rob G H H; Raz, Vered

    2015-01-01

    Shoulder complaints are common in the elderly and hamper daily functioning. These complaints are often caused by tears in the muscle-tendon units of the rotator cuff (RC). The four RC muscles stabilize the shoulder joint. While some RC muscles are frequently torn in shoulder complaints others remain intact. The pathological changes in RC muscles are poorly understood. We investigated changes in RC muscle pathology combining radiological and histological procedures. We measured cross sectional area (CSA) and fatty infiltration from Magnetic Resonance Imaging with Arthrography (MRA) in subjects without (N = 294) and with (N = 109) RC-tears. Normalized muscle CSA of the four RC muscles and the deltoid shoulder muscle were compared and age-associated patterns of muscle atrophy and fatty infiltration were constructed. We identified two distinct age-associated patterns: in the supraspinatus and subscapularis RC muscles CSAs continuously declined throughout adulthood, whereas in the infraspinatus and deltoid reduced CSA was prominent from midlife onwards. In the teres minor, CSA was unchanged with age. Most importantly, age-associated patterns were highly similar between subjects without RC tear and those with RC-tears. This suggests that extensive RC muscle atrophy during aging could contribute to RC pathology. We compared muscle pathology between torn infraspinatus and non-torn teres minor and the deltoid in two patients with a massive RC-tear. In the torn infraspinatus we found pronounced fatty droplets, an increase in extracellular collagen-1, a loss of myosin heavy chain-1 expression in myofibers and an increase in Pax7-positive cells. However, the adjacent intact teres minor and deltoid exhibited healthy muscle features. This suggests that satellite cells and the extracellular matrix may contribute to extensive muscle fibrosis in torn RC. We suggest that torn RC muscles display hallmarks of muscle aging whereas the teres minor could represent an aging

  5. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

    Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

    2012-01-01

    and adipose tissue leptin release in vivo. We recruited 16 healthy male human participants. Catheters were inserted into the femoral artery and vein draining skeletal muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose tissue. By combining the veno-arterial differences in plasma......Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... leptin with measurements of blood flow, leptin release from both tissues was quantified. To induce changes in leptin, the participants were infused with either saline or adrenaline in normo-physiological concentrations. The presence of leptin in skeletal muscle was confirmed by western blotting. Leptin...

  6. Lactate oxidation in human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Meinild, Anne-Kristine; Nordsborg, Nikolai B

    2013-01-01

    Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver, and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we...... analyze the ability of skeletal muscle to respire lactate by using an in situ mitochondrial preparation that leaves the native tubular reticulum and subcellular interactions of the organelle unaltered. Skeletal muscle biopsies were obtained from vastus lateralis muscle in 16 human subjects. Samples were...... of exogenous LDH failed to increase lactate-stimulated respiration (P = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within...

  7. Muscle quality in aging: a multi-dimensional approach to muscle functioning with applications for treatment.

    Science.gov (United States)

    Fragala, Maren S; Kenny, Anne M; Kuchel, George A

    2015-05-01

    Aging is often accompanied by declines in physical functioning which impedes older adults' quality of life, sense of independence, and ability to perform daily tasks. Age-related decreases in skeletal muscle quantity, termed sarcopenia, have traditionally been blamed for these physical decrements. However, recent evidence suggests that the quality of muscle tissue may be more functionally relevant than its quantity. 'Muscle quality' has been emerging as a means to elucidate and describe the intricate intramuscular changes associated with muscle performance in the context of aging and sarcopenia. While muscle quality has most commonly been defined in terms of muscle composition or relative strength, at the core, muscle quality really describes muscle's ability to function. Skeletal muscle displays a strong structure-function relationship by which several architectural characteristics factor into its functional capacity. This review describes the structural, physiological, and functional determinants of muscle quality at the tissue and cellular level, while also introducing other novel parameters such as sarcomere spacing and integrity, circulating biomarkers, and the muscle quality index. Muscle qualitative features are described from the perspective of how physical exercise may improve muscle quality in older adults. This broad, multidimensional perspective of muscle quality in the context of aging and sarcopenia offers comprehensive insights for consideration and integration in developing improved prognostic tools for research and clinical care, while also promoting translational approaches to the design of novel targeted intervention strategies designed to maintain function and mobility into late life.

  8. Age-associated repression of type 1 inositol 1, 4, 5-triphosphate receptor impairs muscle regeneration

    Science.gov (United States)

    Lee, Bora; Lee, Seung-Min; Bahn, Young Jae; Lee, Kwang-Pyo; Kang, Moonkyung; Kim, Yeon-Soo; Woo, Sun-Hee; Lim, Jae-Young; Kim, Eunhee; Kwon, Ki-Sun

    2016-01-01

    Skeletal muscle mass and power decrease with age, leading to impairment of mobility and metabolism in the elderly. Ca2+ signaling is crucial for myoblast differentiation as well as muscle contraction through activation of transcription factors and Ca2+-dependent kinases and phosphatases. Ca2+ channels, such as dihydropyridine receptor (DHPR), two-pore channel (TPC) and inositol 1,4,5-triphosphate receptor (ITPR), function to maintain Ca2+ homeostasis in myoblasts. Here, we observed a significant decrease in expression of type 1 IP3 receptor (ITPR1), but not types 2 and 3, in aged mice skeletal muscle and isolated myoblasts, compared with those of young mice. ITPR1 knockdown using shRNA-expressing viruses in C2C12 myoblasts and tibialis anterior muscle of mice inhibited myotube formation and muscle regeneration after injury, respectively, a typical phenotype of aged muscle. This aging phenotype was associated with repression of muscle-specific genes and activation of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. ERK inhibition by U0126 not only induced recovery of myotube formation in old myoblasts but also facilitated muscle regeneration after injury in aged muscle. The conserved decline in ITPR1 expression in aged human skeletal muscle suggests utility as a potential therapeutic target for sarcopenia, which can be treated using ERK inhibition strategies. PMID:27658230

  9. Enhancement of aging rat laryngeal muscles with endogenous growth factor treatment.

    Science.gov (United States)

    Stemple, Joseph C; Andreatta, Richard D; Seward, Tanya S; Angadi, Vrushali; Dietrich, Maria; McMullen, Colleen A

    2016-05-01

    Clinical evidence suggests that laryngeal muscle dysfunction is associated with human aging. Studies in animal models have reported morphological changes consistent with denervation in laryngeal muscles with age. Life-long laryngeal muscle activity relies on cytoskeletal integrity and nerve-muscle communication at the neuromuscular junction (NMJ). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. We hypothesized that treatment with neurotrophin 4 (NTF4) would modify the morphology and functional innervation of aging rat laryngeal muscles. Fifty-six Fischer 344xBrown Norway rats (6- and 30-mo age groups) were used to evaluate to determine if NTF4, given systemically (n = 32) or directly (n = 24), would improve the morphology and functional innervation of aging rat thyroarytenoid muscles. Results demonstrate the ability of rat laryngeal muscles to remodel in response to neurotrophin application. Changes were demonstrated in fiber size, glycolytic capacity, mitochondrial, tyrosine kinase receptors (Trk), NMJ content, and denervation in aging rat thyroarytenoid muscles. This study suggests that growth factors may have therapeutic potential to ameliorate aging-related laryngeal muscle dysfunction.

  10. Human muscle proteins: analysis by two-dimensional electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Giometti, C.S.; Danon, M.J.; Anderson, N.G.

    1983-09-01

    Proteins from single frozen sections of human muscle were separated by two-dimensional gel electrophoresis and detected by fluorography or Coomassie Blue staining. The major proteins were identical in different normal muscles obtained from either sex at different ages, and in Duchenne and myotonic dystrophy samples. Congenital myopathy denervation atrophy, polymyositis, and Becker's muscular dystrophy samples, however, showed abnormal myosin light chain compositions, some with a decrease of fast-fiber myosin light chains and others with a decrease of slow-fiber light chains. These protein alterations did not correlate with any specific disease, and may be cause by generalized muscle-fiber damage.

  11.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  12. The accommodative ciliary muscle function is preserved in older humans

    Science.gov (United States)

    Tabernero, Juan; Chirre, Emmanuel; Hervella, Lucia; Prieto, Pedro; Artal, Pablo

    2016-05-01

    Presbyopia, the loss of the eye’s accommodation capability, affects all humans aged above 45–50 years old. The two main reasons for this to happen are a hardening of the crystalline lens and a reduction of the ciliary muscle functionality with age. While there seems to be at least some partial accommodating functionality of the ciliary muscle at early presbyopic ages, it is not yet clear whether the muscle is still active at more advanced ages. Previous techniques used to visualize the accommodation mechanism of the ciliary muscle are complicated to apply in the older subjects, as they typically require fixation stability during long measurement times and/or to have an ultrasound probe directly in contact with the eye. Instead, we used our own developed method based on high-speed recording of lens wobbling to study the ciliary muscle activity in a small group of pseudophakic subjects (around 80 years old). There was a significant activity of the muscle, clearly able to contract under binocular stimulation of accommodation. This supports a purely lenticular-based theory of presbyopia and it might stimulate the search for new solutions to presbyopia by making use of the remaining contraction force still presented in the aging eye.

  13. Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes

    Directory of Open Access Journals (Sweden)

    Kang Peter B

    2006-03-01

    Full Text Available Abstract Background Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. Methods Orthologous (whole, sub- transcriptome profiles were compared among four mouse-human transcriptome datasets: (M six muscle groups obtained from three mouse strains (wildtype, mdx, mdx5cv; (H1 biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2 four different control human muscle types obtained at autopsy; and (H3 12 different control human tissues (ten non-muscle. Results Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy. Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3, indicating this finding to be muscle specific. Conclusion This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled.

  14. Fat Replacement of Paraspinal Muscles with Aging in Healthy Adults

    DEFF Research Database (Denmark)

    Dahlqvist, Julia R; Vissing, Christoffer R; Hedermann, Gitte

    2017-01-01

    with sex, BMI, physical activity and lower back pain. RESULTS: Both paraspinal and leg fat fractions correlated directly with age (p... fat fraction (pphysical activity or lower back pain. CONCLUSION: The paraspinal muscles were more susceptible to age-related changes than leg muscles. Further, men had significantly lower fat fractions in lumbar paraspinal muscles and BMI.......0001). The CSA of the muscles did not correlate with age. Knee extension strength correlated with fat fraction (pSex was associated with lumbar paraspinal fat fraction (p

  15. Human Muscle Fatigue Model in Dynamic Motions

    CERN Document Server

    Ma, Ruina; Bennis, Fouad; Ma, Liang

    2012-01-01

    Human muscle fatigue is considered to be one of the main reasons for Musculoskeletal Disorder (MSD). Recent models have been introduced to define muscle fatigue for static postures. However, the main drawbacks of these models are that the dynamic effect of the human and the external load are not taken into account. In this paper, each human joint is assumed to be controlled by two muscle groups to generate motions such as push/pull. The joint torques are computed using Lagrange's formulation to evaluate the dynamic factors of the muscle fatigue model. An experiment is defined to validate this assumption and the result for one person confirms its feasibility. The evaluation of this model can predict the fatigue and MSD risk in industry production quickly.

  16. Influence of age on leptin induced skeletal muscle signaling

    DEFF Research Database (Denmark)

    Guadalupe Grau, Amelia; Larsen, Steen; Guerra, Borja

    2014-01-01

    Age associated fat mass accumulation could be due to dysregulation of leptin signaling in skeletal muscle. Thus, we investigated total protein expression and phosphorylation levels of the long isoform of the leptin receptor (OB-Rb), and leptin signaling through Janus Kinase 2 (JAK2)/signal...... skeletal muscle of different age....

  17. Regulation of muscle atrophy in aging and disease.

    Science.gov (United States)

    Vinciguerra, Manlio; Musaro, Antonio; Rosenthal, Nadia

    2010-01-01

    Muscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease.

  18. GLUT-3 expression in human skeletal muscle

    Science.gov (United States)

    Stuart, C. A.; Wen, G.; Peng, B. H.; Popov, V. L.; Hudnall, S. D.; Campbell, G. A.

    2000-01-01

    Muscle biopsy homogenates contain GLUT-3 mRNA and protein. Before these studies, it was unclear where GLUT-3 was located in muscle tissue. In situ hybridization using a midmolecule probe demonstrated GLUT-3 within all muscle fibers. Fluorescent-tagged antibody reacting with affinity-purified antibody directed at the carboxy-terminus demonstrated GLUT-3 protein in all fibers. Slow-twitch muscle fibers, identified by NADH-tetrazolium reductase staining, possessed more GLUT-3 protein than fast-twitch fibers. Electron microscopy using affinity-purified primary antibody and gold particle-tagged second antibody showed that the majority of GLUT-3 was in association with triads and transverse tubules inside the fiber. Strong GLUT-3 signals were seen in association with the few nerves that traversed muscle sections. Electron microscopic evaluation of human peripheral nerve demonstrated GLUT-3 within the axon, with many of the particles related to mitochondria. GLUT-3 protein was found in myelin but not in Schwann cells. GLUT-1 protein was not present in nerve cells, axons, myelin, or Schwann cells but was seen at the surface of the peripheral nerve in the perineurium. These studies demonstrated that GLUT-3 mRNA and protein are expressed throughout normal human skeletal muscle, but the protein is predominantly found in the triads of slow-twitch muscle fibers.

  19. Impact of vaginal parity and aging on the architectural design of pelvic floor muscles.

    Science.gov (United States)

    Alperin, Marianna; Cook, Mark; Tuttle, Lori J; Esparza, Mary C; Lieber, Richard L

    2016-09-01

    Vaginal delivery and aging are key risk factors for pelvic floor muscle dysfunction, which is a critical component of pelvic floor disorders. However, alterations in the pelvic floor muscle intrinsic structure that lead to muscle dysfunction because of childbirth and aging remain elusive. The purpose of this study was to determine the impact of vaginal deliveries and aging on human cadaveric pelvic floor muscle architecture, which is the strongest predictor of active muscle function. Coccygeus, iliococcygeus, and pubovisceralis were obtained from younger donors who were ≤51 years old, vaginally nulliparous (n = 5) and vaginally parous (n = 6) and older donors who were >51 years old, vaginally nulliparous (n = 6) and vaginally parous (n = 6), all of whom had no history of pelvic floor disorders. Architectural parameters, which are predictive of muscle's excursion and force-generating capacity, were determined with the use of validated methods. Intramuscular collagen content was quantified by hydroxyproline assay. Main effects of parity and aging and the interactions were determined with the use of 2-way analysis of variance, with Tukey's post-hoc testing and a significance level of .05. The mean age of younger and older donors differed by approximately 40 years (P = .001) but was similar between nulliparous and parous donors within each age group (P > .9). The median parity was 2 (range, 1-3) in younger and older vaginally parous groups (P = .7). The main impact of parity was increased fiber length in the more proximal coccygeus (P = .03) and iliococcygeus (P = .04). Aging changes manifested as decreased physiologic cross-sectional area across all pelvic floor muscles (P < .05), which substantially exceeded the age-related decline in muscle mass. The physiologic cross-sectional area was lower in younger vaginally parous, compared with younger vaginally nulliparous, pelvic floor muscles; however, the differences did not reach statistical significance

  20. Adaptability of elderly human muscles and tendons to increased loading.

    Science.gov (United States)

    Narici, Marco V; Maganaris, Constantinos N

    2006-04-01

    Senile sarcopenia, the loss of muscle mass associated with aging, is one of the main causes of muscle weakness and reduced locomotor ability in old age. Although this condition is mainly driven by neuropathic processes, nutritional, hormonal and immunological factors, as well as a reduction in physical activity, contribute to this phenomenon. Sarcopenia alone, however, does not fully account for the observed muscle weakness, as the loss of force is greater than that accounted for by the decrease in muscle size. As a consequence, a reduction in the force per unit area, both at single fibre and at whole muscle level, is observed. We recently suggested that at whole muscle level, this reduction in intrinsic force is the result of the combined effect of changes in (1) muscle architecture, (2) tendon mechanical properties, (3) neural drive (reduced agonist and increased antagonist muscle activity) and (4) single fibre-specific tension. Whereas several studies support the role of the last two factors in the loss of intrinsic muscle force with aging, alterations in muscle architecture and in tendon mechanical properties have also been shown to contribute to the above phenomenon. Indeed, sarcopenia of the human plantarflexors, represented by a 25% reduction in muscle volume, was found to be associated with a 10% reduction in fibre fascicle length and 13% reduction in pennation angle. These architectural alterations were accompanied by a 10% decrease in tendon stiffness, attributable to alterations in tendon material properties, as suggested by a 14% decrease in Young's modulus. Most of these changes may be reversed by 14 weeks of resistive training; both fibre fascicle length and tendon stiffness were found to be increased by 10 and 64%, respectively. Surprisingly, however, training had no effect on the estimated relative length-tension properties of the muscle, indicating that the effects of greater tendon stiffness and increased fascicle length cancelled out each other

  1. Effects of aging on mitochondrial function in skeletal muscle of American American Quarter Horses.

    Science.gov (United States)

    Li, Chengcheng; White, Sarah H; Warren, Lori K; Wohlgemuth, Stephanie E

    2016-07-01

    Skeletal muscle function, aerobic capacity, and mitochondrial (Mt) function have been found to decline with age in humans and rodents. However, not much is known about age-related changes in Mt function in equine skeletal muscle. Here, we compared fiber-type composition and Mt function in gluteus medius and triceps brachii muscle between young (age 1.8 ± 0.1 yr, n = 24) and aged (age 17-25 yr, n = 10) American Quarter Horses. The percentage of myosin heavy chain (MHC) IIX was lower in aged compared with young muscles (gluteus, P = 0.092; triceps, P = 0.012), while the percentages of MHC I (gluteus; P < 0.001) and MHC IIA (triceps; P = 0.023) were increased. Mass-specific Mt density, indicated by citrate synthase activity, was unaffected by age in gluteus, but decreased in aged triceps (P = 0.023). Cytochrome-c oxidase (COX) activity per milligram tissue and per Mt unit decreased with age in gluteus (P < 0.001 for both) and triceps (P < 0.001 and P = 0.003, respectively). Activity of 3-hydroxyacyl-CoA dehydrogenase per milligram tissue was unaffected by age, but increased per Mt unit in aged gluteus and triceps (P = 0.023 and P < 0.001, respectively). Mt respiration of permeabilized muscle fibers per milligram tissue was unaffected by age in both muscles. Main effects of age appeared when respiration was normalized to Mt content, with increases in LEAK, oxidative phosphorylation capacity, and electron transport system capacity (P = 0.038, P = 0.045, and P = 0.007, respectively), independent of muscle. In conclusion, equine skeletal muscle aging was accompanied by a shift in fiber-type composition, decrease in Mt density and COX activity, but preserved Mt respiratory function.

  2. Lifelong physical exercise delays age-associated skeletal muscle decline.

    Science.gov (United States)

    Zampieri, S; Pietrangelo, L; Loefler, S; Fruhmann, H; Vogelauer, M; Burggraf, S; Pond, A; Grim-Stieger, M; Cvecka, J; Sedliak, M; Tirpáková, V; Mayr, W; Sarabon, N; Rossini, K; Barberi, L; De Rossi, M; Romanello, V; Boncompagni, S; Musarò, A; Sandri, M; Protasi, F; Carraro, U; Kern, H

    2015-02-01

    Aging is usually accompanied by a significant reduction in muscle mass and force. To determine the relative contribution of inactivity and aging per se to this decay, we compared muscle function and structure in (a) male participants belonging to a group of well-trained seniors (average of 70 years) who exercised regularly in their previous 30 years and (b) age-matched healthy sedentary seniors with (c) active young men (average of 27 years). The results collected show that relative to their sedentary cohorts, muscle from senior sportsmen have: (a) greater maximal isometric force and function, (b) better preserved fiber morphology and ultrastructure of intracellular organelles involved in Ca(2+) handling and ATP production, (c) preserved muscle fibers size resulting from fiber rescue by reinnervation, and (d) lowered expression of genes related to autophagy and reactive oxygen species detoxification. All together, our results indicate that: (a) skeletal muscle of senior sportsmen is actually more similar to that of adults than to that of age-matched sedentaries and (b) signaling pathways controlling muscle mass and metabolism are differently modulated in senior sportsmen to guarantee maintenance of skeletal muscle structure, function, bioenergetic characteristics, and phenotype. Thus, regular physical activity is a good strategy to attenuate age-related general decay of muscle structure and function (ClinicalTrials.gov: NCT01679977).

  3. Noninvasive analysis of human neck muscle function

    Science.gov (United States)

    Conley, M. S.; Meyer, R. A.; Bloomberg, J. J.; Feeback, D. L.; Dudley, G. A.

    1995-01-01

    selected muscles that have been examined in human electromyographic studies. Neck muscle function and morphology can be studied at a detailed level using exercise-induced shifts in magnetic resonance images.

  4. Muscle spindle composition and distribution in human young masseter and biceps brachii muscles reveal early growth and maturation.

    Science.gov (United States)

    Osterlund, Catharina; Liu, Jing-Xia; Thornell, Lars-Eric; Eriksson, Per-Olof

    2011-04-01

    Significant changes in extrafusal fiber type composition take place in the human masseter muscle from young age, 3-7 years, to adulthood, in parallel with jaw-face skeleton growth, changes of dentitions and improvement of jaw functions. As motor and sensory control systems of muscles are interlinked, also the intrafusal fiber population, that is, muscle spindles, should undergo age-related changes in fiber type appearance. To test this hypothesis, we examined muscle spindles in the young masseter muscle and compared the result with previous data on adult masseter spindles. Also muscle spindles in the young biceps brachii muscle were examined. The result showed that muscle spindle composition and distribution were alike in young and adult masseter. As for the adult masseter, young masseter contained exceptionally large muscle spindles, and with the highest spindle density and most complex spindles found in the deep masseter portion. Hence, contrary to our hypothesis, masseter spindles do not undergo major morphological changes between young age and adulthood. Also in the biceps, young spindles were alike adult spindles. Taken together, the results showed that human masseter and biceps muscle spindles are morphologically mature already at young age. We conclude that muscle spindles in the human young masseter and biceps precede the extrafusal fiber population in growth and maturation. This in turn suggests early reflex control and proprioceptive demands in learning and maturation of jaw motor skills. Similarly, well-developed muscle spindles in young biceps reflect early need of reflex control in learning and performing arm motor behavior. Copyright © 2011 Wiley-Liss, Inc.

  5. Oculopharyngeal muscular dystrophy as a paradigm for muscle aging

    Directory of Open Access Journals (Sweden)

    Yotam eRaz

    2014-11-01

    Full Text Available Symptoms in late-onset neuromuscular disorders initiate only from midlife onwards and progress with age. These disorders are primarily determined by identified hereditable mutations, but their late-onset symptom manifestation is not fully understood. Here, we review recent research developments on the late-onset autosomal dominant oculopharyngeal muscular dystrophy (OPMD. OPMD is caused by an expansion mutation in the gene encoding for poly-adenylate RNA binding protein1 (PABPN1. The molecular pathogenesis for the disease is still poorly understood. Despite a ubiquitous expression of PABPN1, symptoms in OPMD are limited to skeletal muscles. We discuss recent studies showing that PABPN1 levels in skeletal muscles are lower compared with other tissues, and specifically in skeletal muscles, PABPN1 expression declines from midlife onwards. In OPMD, aggregation of expanded PABPN1 causes an additional decline in the level of the functional protein, which is associated with severe muscle weakness in OPMD. Reduced PABNPN1 expression in muscle cell culture causes myogenic defects, suggesting that PABPN1 loss-of-function causes muscle weakness in OPMD and in the elderly.Molecular signatures of OPMD muscles are similar to these of normal muscle aging, although expression trends progress faster in OPMD. We discuss a working hypothesis that aging-associated factors trigger late-onset symptoms in OPMD, and contribute to accelerated muscle weakness in OPMD. We focus on the pharyngeal and eyelid muscles, which are often affected in OPMD patients. We suggest that muscle weakness in OPMD is a paradigm for muscle aging.

  6. Anisotropic photon migration in human skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Binzoni, T [Departement de Neurosciences Fondamentales, University of Geneva (Switzerland); Department of Radiology, University Hospital, Geneva (Switzerland); Courvoisier, C [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Giust, R [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Tribillon, G [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Gharbi, T [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Hebden, J C [Department of Medical Physics and Bioengineering, University College London (United Kingdom); Leung, T S [Department of Medical Physics and Bioengineering, University College London (United Kingdom); Roux, J [Hamamatsu Photonics, Grenoble (France); Delpy, D T [Department of Medical Physics and Bioengineering, University College London (United Kingdom)

    2006-03-07

    It is demonstrated in the short head of the human biceps brachii of 16 healthy subjects (12 males and 4 females) that near infrared photon migration is anisotropic. The probability for a photon to travel along the direction of the muscle fibres is higher ({approx}0.4) than that of travelling along a perpendicular axis ({approx}0.3) while in the adipose tissue the probability is the same ({approx}0.33) in all directions. Considering that the muscle fibre orientation is different depending on the type of muscle considered, and that inside a given skeletal muscle the orientation may change, the present findings in part might explain the intrasubject variability observed in the physiological parameters measured by near infrared spectroscopy techniques. In other words, the observed regional differences might not only be physiological differences but also optical artefacts. (note)

  7. Does skeletal muscle have an 'epi'-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise.

    Science.gov (United States)

    Sharples, Adam P; Stewart, Claire E; Seaborne, Robert A

    2016-08-01

    Skeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can 'remember' early-life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an 'epi'-memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re-encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early-life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise-induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the 'epi'-memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging.

  8. Muscle pain: animal and human experimental and clinical studies.

    Science.gov (United States)

    Marchettini, P

    1993-10-01

    The search for the identification of the sensory apparatus encoding muscle pain sensation in humans is recounted. Basic neurophysiologic animal studies, leading to a description of slowly conducting afferent from muscle and definition of high threshold polymodal muscle nociceptors, and pioneer psychophysic human studies together with recent microneurographic experiments in humans are described. The phenomena of muscle pain broad localization and distant referral are discussed, and clinical implications are extrapolated to interpret muscle pain as a localizing sign of mononeuropathy or radiculopathy. The identification of human muscle nociceptors has defined the scientific standard to test emerging clinical descriptions having muscle pain as a symptom.

  9. Skeletal muscle responses to unweighting in humans

    Science.gov (United States)

    Dudley, Gary A.

    1991-01-01

    An overview of earth-based studies is presented emphasizing the data on muscular strength and size derived from experiments under simulated microgravity. The studies involve the elimination of weight-bearing responsibility of lower-limb human musculature to simulate the unweighting effects of space travel in the absence of exercise. Reference is given to bedrest and unilateral lower-limb suspension, both of which provide data that demonstrate the decreased strength of the knee extensors of 20-25 percent. The response is related to the decrease in cross-sectional area of the knee extensors which is a direct indication of muscle-fiber atrophy. Most of the effects of unweighting are associated with extensor muscles in the lower limbs and not with postural muscles. Unweighting is concluded to cause significant adaptations in the human neuromuscular system that require further investigation.

  10. Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model.

    Science.gov (United States)

    Sinha, Indranil; Sinha-Hikim, Amiya P; Wagers, Amy J; Sinha-Hikim, Indrani

    2014-09-01

    As humans age, they lose both muscle mass and strength (sarcopenia). Testosterone, a circulating hormone, progressively declines in aging and is associated with loss of muscle mass and strength. The surgical joining of a young and old mouse (heterochronic parabiosis) activates Notch signaling and restores muscle regenerative potential in aged mice. We hypothesize that testosterone is at least one of the factors required for the improvement seen in muscles in old mice in heterochronic parabiosis with young mice. To test this hypothesis, we established the following heterochronic parabioses between young (Y; 5 months old) and old (O; 22-23 months old) C57BL6 male mice: (1) Y:O; (2) castrated Y:O (ØY:O); (3) castrated + testosterone-treated Y:O (ØY + T:O). A group of normal young mice received empty implants, and old mice were used as controls. Parabiotic pairings were maintained for 4 weeks prior to analysis. Serum testosterone levels were three-fold higher in young than in old mice. The ØY + T:O pairing demonstrated significantly elevated levels of serum testosterone and an improvement in gastrocnemius muscle weight, muscle ultrastructure, muscle fiber cross-sectional area, and Notch-1 expression in old mice. These changes were not present in aged mice in the ØY:O pairing. These data indicate that testosterone has a critical role in mediating the improved muscle mass and ultrastructure seen in an experimental model of heterochronic parabiosis.

  11. Modeling human muscle disease in zebrafish

    OpenAIRE

    Guyon, Jeffrey R.; Steffen, Leta S; Howell, Melanie H.; Pusack, Timothy J; Lawrence, Chris; Kunkel, Louis M

    2007-01-01

    Modeling human muscle disease in zebrafish correspondence: Corresponding author. Children's Hospital Boston, Enders Bldg, Rm 570, 300 Longwood Ave Boston, MA 02115. Tel.: +1 617 355 7576. (Kunkel, Louis M.) (Kunkel, Louis M.) Program in Genomics and Howard Hughes Medical Institute at Children's Hospital Boston - Boston--> , MA 02115--> - UNITED STATES (Guyon, Jeffrey R.) Program in Genomics a...

  12. Human Growth Hormone (HGH): Does It Slow Aging?

    Science.gov (United States)

    Healthy Lifestyle Healthy aging Human growth hormone is described by some as the key to slowing the aging process. Before you sign up, get the facts. ... stave off some of the changes linked to aging, such as decreased muscle and bone mass. If ...

  13. Age-related botulinum toxin effects on muscle fiber conduction velocity in non-injected muscles

    NARCIS (Netherlands)

    Lange, Fiete; van Weerden, Tiemen W.; van der Hoeven, Johannes H.

    2007-01-01

    Objective: We studied systemic effects of botulinum toxin (BTX) treatment on muscle fiber conduction velocity (MFCV) and possible effects of age. Methods: MFCV was determined by an invasive EMG method in the biceps brachii muscle. Seventeen BTX treated patients and 58 controls were investigated. BTX

  14. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models

    Directory of Open Access Journals (Sweden)

    Fabio Demontis

    2013-11-01

    Full Text Available A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.

  15. Therapeutic potential of eccentric exercises for age-related muscle atrophy

    Directory of Open Access Journals (Sweden)

    Jae-Young Lim

    2016-09-01

    Full Text Available Recent studies have focused on evidence-based interventions to prevent mobility decline and enhance physical performance in older adults. Several modalities, in addition to traditional strengthening programs, have been designed to manage age-related functional decline more effectively. In this study, we reviewed the current relevant literatures to assess the therapeutic potential of eccentric exercises for age-related muscle atrophy (sarcopenia. Age-related changes in human skeletal muscle, and their relationship with physical performance, are discussed with reference to in vitro physiologic and human biomechanics studies. An overview of issues relevant to sarcopenia is provided in the context of the recent consensus on the diagnosis and management of the condition. A decline in mobility among the aging population is closely linked with changes in the muscle force–velocity relationship. Interventions based specifically on increasing velocity and eccentric strength can improve function more effectively compared with traditional strengthening programs. Eccentric strengthening programs are introduced as a specific method for improving both muscle force and velocity. To be more effective, exercise interventions for older adults should focus on enhancing the muscle force–velocity relationship. Exercises that can be performed easily, and that utilize eccentric strength (which is relatively spared during the aging process, are needed to improve both muscle force and velocity.

  16. Regulation of Metabolic Signaling in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth

    sensitivity in type I muscle fibers possibly reflects a superior effect of insulin on metabolic signaling compared to type II muscle fibers. This was investigated in the present thesis by examining muscle biopsies from lean and obese healthy subjects as well as patients with type 2 diabetes. From these muscle...... enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance...... of human type I muscle fibers is illustrated by the finding of a positive correlation between the relative distribution of type I fibers in the muscle and whole-body insulin sensitivity. This suggests, that type I muscle fibers are more insulin sensitive than type II muscle fibers. Improved insulin...

  17. Decline in lumbar extensor muscle strength the older adults: correlation with age, gender and spine morphology

    OpenAIRE

    Singh, Devinder Kaur Ajit; Bailey, Martin; Lee, Raymond

    2013-01-01

    Background Muscle morphology, age and gender may be determinants of muscle strength in older adults. However, very few research studies have directly examined such correlation in the ageing spine. The aim of the study was to examine the correlation between lumbar extensor muscle strength, its muscle fibre angles, thoracolumbar curvature, age and gender in the older and younger adults. Methods Muscle fibre angles of lumbar extensor muscles, thoracolumbar curvature and lumbar extensor muscle st...

  18. Motor endplate cholinesterase in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Fujii,Masafumi

    1982-08-01

    Full Text Available The activity and properties of cholinesterase (ChE of the motor endplate and its fractions were studied in isolated human skeletal muscle. This preparation was used since the ChE activity of the membrane preparation was localized only in the motor endplate. The endplate ChE was stable in the isolated membrane for 4 weeks at 4 degrees C. The specific activity of the extracted ChE of human muscle membrane was 29.6% higher than that of the original membrane. Studies with specific substrates and ChE inhibitors indicated that most of the ChE of human muscle membrane and its fractions was acetylcholinesterase, and that the minor component was pseudocholinesterase. A Michaelis-Menten constant of 3.82 mM was estimated in the endplate ChE, and 0.88 mM in the extracted ChE of the endplate. The extracted human endplate ChE was separated into three fractions by Sephadex G-200 chromatography, and into two fractions by acrylamide gel electrophoresis.

  19. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

    Directory of Open Access Journals (Sweden)

    Barbora de Courten

    Full Text Available Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists.Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography, % body fat (bioimpedance, abdominal subcutaneous and visceral adiposity (magnetic resonance imaging, insulin sensitivity (euglycaemic hyperinsulinemic clamp, resting energy expenditure (REE, indirect calorimetry, free-living ambulatory physical activity (accelerometers and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04 and subcutaneous (r = 0.38, p = 0.02 but not visceral fat (r = 0.17, p = 0.33. Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008, REE (r = -0.58, p<0.001 and HDL-cholesterol levels (r = -0.34, p = 0.048. Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity.Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

  20. Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.

    Science.gov (United States)

    Cosgrove, Benjamin D; Gilbert, Penney M; Porpiglia, Ermelinda; Mourkioti, Foteini; Lee, Steven P; Corbel, Stephane Y; Llewellyn, Michael E; Delp, Scott L; Blau, Helen M

    2014-03-01

    The elderly often suffer from progressive muscle weakness and regenerative failure. We demonstrate that muscle regeneration is impaired with aging owing in part to a cell-autonomous functional decline in skeletal muscle stem cells (MuSCs). Two-thirds of MuSCs from aged mice are intrinsically defective relative to MuSCs from young mice, with reduced capacity to repair myofibers and repopulate the stem cell reservoir in vivo following transplantation. This deficiency is correlated with a higher incidence of cells that express senescence markers and is due to elevated activity of the p38α and p38β mitogen-activated kinase pathway. We show that these limitations cannot be overcome by transplantation into the microenvironment of young recipient muscles. In contrast, subjecting the MuSC population from aged mice to transient inhibition of p38α and p38β in conjunction with culture on soft hydrogel substrates rapidly expands the residual functional MuSC population from aged mice, rejuvenating its potential for regeneration and serial transplantation as well as strengthening of damaged muscles of aged mice. These findings reveal a synergy between biophysical and biochemical cues that provides a paradigm for a localized autologous muscle stem cell therapy for the elderly.

  1. Conjugated linoleic acid (CLA) prevents age associated skeletal muscle loss

    OpenAIRE

    Rahman, Md M; Halade, Ganesh V.; Jamali, Amina El; Fernandes, Gabriel

    2009-01-01

    In this study, we examined the effect of CLA isomers in preventing age-associated muscle loss and the mechanisms underlying this effect, using 12 months old C57BL/6 mice fed 10% corn oil (CO) or a diet supplemented with 0.5% c9t11-CLA, t10c12-CLA or c9t11-CLA+t10c12-CLA (CLA-mix) for 6 months. Both t10c12-CLA and CLA-mix groups showed significantly higher muscle mass, as compared to CO and c9t11-CLA groups, measured by dual-energy-Xray-absorptiometry and muscle wet weight. Enhanced mitochondr...

  2. Muscle wasting in myotonic dystrophies: a model of premature aging.

    Science.gov (United States)

    Mateos-Aierdi, Alba Judith; Goicoechea, Maria; Aiastui, Ana; Fernández-Torrón, Roberto; Garcia-Puga, Mikel; Matheu, Ander; López de Munain, Adolfo

    2015-01-01

    Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular

  3. Muscle wasting in myotonic dystrophies: a model of premature aging.

    Directory of Open Access Journals (Sweden)

    Alba Judith eMateos-Aierdi

    2015-07-01

    Full Text Available Myotonic dystrophy type I (DM1 or Steinert’s disease and type II (DM2 are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, and other clinical manifestations such as cardiomyopathy, insulin-resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc., including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTGn triplet expansion in the 3’ untranslated region of the DMPK gene, whereas (CCTGn repeats in the first intron of the CNBP/ZNF9 gene cause DM2. The expansions are transcribed into (CUGn and (CCUGn-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL, forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.

  4. Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity.

    Directory of Open Access Journals (Sweden)

    Grégory Lacraz

    Full Text Available Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs. Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM, which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.

  5. Aging changes in the bones - muscles - joints

    Science.gov (United States)

    Changes in posture and gait (walking pattern) are common with aging. Changes in the skin and hair are also common. The skeleton provides support and structure to the body. Joints are the areas where bones come together. They allow the ...

  6. Pericapillary basement membrane thickening in human skeletal muscles.

    Science.gov (United States)

    Baum, Oliver; Bigler, Marius

    2016-09-01

    The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases.

  7. Myofibre damage in human skeletal muscle

    DEFF Research Database (Denmark)

    Crameri, R M; Aagaard, P; Qvortrup, K

    2007-01-01

    Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation but not in hum......Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation...... but not in humans using voluntary exercise. Untrained males (n=8, range 22-27 years) performed 210 maximal eccentric contractions with each leg on an isokinetic dynamometer, voluntarily (VOL) with one leg and electrically induced (ES) with the other leg. Assessments from the skeletal muscle were obtained prior...... to exercise and at 5, 24, 96 and 192 h postexercise. Muscle tenderness rose in VOL and ES after 24 h, and did not differ between groups. Maximal isometric contraction strength, rate of force development and impulse declined in the VOL leg from 4 h after exercise, but not in ES (except at 24 h). In contrast...

  8. AGE IN NORMAL HUMAN PREGNANCY

    African Journals Online (AJOL)

    ABSTRACT. Normal human pregnancy (PREG) predisposes towards gestational age (GA) ... These results potently suggest that the HH changes observed in this study are of advantage to ... changes of physiological functions affecting all body.

  9. Effects of ageing on single muscle fibre contractile function following short-term immobilisation

    DEFF Research Database (Denmark)

    Hvid, Lars G; Ortenblad, Niels; Aagaard, Per;

    2011-01-01

    Very little attention has been given to the combined effects of healthy ageing and short-term disuse on the contractile function of human single muscle fibres. Therefore, the present study investigated the effects of 2 weeks of lower limb cast immobilisation (i.e. disuse) on selected contractile...

  10. Live strong and prosper: the importance of skeletal muscle strength for healthy ageing.

    Science.gov (United States)

    McLeod, Michael; Breen, Leigh; Hamilton, D Lee; Philp, Andrew

    2016-06-01

    Due to improved health care, diet and infrastructure in developed countries, since 1840 life expectancy has increased by approximately 2 years per decade. Accordingly, by 2050, a quarter of Europe's population will be over 65 years, representing a 10 % rise in half a century. With this rapid rise comes an increased prevalence of diseases of ageing and associated healthcare expenditure. To address the health consequences of global ageing, research in model systems (worms, flies and mice) has indicated that reducing the rate of organ growth, via reductions in protein synthetic rates, has multi-organ health benefits that collectively lead to improvements in lifespan. In contrast, human pre-clinical, clinical and large cohort prospective studies demonstrate that ageing leads to anabolic (i.e. growth) impairments in skeletal muscle, which in turn leads to reductions in muscle mass and strength, factors directly associated with mortality rates in the elderly. As such, increasing muscle protein synthesis via exercise or protein-based nutrition maintains a strong, healthy muscle mass, which in turn leads to improved health, independence and functionality. The aim of this review is to critique current literature relating to the maintenance of muscle mass across lifespan and discuss whether maintaining or reducing protein synthesis is the most logical approach to support musculoskeletal function and by extension healthy human ageing.

  11. Skeletal muscle bioenergetics in aging and heart failure.

    Science.gov (United States)

    Liu, Sophia Z; Marcinek, David J

    2017-03-01

    Changes in mitochondrial capacity and quality play a critical role in skeletal and cardiac muscle dysfunction. In vivo measurements of mitochondrial capacity provide a clear link between physical activity and mitochondrial function in aging and heart failure, although the cause and effect relationship remains unclear. Age-related decline in mitochondrial quality leads to mitochondrial defects that affect redox, calcium, and energy-sensitive signaling by altering the cellular environment that can result in skeletal muscle dysfunction independent of reduced mitochondrial capacity. This reduced mitochondrial quality with age is also likely to sensitize skeletal muscle mitochondria to elevated angiotensin or beta-adrenergic signaling associated with heart failure. This synergy between aging and heart failure could further disrupt cell energy and redox homeostasis and contribute to exercise intolerance in this patient population. Therefore, the interaction between aging and heart failure, particularly with respect to mitochondrial dysfunction, should be a consideration when developing strategies to improve quality of life in heart failure patients. Given the central role of the mitochondria in skeletal and cardiac muscle dysfunction, mitochondrial quality may provide a common link for targeted interventions in these populations.

  12. Obesity accelerates epigenetic aging of human liver.

    Science.gov (United States)

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T; Tsai, Pei-Chien; Spector, Tim D; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

  13. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  14. The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate intensity exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Vigelsø, Andreas; Gram, Martin; Dybboe, Rie

    2016-01-01

    Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks' unilateral leg immobilization on substrate utilization across the legs during moderate intensity exercise in young (n = 17;...

  15. Regional Differences in Muscle Energy Metabolism in Human Muscle by 31P-Chemical Shift Imaging.

    Science.gov (United States)

    Kime, Ryotaro; Kaneko, Yasuhisa; Hongo, Yoshinori; Ohno, Yusuke; Sakamoto, Ayumi; Katsumura, Toshihito

    2016-01-01

    Previous studies have reported significant region-dependent differences in the fiber-type composition of human skeletal muscle. It is therefore hypothesized that there is a difference between the deep and superficial parts of muscle energy metabolism during exercise. We hypothesized that the inorganic phosphate (Pi)/phosphocreatine (PCr) ratio of the superficial parts would be higher, compared with the deep parts, as the work rate increases, because the muscle fiber-type composition of the fast-type may be greater in the superficial parts compared with the deep parts. This study used two-dimensional 31Phosphorus Chemical Shift Imaging (31P-CSI) to detect differences between the deep and superficial parts of the human leg muscles during dynamic knee extension exercise. Six healthy men participated in this study (age 27±1 year, height 169.4±4.1 cm, weight 65.9±8.4 kg). The experiments were carried out with a 1.5-T superconducting magnet with a 5-in. diameter circular surface coil. The subjects performed dynamic one-legged knee extension exercise in the prone position, with the transmit-receive coil placed under the right quadriceps muscles in the magnet. The subjects pulled down an elastic rubber band attached to the ankle at a frequency of 0.25, 0.5 and 1 Hz for 320 s each. The intracellular pH (pHi) was calculated from the median chemical shift of the Pi peak relative to PCr. No significant difference in Pi/PCr was observed between the deep and the superficial parts of the quadriceps muscles at rest. The Pi/PCr of the superficial parts was not significantly increased with increasing work rate. Compared with the superficial areas, the Pi/PCr of the deep parts was significantly higher (p<0.05) at 1 Hz. The pHi showed no significant difference between the two parts. These results suggest that muscle oxidative metabolism is different between deep and superficial parts of quadriceps muscles during dynamic exercise.

  16. Role of the Cytokine-like Hormone Leptin in Muscle-bone Crosstalk with Aging

    Science.gov (United States)

    2017-01-01

    The cytokine-like hormone leptin is a classic adipokine that is secreted by adipocytes, increases with weight gain, and decreases with weight loss. Additional studies have, however, shown that leptin is also produced by skeletal muscle, and leptin receptors are abundant in both skeletal muscle and bone-derived mesenchymal (stromal) stem cells. These findings suggest that leptin may play an important role in muscle-bone crosstalk. Leptin treatment in vitro increases the expression of myogenic genes in primary myoblasts, and leptin treatment in vivo increases the expression of microRNAs involved in myogenesis. Bone marrow adipogenesis is associated with low bone mass in humans and rodents, and leptin can reduce marrow adipogenesis centrally through its receptors in the hypothalamus as well as directly via its receptors in bone marrow stem cells. Yet, central leptin resistance can increase with age, and low circulating levels of leptin have been observed among the frail elderly. Thus, aging appears to significantly alter leptin-mediated crosstalk among various organs and tissues. Aging is associated with bone loss and muscle atrophy, contributing to frailty, postural instability, and the incidence of falls. Therapeutic interventions such as protein and amino acid supplementation that can increase muscle mass and muscle-derived leptin may have multiple benefits for the elderly that can potentially reduce the incidence of falls and fractures. PMID:28326295

  17. Glucose transporter expression in human skeletal muscle fibers

    DEFF Research Database (Denmark)

    Gaster, M; Handberg, A; Beck-Nielsen, H

    2000-01-01

    amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation......, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas...... after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle...

  18. Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.

    NARCIS (Netherlands)

    Serlie, M.J.; Haan, J.H.A. de; Tack, C.J.J.; Verberne, H.J.; Ackermans, M.T.; Heerschap, A.; Sauerwein, H.P.

    2005-01-01

    The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

  19. Accelerated aging syndromes, are they relevant to normal human aging?

    Science.gov (United States)

    Dreesen, Oliver; Stewart, Colin L

    2011-09-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.

  20. Molecular biology of human muscle disease

    Energy Technology Data Exchange (ETDEWEB)

    Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

    1991-01-01

    The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

  1. Effect of age on fatty infiltration of supraspinatus muscle after experimental tendon release in rats

    Directory of Open Access Journals (Sweden)

    Farshad Mazda

    2011-12-01

    Full Text Available Abstract Background Rotator cuff tendon tear is a leading cause for atrophy, fibrosis and fatty infiltration of the rotator cuff muscles. The pathophysiology of fatty muscle infiltration is not well understood. An animal model suited to study cellular and molecular mechanisms would therefore be desirable. While a rat model has been established for chronic rotator cuff tendon pathology, sufficient and easily identifiable fatty infiltration of the muscle has not yet been shown in rats. As younger animals regenerate better, we hypothesized that the absence of a sufficient amount of fatty infiltration in previous experiments was due to the selection of young animals and that older animals would exhibit higher amounts of fatty infiltration after tendon tear. Findings The supraspinatus tendon was released using tenotomy in 3 young (6 weeks old and in 3 aged (24 months old Sprague Dawley rats (group I and II. Another 3 aged (24 months old rats underwent sham surgery and served as a control group (group III. In group I and II retraction of the musculotendinous unit was allowed for 6 weeks. All animals were sacrificed 6 weeks after surgery and the supraspinatus muscles were harvested. Each sample was examined for fatty infiltration of the muscle by histological methods and micro-CT. In histology, fat cells were counted with a 10-fold magnification in 6 fields of view twice. An adjusted measurement setup was developed for the use of micro-CT to quantify the absorption coefficient of the muscle as a reciprocal indicator for fatty infiltration, based on the established procedure for quantification of fatty infiltration on CT in humans. Tenotomy resulted in an insignificant increase of fat cells in histological sections in both, aged and young rats. Micro-CT was able to quantify small differences in the absorption coefficients of muscle samples; the absorption coefficient was 8.1% ± 11.3% lower in retracted muscles (group I and II compared with the control

  2. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle....... Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM...

  3. Regulation of Metabolic Signaling in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth

    Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic enz...... interval exercise). The abundance of signaling proteins and metabolic enzymes are in most cases different in type I and type II muscle fibers, indicating that their glucose metabolism is different.......Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic...... enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance...

  4. Xanthine oxidase in human skeletal muscle following eccentric exercise

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik; Orthenblad, N.

    1997-01-01

    1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one-legged eccentric exercise. Muscle biopsies from both the exercised and the ......1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one-legged eccentric exercise. Muscle biopsies from both the exercised...... the increase in xanthine oxidase in the muscle there were no detectable changes in the levels of muscle malondialdehyde or in plasma antioxidant capacity up to 4 days post-exercise. 5. It is concluded that eccentric exercise leads to an increased level of xanthine oxidase in human muscle and that the increase...

  5. Proteomic Profiling of Mitochondrial Enzymes during Skeletal Muscle Aging

    Directory of Open Access Journals (Sweden)

    Lisa Staunton

    2011-01-01

    Full Text Available Mitochondria are of central importance for energy generation in skeletal muscles. Expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis, fibre maturation, and various neuromuscular pathologies, as well as natural fibre aging. Mass spectrometry-based proteomics suggests itself as a convenient large-scale and high-throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease. This paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles. Changes in the abundance, biochemical activity, subcellular localization, and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel biomarkers of aging. In the long term, this may advance diagnostic procedures, improve the monitoring of disease progression, help in the testing of side effects due to new drug regimes, and enhance our molecular understanding of age-related muscle degeneration.

  6. Does growth hormone therapy in conjunction with resistance exercise increase muscle force production and muscle mass in men and women aged 60 years or older?

    Science.gov (United States)

    Zachwieja, J J; Yarasheski, K E

    1999-01-01

    Improved muscle protein mass and increments in maximum voluntary muscle force have rarely been observed in men and women aged 60 years and older who were treated with rhGH. Although rhGH administration has been reported to increase lean body mass in older men and women, it is doubtful that this increase is localized to skeletal muscle contractile proteins. When rhGH administration was combined with 16 weeks of resistance exercises, increases in muscle mass, muscle protein synthesis, and muscle force were not greater in the rhGH-treated group than in a weight training group that received placebo injections. Side effects of rhGH treatment in elderly people are prevalent, not trivial, and further limit its usefulness as an effective anabolic agent for promoting muscle protein accretion in men and women. In particular, the induction of insulin resistance and carpal tunnel compression reduces the efficacy of rhGH replacement therapy in elderly individuals. The evidence for a GH-induced increase in human skeletal muscle protein and maximum voluntary muscle force is weak. The optimum dose and GH-replacement paradigm (GHRH, GH-secretagogues) have not been identified. Whether rhGH therapy improves muscle protein mass and force in individuals with severe cachexia associated with major trauma, burns, surgery, or muscular dystrophy is controversial and under investigation.

  7. The expression of HSP in human skeletal muscle. Effects of muscle fiber phenotype and training background

    DEFF Research Database (Denmark)

    Folkesson, Mattias; Mackey, Abigail L; Langberg, Henning;

    2013-01-01

    AIM: Exercise-induced adaptations of skeletal muscle are related to training mode and can be muscle fibre type specific. This study aimed to investigate heat shock protein expression in type I and type II muscle fibres in resting skeletal muscle of subjects with different training backgrounds...... HSPs in human skeletal muscle is influenced by muscle fibre phenotype. The fibre type specific expression of HSP70 is influenced by resistance and endurance training whereas those of αB-crystallin and HSP27 are influenced only by endurance training suggesting the existence of a training......-modality specific action on the adaptive processes including heat shock proteins in human skeletal muscle. This article is protected by copyright. All rights reserved....

  8. Localization of nitric oxide synthase in human skeletal muscle

    DEFF Research Database (Denmark)

    Frandsen, Ulrik; Lopez-Figueroa, M.; Hellsten, Ylva

    1996-01-01

    The present study investigated the cellular localization of the neuronal type I and endothelial type III nitric oxide synthase in human skeletal muscle. Type I NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all muscle fibres. Stronger immunoreactivity was expressed...... I NO synthase immunoreactivity and NADPH diaphorase activity. Type III NO synthase immunoreactivity was observed both in the endothelium of larger vessels and of microvessels. The results establish that human skeletal muscle expresses two different constitutive isoforms of NO synthase in different...... endothelium is consistent with a role for NO in the control of blood flow in human skeletal muscle....

  9. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

    Larsen, Steen; Wright-Paradis, C; Gnaiger, E

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain...... loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples....... functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...

  10. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

    Larsen, S; Wright-Paradis, C; Gnaiger, E

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain...... functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...... loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples....

  11. Effects of aging on muscle mechanical function and muscle fiber morphology during short-term immobilization and subsequent retraining

    DEFF Research Database (Denmark)

    Hvid, Lars; Aagaard, Per; Justesen, Lene;

    2010-01-01

    Very little attention has been given to the combined effects of aging and disuse as separate factors causing deterioration in muscle mechanical function. Thus the purpose of this study was to investigate the effects of 2 wk of immobilization followed by 4 wk of retraining on knee extensor muscle...... to the deleterious effects of short-term muscle disuse on muscle fiber size and rapid force capacity than YM. Furthermore, OM seems to require longer time to recover and regain rapid muscle force capacity, which may lead to a larger risk of falling in aged individuals after periods of short-term disuse....

  12. Human skeletal muscle fibroblasts stimulate in vitro myogenesis and in vivo muscle regeneration.

    Science.gov (United States)

    Mackey, Abigail L; Magnan, Mélanie; Chazaud, Bénédicte; Kjaer, Michael

    2017-08-01

    Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. The extent of cross-talk between fibroblasts, as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell-culture studies. We observed a strong stimulation of myogenesis by human fibroblasts in cell culture. In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres. These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell-cell cross-talk during physiological and pathological muscle remodelling. Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle injury protocol in young healthy men (n = 7), the number of fibroblasts (TCF7L2+), satellite cells (Pax7+), differentiating myogenic cells (myogenin+) and regenerating fibres (neonatal/embryonic myosin+) was determined from biopsy cross-sections. Fibroblasts and myogenic precursor cells (MPCs) were also isolated from human skeletal muscle (n = 4) and co-cultured using different cell ratios, with the two cell populations either in direct contact with each other or separated by a permeable

  13. Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle

    Directory of Open Access Journals (Sweden)

    Anne Bigot

    2015-11-01

    Full Text Available The molecular mechanisms by which aging affects stem cell number and function are poorly understood. Murine data have implicated cellular senescence in the loss of muscle stem cells with aging. Here, using human cells and by carrying out experiments within a strictly pre-senescent division count, we demonstrate an impaired capacity for stem cell self-renewal in elderly muscle. We link aging to an increased methylation of the SPRY1 gene, a known regulator of muscle stem cell quiescence. Replenishment of the reserve cell pool was modulated experimentally by demethylation or siRNA knockdown of SPRY1. We propose that suppression of SPRY1 by age-associated methylation in humans inhibits the replenishment of the muscle stem cell pool, contributing to a decreased regenerative response in old age. We further show that aging does not affect muscle stem cell senescence in humans.

  14. Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle.

    Science.gov (United States)

    Bigot, Anne; Duddy, William J; Ouandaogo, Zamalou G; Negroni, Elisa; Mariot, Virginie; Ghimbovschi, Svetlana; Harmon, Brennan; Wielgosik, Aurore; Loiseau, Camille; Devaney, Joe; Dumonceaux, Julie; Butler-Browne, Gillian; Mouly, Vincent; Duguez, Stéphanie

    2015-11-10

    The molecular mechanisms by which aging affects stem cell number and function are poorly understood. Murine data have implicated cellular senescence in the loss of muscle stem cells with aging. Here, using human cells and by carrying out experiments within a strictly pre-senescent division count, we demonstrate an impaired capacity for stem cell self-renewal in elderly muscle. We link aging to an increased methylation of the SPRY1 gene, a known regulator of muscle stem cell quiescence. Replenishment of the reserve cell pool was modulated experimentally by demethylation or siRNA knockdown of SPRY1. We propose that suppression of SPRY1 by age-associated methylation in humans inhibits the replenishment of the muscle stem cell pool, contributing to a decreased regenerative response in old age. We further show that aging does not affect muscle stem cell senescence in humans.

  15. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    Science.gov (United States)

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

    Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  16. Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men.

    Science.gov (United States)

    Buford, Thomas W; Cooke, Matthew B; Manini, Todd M; Leeuwenburgh, Christiaan; Willoughby, Darryn S

    2010-05-01

    Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits p50 and p65. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKbeta. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

  17. Effects of Age and Sedentary Lifestyle on Skeletal Muscle NF-κB Signaling in Men

    Science.gov (United States)

    Buford, Thomas W.; Cooke, Matthew B.; Manini, Todd M.; Leeuwenburgh, Christiaan

    2010-01-01

    Background. Nuclear factor kappa B (NF-κB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. Methods. The present study examined lean mass, maximal force production, and skeletal muscle NF-κB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 ± 6.59 year), physically active (OA, N = 14, 60.71 ± 5.54 year), or young and sedentary (YS, N = 14, 21.35 ± 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the β subunit of IkB kinase (IKKβ), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBα), and nuclear content of NF-κB subunits p50 and p65. Results. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBα than OA and 61% more pIKBα than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKβ. Conclusions. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBα. A sedentary lifestyle appears to play some role in increased IKBα; however, further research is needed to identify downstream effects of this increase. PMID:20045871

  18. Age- and stroke-related skeletal muscle changes: a review for the geriatric clinician.

    Science.gov (United States)

    Sions, Jaclyn Megan; Tyrell, Christine M; Knarr, Brian A; Jancosko, Angela; Binder-Macleod, Stuart A

    2012-01-01

    Independently, aging and stroke each have a significant negative impact on skeletal muscle, but the potential cumulative effects of aging and stroke have not been explored. Optimal interventions for individuals post stroke may include those that specifically target skeletal muscle. Addressing changes in muscles may minimize activity limitations and enhance participation post stroke. This article reviews the impact of aging and stroke on muscle morphology and composition, including fiber atrophy, reductions in muscle cross-sectional area, changes in muscle fiber distributions, and increases in intramuscular fat. Relationships between changes in muscle structure, muscle function, and physical mobility are reviewed. Clinical recommendations that preserve and enhance skeletal muscle in the aging adult and individuals post stroke are discussed. Future research directions that include systematic comparison of the differences in skeletal muscle between younger and older adults who have sustained a stroke are suggested.

  19. Muscle fiber and motor unit behavior in the longest human skeletal muscle.

    Science.gov (United States)

    Harris, A John; Duxson, Marilyn J; Butler, Jane E; Hodges, Paul W; Taylor, Janet L; Gandevia, Simon C

    2005-09-14

    The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers.

  20. Common errors in textbook descriptions of muscle fiber size in nontrained humans.

    Science.gov (United States)

    Chalmers, Gordon R; Row, Brandi S

    2011-09-01

    Exercise science and human anatomy and physiology textbooks commonly report that type IIB muscle fibers have the largest cross-sectional area of the three fiber types. These descriptions of muscle fiber sizes do not match with the research literature examining muscle fibers in young adult nontrained humans. For men, most commonly type IIA fibers were significantly larger than other fiber types (six out of 10 cases across six different muscles). For women, either type I, or both I and IIA muscle fibers were usually significantly the largest (five out of six cases across four different muscles). In none of these reports were type IIB fibers significantly larger than both other fiber types. In 27 studies that did not include statistical comparisons of mean fiber sizes across fiber types, in no cases were type IIB or fast glycolytic fibers larger than both type I and IIA, or slow oxidative and fast oxidative glycolytic fibers. The likely reason for mistakes in textbook descriptions of human muscle fiber sizes is that animal data were presented without being labeled as such, and without any warning that there are interspecies differences in muscle fiber properties. Correct knowledge of muscle fiber sizes may facilitate interpreting training and aging adaptations.

  1. Nitric oxide availability is increased in contracting skeletal muscle from aged mice, but does not differentially decrease muscle superoxide.

    Science.gov (United States)

    Pearson, T; McArdle, A; Jackson, M J

    2015-01-01

    Reactive oxygen and nitrogen species have been implicated in the loss of skeletal muscle mass and function that occurs during aging. Nitric oxide (NO) and superoxide are generated by skeletal muscle and where these are generated in proximity their chemical reaction to form peroxynitrite can compete with the superoxide dismutation to hydrogen peroxide. Changes in NO availability may therefore theoretically modify superoxide and peroxynitrite activities in tissues, but published data are contradictory regarding aging effects on muscle NO availability. We hypothesised that an age-related increase in NO generation might increase peroxynitrite generation in muscles from old mice, leading to an increased nitration of muscle proteins and decreased superoxide availability. This was examined using fluorescent probes and an isolated fiber preparation to examine NO content and superoxide in the cytosol and mitochondria of muscle fibers from adult and old mice both at rest and following contractile activity. We also examined the 3-nitrotyrosine (3-NT) and peroxiredoxin 5 (Prx5) content of muscles from mice as markers of peroxynitrite activity. Data indicate that a substantial age-related increase in NO levels occurred in muscle fibers during contractile activity and this was associated with an increase in muscle eNOS. Muscle proteins from old mice also showed an increased 3-NT content. Inhibition of NOS indicated that NO decreased superoxide bioavailability in muscle mitochondria, although this effect was not age related. Thus increased NO in muscles of old mice was associated with an increased 3-NT content that may potentially contribute to age-related degenerative changes in skeletal muscle.

  2. Determination of human muscle protein fractional synthesis rate

    DEFF Research Database (Denmark)

    Bornø, Andreas; Hulston, Carl J; van Hall, Gerrit

    2014-01-01

    In the present study, different MS methods for the determination of human muscle protein fractional synthesis rate (FSR) using [ring-(13)C6 ]phenylalanine as a tracer were evaluated. Because the turnover rate of human skeletal muscle is slow, only minute quantities of the stable isotopically......-MS/MS) and GC-tandem MS (GC-MS/MS) have made these techniques an option for human muscle FSR measurements. Human muscle biopsies were freeze dried, cleaned, and hydrolyzed, and the amino acids derivatized using either N-acetyl-n-propyl, phenylisothiocyanate, or N.......89 ± 0.01, P muscle FSR, (2) LC-MS/MS comes quite close and is a good alternative when tissue quantities are too small for GC-C-IRMS, and (3) If GC-MS/MS is to be used, then the HFBA derivative should be used instead...

  3. Muscle fascicle strains in human gastrocnemius during backward downhill walking.

    Science.gov (United States)

    Hoffman, B W; Cresswell, A G; Carroll, T J; Lichtwark, G A

    2014-06-01

    Extensive muscle damage can be induced in isolated muscle preparations by performing a small number of stretches during muscle activation. While typically these fiber strains are large and occur over long lengths, the extent of exercise-induced muscle damage (EIMD) observed in humans is normally less even when multiple high-force lengthening actions are performed. This apparent discrepancy may be due to differences in muscle fiber and tendon dynamics in vivo; however, muscle and tendon strains have not been quantified during muscle-damaging exercise in humans. Ultrasound and an infrared motion analysis system were used to measure medial gastrocnemius fascicle length and lower limb kinematics while humans walked backward, downhill for 1 h (inducing muscle damage), and while they walked briefly forward on the flat (inducing no damage). Supramaximal tibial nerve stimulation, ultrasound, and an isokinetic dynamometer were used to quantify the fascicle length-torque relationship pre- and 2 h postexercise. Torque decreased ~23%, and optimal fascicle length shifted rightward ~10%, indicating that EIMD occurred during the damage protocol even though medial gastrocnemius fascicle stretch amplitude was relatively small (~18% of optimal fascicle length) and occurred predominantly within the ascending limb and plateau region of the length-torque curve. Furthermore, tendon contribution to overall muscle-tendon unit stretch was ~91%. The data suggest the compliant tendon plays a role in attenuating muscle fascicle strain during backward walking in humans, thus minimizing the extent of EIMD. As such, in situ or in vitro mechanisms of muscle damage may not be applicable to EIMD of the human gastrocnemius muscle. Copyright © 2014 the American Physiological Society.

  4. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

    2011-01-01

    The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging...

  5. Association of low back pain with muscle stiffness and muscle mass of the lumbar back muscles, and sagittal spinal alignment in young and middle-aged medical workers.

    Science.gov (United States)

    Masaki, Mitsuhiro; Aoyama, Tomoki; Murakami, Takashi; Yanase, Ko; Ji, Xiang; Tateuchi, Hiroshige; Ichihashi, Noriaki

    2017-09-14

    Muscle stiffness of the lumbar back muscles in low back pain (LBP) patients has not been clearly elucidated because quantitative assessment of the stiffness of individual muscles was conventionally difficult. This study aimed to examine the association of LBP with muscle stiffness assessed using ultrasonic shear wave elastography (SWE) and muscle mass of the lumbar back muscle, and spinal alignment in young and middle-aged medical workers. The study comprised 23 asymptomatic medical workers [control (CTR) group] and 9 medical workers with LBP (LBP group). Muscle stiffness and mass of the lumbar back muscles (lumbar erector spinae, multifidus, and quadratus lumborum) in the prone position were measured using ultrasonic SWE. Sagittal spinal alignment in the standing and prone positions was measured using a Spinal Mouse. The association with LBP was investigated by multiple logistic regression analysis with a forward selection method. The analysis was conducted using the shear elastic modulus and muscle thickness of the lumbar back muscles, and spinal alignment, age, body height, body weight, and sex as independent variables. Multiple logistic regression analysis showed that muscle stiffness of the lumbar multifidus muscle and body height were significant and independent determinants of LBP, but that muscle mass and spinal alignment were not. Muscle stiffness of the lumbar multifidus muscle in the LBP group was significantly higher than that in the CTR group. The results of this study suggest that LBP is associated with muscle stiffness of the lumbar multifidus muscle in young and middle-aged medical workers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle.

    Science.gov (United States)

    Macias, Beatriz; Gomez-Pinilla, Pedro J; Camello-Almaraz, Cristina; Pascua, Patricia; Tresguerres, Jesus Af; Camello, Pedro J; Pozo, Maria J

    2012-08-01

    Calcium sensitization is an important physiological process in agonist-induced contraction of smooth muscle. In brief, calcium sensitization is a pathway that leads to smooth muscle contraction independently of changes in [Ca(2+)](i) by mean of inhibition of myosin light chain phosphatase. Aging has negative impacts on gallbladder contractile response due to partial impairment in calcium signaling and alterations in the contractile machinery. However, information regarding aging-induced alterations in calcium sensitization is scanty. We hypothesized that the calcium sensitization system is negatively affected by age. To investigate this, gallbladders were collected from adult (4 months old) and aged (22-24 months old) guinea pigs. To evaluate the contribution of calcium sensitization pathways we assayed the effect of the specific inhibitors Y-27632 and GF109203X on the "in vitro" isometric gallbladder contractions induced by agonist challenges. In addition, expression and phosphorylation (as activation index) of proteins participating in the calcium sensitization pathways were quantified by Western blotting. Aging reduced bethanechol- and cholecystokinin-evoked contractions, an effect associated with a reduction in MLC20 phosphorylation and in the effects of both Y-27632 and GF109203X. In addition, there was a drop in ROCK I, ROCK II, MYPT-1 and PKC expression and in the activation/phosphorylation of MYPT-1, PKC and CPI-17 in response to agonists. Interestingly, melatonin treatment for 4 weeks restored gallbladder contractile responses due to re-establishment of calcium sensitization pathways. These results demonstrate that age-related gallbladder hypocontractility is associated to alterations of calcium sensitization pathways and that melatonin treatment exerts beneficial effects in the recovery of gallbladder contractility.

  7. Aging is not a barrier to muscle and redox adaptations: applying the repeated eccentric exercise model.

    Science.gov (United States)

    Nikolaidis, Michalis G; Kyparos, Antonios; Spanou, Chrysa; Paschalis, Vassilis; Theodorou, Anastasios A; Panayiotou, George; Grivas, Gerasimos V; Zafeiridis, Andreas; Dipla, Konstantina; Vrabas, Ioannis S

    2013-08-01

    Despite the progress of analytic techniques and the refinement of study designs, striking disagreement exists among studies regarding the influence of exercise on muscle function and redox homeostasis in the elderly. The repeated eccentric exercise model was applied to produce long-lasting and extensive changes in redox biomarkers and to reveal more effectively the potential effects of aging on redox homeostasis. Ten young (20.6±0.5 years) and ten elderly men (64.6±1.1 years) underwent an isokinetic eccentric exercise session, which was repeated after three weeks. Muscle function/damage indices (torque, range of movement, muscle soreness and creatine kinase) and redox biomarkers (F2-isoprostanes, protein carbonyls, glutathione, catalase, superoxide dismutase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, uric acid, bilirubin and albumin) were assessed in plasma, erythrocytes or urine pre-exercise, immediately post-exercise and at 2 and 4 days post-exercise. As expected, the elderly group exhibited oxidative stress in baseline compared to the young group. Extensive muscle damage and extensive alterations in redox homeostasis appeared after the first bout of eccentric exercise. Noteworthy, the redox responses were similar between the age groups despite their differences in baseline values. Likewise, both age groups demonstrated blunted alterations in muscle damage and redox homeostasis after the second bout of eccentric exercise indicating adaptations from the first bout of exercise. Elderly individuals seem to be well fitted to participate in demanding physical activities without suffering detrimental effects on skeletal muscle and/or disturbances on redox homeostasis. The repeated eccentric exercise model may be a useful and practical physiological tool to study redox biology in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Tirasemtiv amplifies skeletal muscle response to nerve activation in humans

    OpenAIRE

    Hansen,Richard; Saikali, Khalil G; Chou, Willis; Alan J Russell; Chen, Michael M.; Vijayakumar, Vipin; Stoltz, Randall R.; Baudry, Stephane; Enoka, Roger M.; Morgans, David J; Wolff, Andrew A.; Malik, Fady I

    2014-01-01

    Introduction: In this study we tested the hypothesis that tirasemtiv, a selective fast skeletal muscle troponin activator that sensitizes the sarcomere to calcium, could amplify the response of muscle to neuromuscular input in humans. Methods: Healthy men received tirasemtiv and placebo in a randomized, double-blind, 4-period, crossover design. The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot. The force–freque...

  9. Hormone Treatment and Muscle Anabolism during Aging: Androgens

    Science.gov (United States)

    Dillon, E. Lichar; Durham, William J.; Urban, Randall J.; Sheffield-Moore, Melinda

    2010-01-01

    Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood. The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use. Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women. PMID:20452103

  10. Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle

    DEFF Research Database (Denmark)

    Mounier, Rémi; Pedersen, Bente Klarlund; Plomgaard, Peter

    2010-01-01

    from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1...... a significantly higher VEGF protein content than vastus lateralis and triceps muscle. In conclusion, we have shown that there are muscle-specific differences in HIF-1alpha and VEGF expression within human skeletal muscle at rest in normoxic conditions. Recent results, when combined with the findings described...

  11. Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle

    DEFF Research Database (Denmark)

    1993-01-01

    report quantitative and qualitative changes in NCAM protein and mRNA forms during aging in normal rat skeletal muscle. Determination of the amount of NCAM by e.l.i.s.a. showed that the level decreased from perinatal to adult age, followed by a considerable increase in 24-month-old rat muscle. Thus NCAM...... virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2......Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here...

  12. Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Milène Catoire

    Full Text Available Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max. Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

  13. High efficiency in human muscle: an anomaly and an opportunity?

    Science.gov (United States)

    Nelson, Frank E; Ortega, Justus D; Jubrias, Sharon A; Conley, Kevin E; Kushmerick, Martin J

    2011-08-15

    Can human muscle be highly efficient in vivo? Animal muscles typically show contraction-coupling efficiencies FDI) muscle of the hand has an efficiency value in vivo of 68%. We examine two key factors that could account for this apparently high efficiency value: (1) transfer of cross-bridge work into mechanical work and (2) the use of elastic energy to do external work. Our analysis supports a high contractile efficiency reflective of nearly complete transfer of muscular to mechanical work with no contribution by recycling of elastic energy to mechanical work. Our survey of reported contraction-coupling efficiency values puts the FDI value higher than typical values found in small animals in vitro but within the range of values for human muscle in vivo. These high efficiency values support recent studies that suggest lower Ca(2+) cycling costs in working contractions and a decline in cost during repeated contractions. In the end, our analysis indicates that the FDI muscle may be exceptional in having an efficiency value on the higher end of that reported for human muscle. Thus, the FDI muscle may be an exception both in contraction-coupling efficiency and in Ca(2+) cycling costs, which makes it an ideal muscle model system offering prime conditions for studying the energetics of muscle contraction in vivo.

  14. Observational Study on the Occurrence of Muscle Spindles in Human Digastric and Mylohyoideus Muscles

    Directory of Open Access Journals (Sweden)

    Daniele Saverino

    2014-01-01

    Full Text Available Although the occurrence of muscle spindles (MS is quite high in most skeletal muscles of humans, few MS, or even absence, have been reported in digastric and mylohyoideus muscles. Even if this condition is generally accepted and quoted in many papers and books, observational studies are scarce and based on histological sections of a low number of specimens. The aim of the present study is to confirm previous data, assessing MS number in a sample of digastric and mylohyoideus muscles. We investigated 11 digastric and 6 mylohyoideus muscles from 13 donors. Muscle samples were embedded in paraffin wax, cross-sectioned in a rostrocaudal direction, and stained using haematoxylin-eosin. A mean of 5.1 ± 1.1 (range 3–7 MS was found in digastric muscles and mean of 0.5 ± 0.8 (range 0–2 in mylohyoideus muscles. A significant difference (P<0.001 was found with the control sample, confirming the correctness of the histological procedure. Our results support general belief that the absolute number of spindles is sparse in digastric and mylohyoideus muscles. External forces, such as food resistance during chewing or gravity, do not counteract jaw-opening muscles. It is conceivable that this condition gives them a limited proprioceptive importance and a reduced need for having specific receptors as MS.

  15. IMP metabolism in human skeletal muscle after exhaustive exercise

    DEFF Research Database (Denmark)

    Tullson, P. C.; Bangsbo, Jens; Hellsten, Ylva

    1995-01-01

    This study addressed whether AMP deaminase (AMPD)myosin binding occurs with deamination during intense exercise in humans and the extent of purine loss from muscle during the initial minutes of recovery. Male subjects performed cycle exercise (265 +/- 2 W for 4.39 +/- 0.04 min) to stimulate muscle...

  16. Regression of polyneural innervation in the human psoas muscle

    NARCIS (Netherlands)

    Gramsbergen, A; IjkemaPaassen, J; Nikkels, PGJ; HaddersAlgra, M

    1997-01-01

    During the early stages of mammalian ontogeny muscle fibres are innervated by more than one axon. This polyneural innervation is replaced by mononeural innervation in the course of development. The regression of polyneural innervation in the psoas muscle in the human is the topic of the present stud

  17. Reflex control of human jaw muscles.

    Science.gov (United States)

    Türker, Kemal S

    2002-01-01

    The aim of this review is to discuss what is known about the reflex control of the human masticatory system and to propose a method for standardized investigation. Literature regarding the current knowledge of activation of jaw muscles, receptors involved in the feedback control, and reflex pathways is discussed. The reflexes are discussed under the headings of the stimulation conditions. This was deliberately done to remind the reader that under each stimulation condition, several receptor systems are activated, and that it is not yet possible to stimulate only one afferent system in isolation in human mastication experiments. To achieve a method for uniform investigation, we need to set a method for stimulation of the afferent pathway under study with minimal simultaneous activation of other receptor systems. This stimulation should also be done in an efficient and reproducible way. To substantiate our conviction to standardize the stimulus type and parameters, we discuss the advantages and disadvantages of mechanical and electrical stimuli. For mechanical stimulus to be delivered in a reproducible way, the following precautions are suggested: The stimulus delivery system (often a probe attached to a vibrator) should be brought into secure contact with the area of stimulation. To minimize the slack between the probe, the area to be stimulated should be taken up by the application of pre-load, and the delivered force should be recorded in series. Electrical stimulus has advantages in that it can be delivered in a reproducible way, though its physiological relevance can be questioned. It is also necessary to standardize the method for recording and analyzing the responses of the motoneurons to the stimulation. For that, a new technique is introduced, and its advantages over the currently used methods are discussed. The new method can illustrate the synaptic potential that is induced in the motoneurons without the errors that are unavoidable in the current

  18. Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters

    Directory of Open Access Journals (Sweden)

    Andrea del Campo

    2016-01-01

    Full Text Available Sarcopenia is the loss of muscle mass accompanied by a decrease in muscle strength and resistance and is the main cause of disability among the elderly. Muscle loss begins long before there is any clear physical impact in the senior adult. Despite all this, the molecular mechanisms underlying muscle aging are far from being understood. Recent studies have identified that not only mitochondrial metabolic dysfunction but also mitochondrial dynamics and mitochondrial calcium uptake could be involved in the degeneration of skeletal muscle mass. Mitochondrial homeostasis influences muscle quality which, in turn, could play a triggering role in signaling of systemic aging. Thus, it has become apparent that mitochondrial status in muscle cells could be a driver of whole body physiology and organismal aging. In the present review, we discuss the existing evidence for the mitochondria related mechanisms underlying the appearance of muscle aging and sarcopenia in flies and mice.

  19. Maintenance of muscle mass and load-induced growth in Muscle RING Finger 1 null mice with age.

    Science.gov (United States)

    Hwee, Darren T; Baehr, Leslie M; Philp, Andrew; Baar, Keith; Bodine, Sue C

    2014-02-01

    Age-related loss of muscle mass occurs to varying degrees in all individuals and has a detrimental effect on morbidity and mortality. Muscle RING Finger 1 (MuRF1), a muscle-specific E3 ubiquitin ligase, is believed to mediate muscle atrophy through the ubiquitin proteasome system (UPS). Deletion of MuRF1 (KO) in mice attenuates the loss of muscle mass following denervation, disuse, and glucocorticoid treatment; however, its role in age-related muscle loss is unknown. In this study, skeletal muscle from male wild-type (WT) and MuRF1 KO mice was studied up to the age of 24 months. Muscle mass and fiber cross-sectional area decreased significantly with age in WT, but not in KO mice. In aged WT muscle, significant decreases in proteasome activities, especially 20S and 26S β5 (20-40% decrease), were measured and were associated with significant increases in the maladaptive endoplasmic reticulum (ER) stress marker, CHOP. Conversely, in aged MuRF1 KO mice, 20S or 26S β5 proteasome activity was maintained or decreased to a lesser extent than in WT mice, and no increase in CHOP expression was measured. Examination of the growth response of older (18 months) mice to functional overload revealed that old WT mice had significantly less growth relative to young mice (1.37- vs. 1.83-fold), whereas old MuRF1 KO mice had a normal growth response (1.74- vs. 1.90-fold). These data collectively suggest that with age, MuRF1 plays an important role in the control of skeletal muscle mass and growth capacity through the regulation of cellular stress. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

  20. Purinergic receptors expressed in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Bornø, A; Ploug, Thorkil; Bune, L T

    2012-01-01

    Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content...... of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age-matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy...... in immunolabelled transverse sections of muscle biopsies. The receptors P2Y(4), P2Y(11) and likely P2X(1) were present intracellularly or in the plasma membrane of muscle fibres and were thus selected for further detailed morphological analysis. P2X(1) receptors were expressed in intracellular vesicles...

  1. ATP economy of force maintenance in human tibialis anterior muscle

    DEFF Research Database (Denmark)

    Nakagawa, Yoshinao; Ratkevicius, Aivaras; Mizuno, Masao

    2005-01-01

    PURPOSE: The aim of this study was investigate ATP economy of force maintenance in the human tibialis anterior muscle during 60 s of anaerobic voluntary contraction at 50% of maximum voluntary contraction (MVC). METHODS: ATP turnover rate was evaluated using P magnetic resonance spectroscopy (P......-MRS). The total volume of ankle dorsiflexor muscles was assessed by H magnetic resonance imaging (MRI) (H-MRI), and the fiber type composition of the tibialis anterior muscle was evaluated using histochemical analysis of muscle biopsies. RESULTS: The tibialis anterior muscle occupied 59.7 +/- 0.6% (mean +/- SEM......) of the total ankle dorsiflexor muscle volume, which was 267 +/- 10 cm. Relative cross-sectional areas occupied by Type I, IIA, and IIB fibers in the tibialis anterior were 69.3 +/- 2.2, 27.4 +/- 2.76, and 3.2 +/- 1.0%, respectively. ATP economy of force maintenance did not change significantly during the 60-s...

  2. The intramuscular nerve supply of the human lateral cricoarytenoid muscle.

    Science.gov (United States)

    Sanders, I; Mu, L; Wu, B L; Biller, H F

    1993-09-01

    The lateral cricoarytenoid (LCA) muscle is one of the adductors of the vocal cords; however, some investigators believe that the lateral edge of the muscle may be involved in abduction. The possibility of functionally distinct compartments within the LCA was investigated by observing the pattern of the intramuscular nerve supply. This technique has previously clearly demonstrated neural compartments in the posterior cricoarytenoid, thyroarytenoid and cricothyroid muscles. Five adult human larynges were processed by the Sihler's stain which clears all soft tissue while counterstaining the nerves. The results of our study showed that the innervation pattern of the human LCA muscle is composed of a homogenous nerve plexus localized to the middle region of the muscle. This pattern correlates with the location of motor endplates described by prior investigators. The consistent neural pattern suggests that the LCA is composed of a single neuromuscular compartment.

  3. Group Ia afferents contribute to short-latency interlimb reflexes in the human biceps femoris muscle

    DEFF Research Database (Denmark)

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre

    2017-01-01

    and velocity of the iKnee rotations. Methods 11 seated participants (mean age: 25 ± 5 years) performed a voluntary isometric knee extension with the ipsilateral leg and contralateral knee flexion to 10% of maximum voluntary contraction (MVC). A mechanical actuator (MTS-Systems Corporation) imposed i...... amplitudes (4 vs. 8°) at the same 150°/s velocity (p’s > 0.08). Conclusion Because fast conducting group Ia muscle spindle afferents are sensitive to changes in muscle stretch velocity, while group II spindle afferents are sensitive to changes in amplitude (Grey et al., JPhysiol., 2001; Matthews, Trends...... Neurosci., 1991), group Ia velocity sensitive muscle spindle afferents likely contribute to the short-latency crossed spinal reflexes in the cBF muscle following iKnee joint rotations. This supports the findings for the short-latency crossed responses in the human soleus muscle (Stubbs & Mrachacz...

  4. Fiber type composition and maximum shortening velocity of muscles crossing the human shoulder.

    Science.gov (United States)

    Srinivasan, R C; Lungren, M P; Langenderfer, J E; Hughes, R E

    2007-03-01

    A study of the fiber type composition of fourteen muscles spanning the human glenohumeral joint was carried out with the purpose of determining the contribution of fiber types to overall muscle cross-sectional area (CSA) and to estimate the maximum shortening velocity (V(max)) of those muscles. Muscle biopsies were procured from 4 male cadavers (mean age 50) within 24 hr of death, snap frozen, mounted, and transversely sectioned (10 microm). Slides were stained for myofibrillar ATPase after alkaline preincubation. Photoimages were taken of defined areas (100 fibers) using the Bioquant system, and fiber type and CSA were measured from these images. Staining for mATPase produced three different fiber types: slow-oxidative (SO), fast-oxidative-glycolytic (FOG), and fast-glycolytic (FG). On average, the muscle fiber type composition ranged from 22 to 40% of FG, from 17 to 51% of FOG, and from 23 to 56% of SO. Twelve out of the 14 muscles had average SO proportions ranging from 35 to 50%. V(max) was calculated from the fiber type contribution relative to CSA and shortening velocity values taken from the literature. The maximum velocities of shortening presented here provide a physiological basis for the development of human shoulder musculoskeletal models suitable for predicting muscle forces for functionally relevant tasks encompassing conditions of muscle shortening and lengthening.

  5. Afferent contribution to locomotor muscle activity during unconstrained overground human walking: an analysis of triceps surae muscle fascicles

    DEFF Research Database (Denmark)

    Klint, Richard af; Cronin, Neil J.; Ishikawa, Masaki

    2010-01-01

    Plantar flexor series elasticity can be used to dissociate muscle fascicle and muscle tendon behaviour and, therefore, afferent feedback during human walking. We used electromyography (EMG) and high speed ultrasonography concomitantly to monitor muscle activity and muscle fascicle behaviour in ni...

  6. Decellularized Human Skeletal Muscle as Biologic Scaffold for Reconstructive Surgery

    Directory of Open Access Journals (Sweden)

    Andrea Porzionato

    2015-07-01

    Full Text Available Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin-EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation.

  7. Biology of muscle atrophy and of its recovery by FES in aging and mobility impairments: roots and by-products

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    Ugo Carraro

    2015-08-01

    Full Text Available There is something in our genome that dictates life expectancy and there is nothing that can be done to avoid this; indeed, there is not yet any record of a person who has cheated death. Our physical prowess can vacillate substantially in our lifetime according to our activity levels and nutritional status and we may fight aging, but we will inevitably lose. We have presented strong evidence that the atrophy which accompanies aging is to some extent caused by loss of innervation. We compared muscle biopsies of sedentary seniors to those of life long active seniors, and show that these groups indeed have a different distribution of muscle fiber diameter and fiber type. The senior sportsmen have many more slow fiber-type groupings than the sedentary people which provides strong evidence of denervation-reinnervation events in muscle fibers. It appears that activity maintains the motoneurons and the muscle fibers. Premature or accelerated aging of muscle may occur as the result of many chronic diseases. One extreme case is provided by irreversible damage of the Conus and Cauda Equina, a spinal cord injury (SCI sequela in which the human leg muscles may be completely and permanently disconnected from the nervous system with the almost complete disappearance of muscle fibers within 3-5 years from SCI. In cases of this extreme example of muscle degeneration, we have used 2D Muscle Color CT to gather data supporting the idea that electrical stimulation of denervated muscles can retain and even regain muscle. We show here that, if people are compliant, atrophy can be reversed. A further example of activity-related muscle adaptation is provided by the fact that mitochondrial distribution and density are significantly changed by functional electrical stimulation in horse muscle biopsies relative to those not receiving treatment. All together, the data indicate that FES is a good way to modify behaviors of muscle fibers by increasing the contraction load

  8. Biology of Muscle Atrophy and of its Recovery by FES in Aging and Mobility Impairments: Roots and By-Products.

    Science.gov (United States)

    Carraro, Ugo; Kern, Helmut; Gava, Paolo; Hofer, Christian; Loefler, Stefan; Gargiulo, Paolo; Mosole, Simone; Zampieri, Sandra; Gobbo, Valerio; Ravara, Barbara; Piccione, Francesco; Marcante, Andrea; Baba, Alfonc; Schils, Sheila; Pond, Amber; Gava, Francesco

    2015-08-24

    There is something in our genome that dictates life expectancy and there is nothing that can be done to avoid this; indeed, there is not yet any record of a person who has cheated death. Our physical prowess can vacillate substantially in our lifetime according to our activity levels and nutritional status and we may fight aging, but we will inevitably lose. We have presented strong evidence that the atrophy which accompanies aging is to some extent caused by loss of innervation. We compared muscle biopsies of sedentary seniors to those of life long active seniors, and show that these groups indeed have a different distribution of muscle fiber diameter and fiber type. The senior sportsmen have many more slow fiber-type groupings than the sedentary people which provides strong evidence of denervation-reinnervation events in muscle fibers. It appears that activity maintains the motoneurons and the muscle fibers. Premature or accelerated aging of muscle may occur as the result of many chronic diseases. One extreme case is provided by irreversible damage of the Conus and Cauda Equina, a spinal cord injury (SCI) sequela in which the human leg muscles may be completely and permanently disconnected from the nervous system with the almost complete disappearance of muscle fibers within 3-5 years from SCI. In cases of this extreme example of muscle degeneration, we have used 2D Muscle Color CT to gather data supporting the idea that electrical stimulation of denervated muscles can retain and even regain muscle. We show here that, if people are compliant, atrophy can be reversed. A further example of activity-related muscle adaptation is provided by the fact that mitochondrial distribution and density are significantly changed by functional electrical stimulation in horse muscle biopsies relative to those not receiving treatment. All together, the data indicate that FES is a good way to modify behaviors of muscle fibers by increasing the contraction load per day. Indeed, it

  9. Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles

    Directory of Open Access Journals (Sweden)

    Xiaoti Xu

    2015-09-01

    Full Text Available Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2–4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50–70 fiber-associated, or 1,000–5,000 FACS-enriched CD56+/CD29+ human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications.

  10. In vivo passive mechanical behaviour of muscle fascicles and tendons in human gastrocnemius muscle-tendon units.

    Science.gov (United States)

    Herbert, Robert D; Clarke, Jillian; Kwah, Li Khim; Diong, Joanna; Martin, Josh; Clarke, Elizabeth C; Bilston, Lynne E; Gandevia, Simon C

    2011-11-01

    Ultrasound imaging was used to measure the length of muscle fascicles in human gastrocnemius muscles while the muscle was passively lengthened and shortened by moving the ankle. In some subjects the muscle belly 'buckled' at short lengths. When the gastrocnemius muscle-tendon unit was passively lengthened from its shortest in vivo length by dorsiflexing the ankle, increases in muscle-tendon length were not initially accompanied by increases in muscle fascicle lengths (fascicle length remained constant), indicating muscle fascicles were slack at short muscle-tendon lengths. The muscle-tendon length at which slack is taken up differs among fascicles: some fascicles begin to lengthen at very short muscle-tendon lengths whereas other fascicles remain slack over a large range of muscle-tendon lengths. This suggests muscle fascicles are progressively 'recruited' and contribute sequentially to muscle-tendon stiffness during passive lengthening of the muscle-tendon unit. Even above their slack lengths muscle fascicles contribute only a small part (tendon length. The contribution of muscle fascicles to muscle-tendon length increases with muscle length. The novelty of this work is that it reveals a previously unrecognised phenomenon (buckling at short lengths), posits a new mechanism of passive mechanical properties of muscle (recruitment of muscle fascicles), and confirms with high-resolution measurements that the passive compliance of human gastrocnemius muscle-tendon units is due largely to the tendon. It would be interesting to investigate if adaptations of passive properties of muscles are associated with changes in the distribution of muscle lengths at which fascicles fall slack.

  11. Morphology of muscle attachment sites in the modern human hand does not reflect muscle architecture.

    Science.gov (United States)

    Williams-Hatala, E M; Hatala, K G; Hiles, S; Rabey, K N

    2016-06-23

    Muscle attachment sites (entheses) on dry bones are regularly used by paleontologists to infer soft tissue anatomy and to reconstruct behaviors of extinct organisms. This method is commonly applied to fossil hominin hand bones to assess their abilities to participate in Paleolithic stone tool behaviors. Little is known, however, about how or even whether muscle anatomy and activity regimes influence the morphologies of their entheses, especially in the hand. Using the opponens muscles from a sample of modern humans, we tested the hypothesis that aspects of hand muscle architecture that are known to be influenced by behavior correlate with the size and shape of their associated entheses. Results show no consistent relationships between these behaviorally-influenced aspects of muscle architecture and entheseal morphology. Consequently, it is likely premature to infer patterns of behavior, such as stone tool making in fossil hominins, from these same entheses.

  12. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Søren; Scheele, Camilla; Yfanti, Christina;

    2010-01-01

    of all four myomiRs (P training expression levels 14 days after ceasing the training programme. Components of major pathways involved in endurance adaptation such as MAPK and TGF-ß were predicted to be targeted by the myomiRs examined. Tested......, but their role in regulating human skeletal muscle adaptation remains unknown.......Muscle specific miRNAs, myomiRs, have been shown to control muscle development in vitro and are differentially expressed at rest in diabetic skeletal muscle. Therefore, we investigated the expression of these myomiRs, including miR-1, miR-133a, miR-133b and miR-206 in muscle biopsies from vastus...

  13. Effect of exercise on insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Mikines, K J; Galbo, Henrik

    1989-01-01

    The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization was perfo...... recovery of human skeletal muscle.......The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

  14. The impact of obesity on skeletal muscle strength and structure through adolescence to old age.

    Science.gov (United States)

    Tomlinson, D J; Erskine, R M; Morse, C I; Winwood, K; Onambélé-Pearson, Gladys

    2016-06-01

    Obesity is associated with functional limitations in muscle performance and increased likelihood of developing a functional disability such as mobility, strength, postural and dynamic balance limitations. The consensus is that obese individuals, regardless of age, have a greater absolute maximum muscle strength compared to non-obese persons, suggesting that increased adiposity acts as a chronic overload stimulus on the antigravity muscles (e.g., quadriceps and calf), thus increasing muscle size and strength. However, when maximum muscular strength is normalised to body mass, obese individuals appear weaker. This relative weakness may be caused by reduced mobility, neural adaptations and changes in muscle morphology. Discrepancies in the literature remain for maximal strength normalised to muscle mass (muscle quality) and can potentially be explained through accounting for the measurement protocol contributing to muscle strength capacity that need to be explored in more depth such as antagonist muscle co-activation, muscle architecture, a criterion valid measurement of muscle size and an accurate measurement of physical activity levels. Current evidence demonstrating the effect of obesity on muscle quality is limited. These factors not being recorded in some of the existing literature suggest a potential underestimation of muscle force either in terms of absolute force production or relative to muscle mass; thus the true effect of obesity upon skeletal muscle size, structure and function, including any interactions with ageing effects, remains to be elucidated.

  15. Intramuscular architecture of the autochthonous back muscles in humans.

    Science.gov (United States)

    Stark, Heiko; Fröber, Rosemarie; Schilling, Nadja

    2013-02-01

    Many training concepts take muscle properties such as contraction speed or muscle topography into account to achieve an optimal training outcome. Thus far, the internal architecture of muscles has largely been neglected, although it is well known that parameters such as pennation angles or the lengths of fascicles but also the proportions of fleshy and tendinous fascicle parts have a major impact on the contraction behaviour of a muscle. Here, we present the most detailed description of the intramuscular fascicle architecture of the human perivertebral muscles available so far. For this, one adult male cadaver was studied. Our general approach was to digitize the geometry of each fascicle of the muscles of back proper (Erector spinae) - the Spinalis thoracis, Iliocostalis lumborum, Longissimus thoracis and the Multifidus thoracis et lumborum - and of the deep muscles of the abdomen - Psoas minor, Psoas major and Quadratus lumborum - during a layerwise dissection. Architectural parameters such as fascicle angles to the sagittal and the frontal planes as well as fascicle lengths were determined for each fascicle, and are discussed regarding their consequences for the function of the muscle. For example, compared with the other dorsovertebral muscles, the Longissimus thoracis can produce greater shortening distances because of its relatively long fleshy portions, and it can store more elastic energy due to both its relatively long fleshy and tendinous fascicle portions. The Quadratus lumborum was outstanding because of its many architectural subunits defined by distinct attachment sites and fascicle lengths. The presented database will improve biomechanical models of the human trunk by allowing the incorporation of anisotropic muscle properties such as the fascicle direction into finite element models. This information will help to increase our understanding of the functionality of the human back musculature, and may thereby improve future training concepts.

  16. Shared muscle synergies in human walking and cycling.

    Science.gov (United States)

    Barroso, Filipe O; Torricelli, Diego; Moreno, Juan C; Taylor, Julian; Gomez-Soriano, Julio; Bravo-Esteban, Elisabeth; Piazza, Stefano; Santos, Cristina; Pons, José L

    2014-10-15

    The motor system may rely on a modular organization (muscle synergies activated in time) to execute different tasks. We investigated the common control features of walking and cycling in healthy humans from the perspective of muscle synergies. Three hypotheses were tested: 1) muscle synergies extracted from walking trials are similar to those extracted during cycling; 2) muscle synergies extracted from one of these motor tasks can be used to mathematically reconstruct the electromyographic (EMG) patterns of the other task; 3) muscle synergies of cycling can result from merging synergies of walking. A secondary objective was to identify the speed (and cadence) at which higher similarities emerged. EMG activity from eight muscles of the dominant leg was recorded in eight healthy subjects during walking and cycling at four matched cadences. A factorization technique [nonnegative matrix factorization (NNMF)] was applied to extract individual muscle synergy vectors and the respective activation coefficients behind the global muscular activity of each condition. Results corroborated hypotheses 2 and 3, showing that 1) four synergies from walking and cycling can successfully explain most of the EMG variability of cycling and walking, respectively, and 2) two of four synergies from walking appear to merge together to reconstruct one individual synergy of cycling, with best reconstruction values found for higher speeds. Direct comparison of the muscle synergy vectors of walking and the muscle synergy vectors of cycling (hypothesis 1) produced moderated values of similarity. This study provides supporting evidence for the hypothesis that cycling and walking share common neuromuscular mechanisms.

  17. Elevated skeletal muscle glucose transporter levels in exercise-trained middle-aged men.

    Science.gov (United States)

    Houmard, J A; Egan, P C; Neufer, P D; Friedman, J E; Wheeler, W S; Israel, R G; Dohm, G L

    1991-10-01

    Exercise training has been proposed to improve whole body insulin sensitivity through a postreceptor adaptation in skeletal muscle. This study examined if levels of the insulin-responsive muscle glucose transporter protein (GLUT-4) were associated with improved insulin sensitivity in trained vs. sedentary middle-aged individuals. Muscle GLUT-4 levels and oral glucose tolerance test (OGTT) responses were obtained in age-matched trained and sedentary men (n = 11). Plasma insulin levels during the OGTT were significantly lower (P less than 0.01) in the trained men, whereas no differences were seen in plasma glucose responses. GLUT-4 protein content was approximately twofold higher in the trained men (2.41 +/- 0.17 vs. 1.36 +/- 0.11 micrograms standard, P less than 0.001). OGTT responses and GLUT-4 levels were not altered 15-18 h after a standard exercise bout in six representative sedentary subjects. These data suggest that GLUT-4 levels are increased in conjunction with insulin sensitivity in chronically exercise-trained middle-aged men. This finding suggests a possible mechanism for the improved insulin sensitivity observed with exercise training in humans.

  18. Preliminary observations on the microarchitecture of the human abdominal muscles.

    Science.gov (United States)

    Woodley, Stephanie J; Duxson, Marilyn J; Mercer, Susan R

    2007-10-01

    Precise knowledge of muscle architecture and innervation patterns is essential for the development of accurate clinical and biomechanical models. Although the gross anatomy of the human abdominal muscles has been investigated, the finer details of their microanatomy are not well described. Fascicles were systematically sampled from each of the human abdominal muscles, and small fiber bundles from selected fascicles stained with acetylcholinesterase to determine the location of motor endplate bands, myomyonal junctions, and myotendinous junctions. Statistical analysis was used to ascertain the association between fascicular length and number of endplate bands. The number of endplate bands along a fascicle was variable between different portions of each muscle, but was strongly correlated with fascicular length (r = 0.814). In fascicles less than 50 millimeters (mm) in length, only a single endplate band was generally present, while multiple endplate bands (usually two or three) were found in fascicles longer than 50 mm. The presence of myomyonal junctions throughout the longer (>50 mm) fascicles verified that they were composed of short, intrafascicularly terminating fibers, while shorter fascicles comprised fibers spanning the entire fascicular length. This preliminary study provides evidence that multiple endplate bands are contained in some regions of the abdominal muscles, an arrangement that differs from most human appendicular muscles. It is not clear whether the variations in the described fine architectural features reflect regional differences in muscle function.

  19. Expiratory muscle loading increases intercostal muscle blood flow during leg exercise in healthy humans

    Science.gov (United States)

    Athanasopoulos, Dimitris; Louvaris, Zafeiris; Cherouveim, Evgenia; Andrianopoulos, Vasilis; Roussos, Charis; Zakynthinos, Spyros

    2010-01-01

    We investigated whether expiratory muscle loading induced by the application of expiratory flow limitation (EFL) during exercise in healthy subjects causes a reduction in quadriceps muscle blood flow in favor of the blood flow to the intercostal muscles. We hypothesized that, during exercise with EFL quadriceps muscle blood flow would be reduced, whereas intercostal muscle blood flow would be increased compared with exercise without EFL. We initially performed an incremental exercise test on eight healthy male subjects with a Starling resistor in the expiratory line limiting expiratory flow to ∼ 1 l/s to determine peak EFL exercise workload. On a different day, two constant-load exercise trials were performed in a balanced ordering sequence, during which subjects exercised with or without EFL at peak EFL exercise workload for 6 min. Intercostal (probe over the 7th intercostal space) and vastus lateralis muscle blood flow index (BFI) was calculated by near-infrared spectroscopy using indocyanine green, whereas cardiac output (CO) was measured by an impedance cardiography technique. At exercise termination, CO and stroke volume were not significantly different during exercise, with or without EFL (CO: 16.5 vs. 15.2 l/min, stroke volume: 104 vs. 107 ml/beat). Quadriceps muscle BFI during exercise with EFL (5.4 nM/s) was significantly (P = 0.043) lower compared with exercise without EFL (7.6 nM/s), whereas intercostal muscle BFI during exercise with EFL (3.5 nM/s) was significantly (P = 0.021) greater compared with that recorded during control exercise (0.4 nM/s). In conclusion, increased respiratory muscle loading during exercise in healthy humans causes an increase in blood flow to the intercostal muscles and a concomitant decrease in quadriceps muscle blood flow. PMID:20507965

  20. Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

    Science.gov (United States)

    Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

    2016-07-01

    Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies

  1. Green tea extract attenuates muscle loss and improves muscle function during disuse, but fails to improve muscle recovery following unloading in aged rats

    Science.gov (United States)

    Bennett, Brian T.; Wilson, Joseph C.; Sperringer, Justin; Mohamed, Junaith S.; Edens, Neile K.; Pereira, Suzette L.

    2014-01-01

    In this study we tested the hypothesis that green tea extract (GTE) would improve muscle recovery after reloading following disuse. Aged (32 mo) Fischer 344 Brown Norway rats were randomly assigned to receive either 14 days of hindlimb suspension (HLS) or 14 days of HLS followed by normal ambulatory function for 14 days (recovery). Additional animals served as cage controls. The rats were given GTE (50 mg/kg body wt) or water (vehicle) by gavage 7 days before and throughout the experimental periods. Compared with vehicle treatment, GTE significantly attenuated the loss of hindlimb plantaris muscle mass (−24.8% vs. −10.7%, P muscle function or mass compared with vehicle treatment, animals given green tea via gavage maintained the lower losses of muscle mass that were found during HLS (−25.2% vs. −16.0%, P muscle fiber cross-sectional area loss in both plantaris (−39.9% vs. −23.9%, P muscles after HLS. This green tea-induced difference was not transient but was maintained over the reloading period for plantaris (−45.6% vs. −21.5%, P muscle fiber cross-sectional area (−38.7% vs. −10.9%, P muscles during recovery from HLS compared with vehicle-treated muscles and decreased oxidative stress and abundance of the Bcl-2-associated X protein (Bax), yet this did not further improve muscle recovery in reloaded muscles. These data suggest that muscle recovery following disuse in aging is complex. Although satellite cell proliferation and differentiation are critical for muscle repair to occur, green tea-induced changes in satellite cell number is by itself insufficient to improve muscle recovery following a period of atrophy in old rats. PMID:25414242

  2. Intrinsic stiffness of extracellular matrix increases with age in skeletal muscles of mice.

    Science.gov (United States)

    Wood, Lauren K; Kayupov, Erdan; Gumucio, Jonathan P; Mendias, Christopher L; Claflin, Dennis R; Brooks, Susan V

    2014-08-15

    Advanced age is associated with increases in muscle passive stiffness, but the contributors to the changes remain unclear. Our purpose was to determine the relative contributions of muscle fibers and extracellular matrix (ECM) to muscle passive stiffness in both adult and old animals. Passive mechanical properties were determined for isolated individual muscle fibers and bundles of muscle fibers that included their associated ECM, obtained from tibialis anterior muscles of adult (8-12 mo old) and old (28-30 mo old) mice. Maximum tangent moduli of individual muscle fibers from adult and old muscles were not different at any sarcomere length tested. In contrast, the moduli of bundles of fibers from old mice was more than twofold greater than that of fiber bundles from adult muscles at sarcomere lengths >2.5 μm. Because ECM mechanical behavior is determined by the composition and arrangement of its molecular constituents, we also examined the effect of aging on ECM collagen characteristics. With aging, muscle ECM hydroxyproline content increased twofold and advanced glycation end-product protein adducts increased threefold, whereas collagen fibril orientation and total ECM area were not different between muscles from adult and old mice. Taken together, these findings indicate that the ECM of tibialis anterior muscles from old mice has a higher modulus than the ECM of adult muscles, likely driven by an accumulation of densely packed extensively crosslinked collagen.

  3. Molecular signatures of age-associated chronic degeneration of shoulder muscles.

    Science.gov (United States)

    Raz, Yotam; Henseler, Jan Ferdinand; Kolk, Arjen; Tatum, Zuotian; Groosjohan, Niels Kuipers; Verwey, Nisha E; Arindrarto, Wibowo; Kielbasa, Szymon M; Nagels, Jochem; 't Hoen, Peter A C; Nelissen, Rob G H H; Raz, Vered

    2016-02-23

    Chronic muscle diseases are highly prevalent in the elderly causing severe mobility limitations, pain and frailty. The intrinsic molecular mechanisms are poorly understood due to multifactorial causes, slow progression with age and variations between individuals. Understanding the underlying molecular mechanisms could lead to new treatment options which are currently limited. Shoulder complaints are highly common in the elderly, and therefore, muscles of the shoulder's rotator cuff could be considered as a model for chronic age-associated muscle degeneration. Diseased shoulder muscles were characterized by muscle atrophy and fatty infiltration compared with unaffected shoulder muscles. We confirmed fatty infiltration using histochemical analysis. Additionally, fibrosis and loss of contractile myosin expression were found in diseased muscles. Most cellular features, including proliferation rate, apoptosis and cell senescence, remained unchanged and genome-wide molecular signatures were predominantly similar between diseased and intact muscles. However, we found down-regulation of a small subset of muscle function genes, and up-regulation of extracellular region genes. Myogenesis was defected in muscle cell culture from diseased muscles but was restored by elevating MyoD levels. We suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration.

  4. Effects of Age, Sex, and Body Position on Orofacial Muscle Tone in Healthy Adults

    Science.gov (United States)

    Dietsch, Angela M.; Clark, Heather M.; Steiner, Jessica N.; Solomon, Nancy Pearl

    2015-01-01

    Purpose: Quantification of tissue stiffness may facilitate identification of abnormalities in orofacial muscle tone and thus contribute to differential diagnosis of dysarthria. Tissue stiffness is affected by muscle tone as well as age-related changes in muscle and connective tissue. Method: The Myoton-3 measured tissue stiffness in 40 healthy…

  5. Effects of Age, Sex, and Body Position on Orofacial Muscle Tone in Healthy Adults

    Science.gov (United States)

    Dietsch, Angela M.; Clark, Heather M.; Steiner, Jessica N.; Solomon, Nancy Pearl

    2015-01-01

    Purpose: Quantification of tissue stiffness may facilitate identification of abnormalities in orofacial muscle tone and thus contribute to differential diagnosis of dysarthria. Tissue stiffness is affected by muscle tone as well as age-related changes in muscle and connective tissue. Method: The Myoton-3 measured tissue stiffness in 40 healthy…

  6. Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass.

    Science.gov (United States)

    Râdegran, G; Blomstrand, E; Saltin, B

    1999-12-01

    The knee extensor exercise model was specifically developed to enable in vivo estimates of peak muscle blood flow and O(2) uptake in humans. The original finding, using thermodilution measurements to measure blood flow in relation to muscle mass [P. Andersen and B. Saltin. J. Physiol. (Lond.) 366: 233-249, 1985], was questioned, however, as the measurements were two- to threefold higher than those previously obtained with the (133)Xe clearance and the plethysmography technique. As thermodilution measurements have now been confirmed by other methods and independent research groups, we aimed to address the impact of muscle mass estimates on the peak values of muscle perfusion and O(2) uptake. In the present study, knee extensor volume was determined from multiple measurements with computer tomography along the full length of the muscle. In nine healthy humans, quadriceps muscle volume was 2.36 +/- 0.17 (range 1. 31-3.27) liters, corresponding to 2.48 +/- 0.18 (range 1.37-3.43) kg. Anthropometry overestimated the muscle volume by approximately 21-46%, depending on whether quadriceps muscle length was estimated from the patella to either the pubic bone, inguinal ligament, or spina iliaca anterior superior. One-legged, dynamic knee extensor exercise up to peak effort of 67 +/- 7 (range 55-100) W rendered peak values for leg blood flow (thermodilution) of 5.99 +/- 0.66 (range 4.15-9.52) l/min and leg O(2) uptake of 856 +/- 109 (range 590-1,521) ml/min. Muscle perfusion and O(2) uptake reached peak values of 246 +/- 24 (range 149-373) and 35.2 +/- 3.7 (range 22.6-59. 6) ml. min(-1). 100 g muscle(-1), respectively. These peak values are approximately 19-33% larger than those attained by applying anthropometric muscle mass estimates. In conclusion, the present findings emphasize that peak perfusion and O(2) uptake in human skeletal muscle may be up to approximately 30% higher than previous anthropometric-based estimates that use equivalent techniques for blood flow

  7. Regenerating human muscle fibres express GLUT3 protein

    DEFF Research Database (Denmark)

    Gaster, M; Beck-Nielsen, H; Schrøder, H D

    2002-01-01

    The presence of the GLUT3 glucose transporter protein in human muscle cells is a matter of debate. The present study was designed to establish whether GLUT3 is expressed in mature human skeletal muscle fibres and, if so, whether its expression changes under different conditions, such as metabolic...... stress (obesity, obese non-insulin-dependent diabetes mellitus), hypertrophy (training), de- and reinnervation (amyotrophic lateral sclerosis) or regeneration (polymyositis). We used an immunohistochemical approach to detect and localise GLUT3. GLUT3 immunoreactivity was not detectable in adult skeletal...... muscle fibres, nor did metabolic stress, training or de- and re-innervation induce GLUT3 expression, while a few GLUT3 expressing fibres were seen in some cases of polymyositis. In contrast, GLUT4 was expressed in all investigated muscle fibres. GLUT3 immunoreactivity was found in perineural...

  8. Glutamine attenuates post-traumatic glutathione depletion in human muscle.

    Science.gov (United States)

    Fläring, U B; Rooyackers, O E; Wernerman, J; Hammarqvist, F

    2003-03-01

    Glutathione is quantitatively the most important endogenous scavenger system. Glutathione depletion in skeletal muscle is pronounced following major trauma and sepsis in intensive care unit patients. Also, following elective surgery, glutathione depletion occurs in parallel with a progressive decline in muscle glutamine concentration. The present study was designed to test the hypothesis that glutamine supplementation may counteract glutathione depletion in a human trauma model. A homogeneous group of patients (n = 17) undergoing a standardized surgical procedure were prospectively randomly allocated to receive glutamine (0.56 g x day(-1) x kg(-1)) or placebo as part of isonitrogenous and isocaloric nutrition. Percutaneous muscle biopsies and blood samples were taken pre-operatively and at 24 and 72 h after surgery. The concentrations of muscle glutathione and related amino acids were determined in muscle tissue and plasma. In the control (unsupplemented) subjects, total muscle glutathione had decreased by 47+/-8% and 37+/-11% and reduced glutathione had decreased by 53+/-10% and 45+/-16% respectively at 24 and 72 h after surgery (P glutamine supplementation attenuates glutathione depletion in skeletal muscle in humans following standardized surgical trauma.

  9. Muscle Quality and Myosteatosis: Novel Associations With Mortality Risk: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

    Science.gov (United States)

    Reinders, Ilse; Murphy, Rachel A; Brouwer, Ingeborg A; Visser, Marjolein; Launer, Lenore; Siggeirsdottir, Kristin; Eiriksdottir, Gudny; Gudnason, Vilmundur; Jonsson, Palmi V; Lang, Thomas F; Harris, Tamara B

    2016-01-01

    Muscle composition may affect mortality risk, but prior studies have been limited to specific samples or less precise determination of muscle composition. We evaluated associations of thigh muscle composition, determined using computed tomography imaging, and knee extension strength with mortality risk among 4,824 participants aged 76.4 (standard deviation (SD), 5.5) years from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (2002-2006). Cox proportional hazards models were used to estimate hazard ratios. After 8.8 years of follow-up, there were 1,942 deaths. For men, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 11% and 22%. Each SD-increment increase in intermuscular adipose tissue and intramuscular adipose tissue was associated with higher mortality risk (hazard ratio (HR) = 1.13 (95% confidence interval (CI): 1.06, 1.22) and HR = 1.23 (95% CI: 1.15, 1.30), respectively). For women, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 12% and 19%. Greater intramuscular adipose tissue was associated with an 8% higher mortality risk (HR = 1.08, 95% CI: 1.01, 1.16). This study shows that muscle composition is associated with mortality risk. These results also show the importance of improving muscle strength and area and lowering muscle adipose tissue infiltration.

  10. Myosin Heavy Chain Composition of the Human Genioglossus Muscle

    Science.gov (United States)

    Daugherty, Megan; Luo, Qingwei; Sokoloff, Alan J.

    2012-01-01

    Background: The human tongue muscle genioglossus (GG) is active in speech, swallowing, respiration, and oral transport, behaviors encompassing a wide range of tongue shapes and movement speeds. Studies demonstrate substantial diversity in patterns of human GG motor unit activation, but whether this is accompanied by complex expression of muscle…

  11. Myosin Heavy Chain Composition of the Human Genioglossus Muscle

    Science.gov (United States)

    Daugherty, Megan; Luo, Qingwei; Sokoloff, Alan J.

    2012-01-01

    Background: The human tongue muscle genioglossus (GG) is active in speech, swallowing, respiration, and oral transport, behaviors encompassing a wide range of tongue shapes and movement speeds. Studies demonstrate substantial diversity in patterns of human GG motor unit activation, but whether this is accompanied by complex expression of muscle…

  12. Molecular and cellular mechanisms of muscle aging and sarcopenia and effects of electrical stimulation in seniors

    Directory of Open Access Journals (Sweden)

    Laura Barberi

    2015-08-01

    Full Text Available The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers, alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors.

  13. Molecular and Cellular Mechanisms of Muscle Aging and Sarcopenia and Effects of Electrical Stimulation in Seniors.

    Science.gov (United States)

    Barber, Laura; Scicchitano, Bianca Maria; Musaro, Antonio

    2015-08-24

    The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers), alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors..

  14. The challenges of human population ageing

    DEFF Research Database (Denmark)

    Sander, Miriam; Oxlund, Bjarke; Jespersen, Astrid;

    2015-01-01

    The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical...... of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20-21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create 'age-friendly' societies and promote 'ageing...

  15. Cyclooxygenase products sensitize muscle mechanoreceptors in humans with heart failure.

    Science.gov (United States)

    Middlekauff, Holly R; Chiu, Josephine; Hamilton, Michele A; Fonarow, Gregg C; Maclellan, W Robb; Hage, Antoine; Moriguchi, Jaime; Patel, Jignesh

    2008-04-01

    Prior work in animals and humans suggests that muscle mechanoreceptor control of sympathetic activation [muscle sympathetic nerve activity (MSNA)] during exercise in heart failure (HF) patients is heightened compared with that of healthy humans and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether cyclooxygenase products and/or endogenous adenosine, two metabolites of ischemic exercise, sensitize muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in HF patients. Indomethacin, which inhibits the production of prostaglandins, and saline control were infused in 12 HF patients. In a different protocol, aminophylline, which inhibits adenosine receptors, and saline control were infused in 12 different HF patients. MSNA was recorded (microneurography). During exercise following saline, MSNA increased in the first minute of exercise, consistent with baseline heightened mechanoreceptor sensitivity. MSNA continued to increase during 3 min of RHG, indicative that muscle mechanoreceptors are sensitized by ischemia metabolites. Indomethacin, but not aminophylline, markedly attenuated the increase in MSNA during the entire 3 min of low-level rhythmic exercise, consistent with the sensitization of muscle mechanoreceptors by cyclooxygenase products. Interestingly, even the early increase in MSNA was abolished by indomethacin infusion, indicative of the very early generation of cyclooxygenase products after the onset of exercise in HF patients. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in HF. Cyclooxygenase products, but not endogenous adenosine, play a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli, which also appears to be mediated by the early generation of cyclooxygenase products, resulting in exaggerated early increases in MSNA.

  16. Signaling pathways in failing human heart muscle cells.

    Science.gov (United States)

    Drexler, H; Hasenfuss, G; Holubarsch, C

    1997-07-01

    Experimental studies have delineated important signaling pathways in cardiomyocytes and their alterations in heart failure; however, there is now evidence that these observations are not necessarily applicable to human cardiac muscle cells. For example, angiotensin II (A II) does not exert positive inotropic effects in human ventricular muscle cells, in contrast to observation in rats. Thus, it is important to elucidate cardiac signaling pathways in humans in order to appreciate the functional role of neurohumoral or mechanical stimulation in human myocardium in health and disease. In the present article, we review signal pathways in the failing human heart based on studies in human cardiac tissues and in vivo physiological studies related to A II, nitric oxide, and β-adrenergic stimulation. (Trends Cardiovasc Med 1997; 7:151-160). © 1997, Elsevier Science Inc.

  17. Aging-related changes in the iron status of skeletal muscle.

    Science.gov (United States)

    DeRuisseau, Keith C; Park, Young-Min; DeRuisseau, Lara R; Cowley, Patrick M; Fazen, Christopher H; Doyle, Robert P

    2013-11-01

    The rise in non-heme iron (NHI) concentration observed in skeletal muscle of aging rodents is thought to contribute to the development of sarcopenia. The source of the NHI has not been identified, nor have the physiological ramifications of elevated iron status in aged muscle been directly examined. Therefore, we assessed plantaris NHI and heme iron (HI) levels in addition to expression of proteins involved in iron uptake (transferrin receptor-1; TfR1), storage (ferritin), export (ferroportin; FPN), and regulation (iron regulatory protein-1 (IRP1) and -2 (IRP2)) of male F344xBN F1 rats (n=10/group) of various ages (8, 18, 28, 32, and 36 months) to further understand iron regulation in aging muscle. In a separate experiment, iron chelator (pyridoxal isonicotinoyl hydrazone; PIH) or vehicle was administered to male F344xBN F1 rats (n=8/group) beginning at 30 months of age to assess the impact on plantaris muscle mass and function at ~36 months of age. Principle findings revealed the increased NHI concentration in old age was consistent with concentrating effects of muscle atrophy and reduction in HI levels, with no change in the total iron content of the muscle. The greatest increase in muscle iron content occurred during the period of animal growth and was associated with downregulation of TfR1 and IRP2 expression. Ferritin upregulation did not occur until senescence and the protein remained undetectable during the period of muscle iron content elevation. Lastly, administration of PIH did not significantly (p>0.05) impact NHI or measures of muscle atrophy or contractile function. In summary, this study confirms that the elevated NHI concentration in old age is largely due to the loss in muscle mass. The increased muscle iron content during aging does not appear to associate with cytosolic ferritin storage, but the functional consequences of elevated iron status in old age remains to be determined.

  18. A 3-Dimensional Atlas of Human Tongue Muscles

    Science.gov (United States)

    SANDERS, IRA; MU, LIANCAI

    2013-01-01

    The human tongue is one of the most important yet least understood structures of the body. One reason for the relative lack of research on the human tongue is its complex anatomy. This is a real barrier to investigators as there are few anatomical resources in the literature that show this complex anatomy clearly. As a result, the diagnosis and treatment of tongue disorders lags behind that for other structures of the head and neck. This report intended to fill this gap by displaying the tongue’s anatomy in multiple ways. The primary material used in this study was serial axial images of the male and female human tongue from the Visible Human (VH) Project of the National Library of Medicine. In addition, thick serial coronal sections of three human tongues were rendered translucent. The VH axial images were computer reconstructed into serial coronal sections and each tongue muscle was outlined. These outlines were used to construct a 3-dimensional computer model of the tongue that allows each muscle to be seen in its in vivo anatomical position. The thick coronal sections supplement the 3-D model by showing details of the complex interweaving of tongue muscles throughout the tongue. The graphics are perhaps the clearest guide to date to aid clinical or basic science investigators in identifying each tongue muscle in any part of the human tongue. PMID:23650264

  19. A three-dimensional atlas of human tongue muscles.

    Science.gov (United States)

    Sanders, Ira; Mu, Liancai

    2013-07-01

    The human tongue is one of the most important yet least understood structures of the body. One reason for the relative lack of research on the human tongue is its complex anatomy. This is a real barrier to investigators as there are few anatomical resources in the literature that show this complex anatomy clearly. As a result, the diagnosis and treatment of tongue disorders lags behind that for other structures of the head and neck. This report intended to fill this gap by displaying the tongue's anatomy in multiple ways. The primary material used in this study was serial axial images of the male and female human tongue from the Visible Human (VH) Project of the National Library of Medicine. In addition, thick serial coronal sections of three human tongues were rendered translucent. The VH axial images were computer reconstructed into serial coronal sections and each tongue muscle was outlined. These outlines were used to construct a three-dimensional (3D) computer model of the tongue that allows each muscle to be seen in its in vivo anatomical position. The thick coronal sections supplement the 3D model by showing details of the complex interweaving of tongue muscles throughout the tongue. The graphics are perhaps the clearest guide to date to aid clinical or basic science investigators in identifying each tongue muscle in any part of the human tongue.

  20. Dissociated small hand muscle atrophy in aging: the 'senile hand' is a split hand.

    NARCIS (Netherlands)

    Voermans, N.C.; Schelhaas, H.J.; Munneke, M.; Zwarts, M.J.

    2006-01-01

    The term 'split hand' refers to a pattern of dissociated atrophy of hand muscles and was first described in ALS. We hypothesize that this phenomenon also occurs in 'normal' aging. We investigated healthy subjects of different ages and found a progressive dissociation in atrophy of the hand muscles,

  1. A METHOD TO ASSESS THE DEVELOPMENT OF MUSCLE POWER IN PRETERMS AFTER TERM AGE

    NARCIS (Netherlands)

    DEGROOT, L; HOPKINS, B; TOUWEN, BCL

    1992-01-01

    The purpose of this paper is to report a detailed description of an instrument for evaluating the development of active and passive muscle power in preterms beyond term age. The instrument is constructed on a basis of age-specific items that assess these two components of muscle power and on the ass

  2. NMR imaging estimates of muscle volume and intramuscular fat infiltration in the thigh: variations with muscle, gender, and age.

    Science.gov (United States)

    Hogrel, Jean-Yves; Barnouin, Yoann; Azzabou, Noura; Butler-Browne, Gillian; Voit, Thomas; Moraux, Amélie; Leroux, Gaëlle; Behin, Anthony; McPhee, Jamie S; Carlier, Pierre G

    2015-06-01

    Muscle mass is particularly relevant to follow during aging, owing to its link with physical performance and autonomy. The objectives of this work were to assess muscle volume (MV) and intramuscular fat (IMF) for all the muscles of the thigh in a large population of young and elderly healthy individuals using magnetic resonance imaging (MRI) to test the effect of gender and age on MV and IMF and to determine the best representative slice for the estimation of MV and IMF. The study enrolled 105 healthy young (range 20-30 years) and older (range 70-80 years) subjects. MRI scans were acquired along the femur length using a three-dimension three-point Dixon proton density-weighted gradient echo sequence. MV and IMF were estimated from all the slices. The effects of age and gender on MV and IMF were assessed. Predictive equations for MV and IMF were established using a single slice at various femur levels for each muscle in order to reduce the analysis process. MV was decreased with aging in both genders, particularly in the quadriceps femoris. IMF was largely increased with aging in men and, to a lesser extent, in women. Percentages of MV decrease and IMF increase with aging varied according to the muscle. Predictive equations to predict MV and IMF from single slices are provided and were validated. This study is the first one to provide muscle volume and intramuscular fat infiltration in all the muscles of the thigh in a large population of young and elderly healthy subjects.

  3. Development of digastric muscles in human fetuses: a review and findings in the flexor digitorum superficialis muscle.

    Science.gov (United States)

    Rodríguez-Vázquez, José Francisco; Jin, Zhe Wu; Zhao, Peng; Murakami, Gen; Li, Xiang Wu; Jin, Yu

    2017-09-04

    The digastricus and omohyoideus muscles are digastric muscles with two muscle bellies. An insertion tendon of the posterior belly becomes an intermediate tendon in digastricus muscles, whereas a single band-like muscle in omohyoideus muscles may later be interrupted by an intermediate tendon, possibly due to muscle cell death caused by mechanical stress. In human fetuses, an intermediate tendon provides the temporal origins of the tensor veli palatini and tensor tympani muscles. Some reptiles, including snakes, carry multiple series of digastric-like axial muscles, in which each intersegmental septum is likely to become an intermediate tendon. These findings indicate that many pathways are involved in the development of digastric muscles. A review of these morphologies suggested that the flexor digitorum superficialis (FDS) muscle was a digastric muscle, although the intermediate tendon may not be visible in the surface view in adults. The present observations support the hypothesis that the proximal anlage at the elbow develops into a deep muscle slip to a limited finger, while the distal anlage at the wrist develops into the other slips. The findings suggest that, in the FDS muscle, the proximal and distal bellies of the embryonic digastric muscle fuse together to form a laminar structure, in which muscle slips accumulate from the palmar to the deep side of the forearm.

  4. Calprotectin is released from human skeletal muscle tissue during exercise

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Andersen, Kasper; Fischer, Christian

    2008-01-01

    Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained...... at time points 0, 3 and 6 h in these individuals and in resting controls. Affymetrix microarray analysis of gene expression changes in skeletal muscle biopsies identified a small set of genes changed by IL-6 infusion. RT-PCR validation confirmed that S100A8 and S100A9 mRNA were up-regulated 3-fold...... in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at approximately 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known...

  5. Robotic Powered Transfer Mechanism modeling on Human Muscle Structure

    Science.gov (United States)

    Saito, Yukio

    It is considered in engineering that one power source can operate one joint. However, support movement mechanism of living organism is multi joint movement mechanism. Considerably different from mechanical movement mechanism, two pairs of uni-articular muscles and a pair of bi-articular muscles are involved in it. In leg, movements observed in short run including leg idling, heel contact and toeing are operated by bi-articular muscles of the thigh showing strong legs to support body weight. Pursuit of versatility in welfare robot brings its comparison with conventional machinery or industrial robot to the fore. Request for safety and technology allowing elderly people to operate the robot is getting stronger in the society. The robot must be safe when it is used together with other welfare equipment and simpler system avoiding difficult operation has to be constructed. Appearance of recent care and assistance robot is getting similar to human arm in comparison with industrial robot. Being easily able to imagine from industrial robot, mid-heavyweight articulated robot to support 60-70kgf combined with large output motor and reduction gears is next to impossible to be installed in the bath room. This research indicated that upper limb arm and lower limb thigh of human and animals are holding coalitional muscles and movement of uni-artcular muscle and bi-articular muscle conjure the image of new actuators.

  6. Protein Intake and Muscle Health in Old Age: From Biological Plausibility to Clinical Evidence

    Directory of Open Access Journals (Sweden)

    Francesco Landi

    2016-05-01

    Full Text Available The provision of sufficient amounts of dietary proteins is central to muscle health as it ensures the supply of essential amino acids and stimulates protein synthesis. Older persons, in particular, are at high risk of insufficient protein ingestion. Furthermore, the current recommended dietary allowance for protein (0.8 g/kg/day might be inadequate for maintaining muscle health in older adults, probably as a consequence of “anabolic resistance” in aged muscle. Older individuals therefore need to ingest a greater quantity of protein to maintain muscle function. The quality of protein ingested is also essential to promoting muscle health. Given the role of leucine as the master dietary regulator of muscle protein turnover, the ingestion of protein sources enriched with this essential amino acid, or its metabolite β-hydroxy β-methylbutyrate, is thought to offer the greatest benefit in terms of preservation of muscle mass and function in old age.

  7. Telomere shortening in diaphragm and tibialis anterior muscles of aged mdx mice.

    Science.gov (United States)

    Lund, Troy C; Grange, Robert W; Lowe, Dawn A

    2007-09-01

    The progression of Duchenne muscular dystrophy (DMD) is, in part, due to satellite cell senescence driven by high replicative pressure as these muscle stem cells repeatedly divide and fuse to damaged muscle fibers. We hypothesize that telomere shortening in satellite cells underlies their senescence. To test this hypothesis, we evaluated the diaphragm and a leg muscle from dystrophic mice of various ages for telomere dynamics. We found 30% telomere shortening in tibialis anterior muscles from 600-day-old mdx mice relative to age-matched wildtype mice. We also found a more severe shortening of telomere length in diaphragm muscles of old mdx mice. In those muscles, telomeres were shortened by approximately 15% and 40% in 100- and 600-day-old mdx mice, respectively. These findings indicate that satellite cells undergo telomere erosion, which may contribute to the inability of these cells to perpetually repair DMD muscle.

  8. Duchenne Muscular Dystrophy Gene Expression in Normal and Diseased Human Muscle

    Science.gov (United States)

    Oronzi Scott, M.; Sylvester, J. E.; Heiman-Patterson, T.; Shi, Y.-J.; Fieles, W.; Stedman, H.; Burghes, A.; Ray, P.; Worton, R.; Fischbeck, K. H.

    1988-03-01

    A probe for the 5' end of the Duchenne muscular dystrophy (DMD) gene was used to study expression of the gene in normal human muscle, myogenic cell cultures, and muscle from patients with DMD. Expression was found in RNA from normal fetal muscle, adult cardiac and skeletal muscle, and cultured muscle after myoblast fusion. In DMD muscle, expression of this portion of the gene was also revealed by in situ RNA hybridization, particularly in regenerating muscle fibers.

  9. Training affects muscle phospholipid fatty acid composition in humans

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Wu, B J; Willer, Mette

    2001-01-01

    Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect...... on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk......, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 +/- 0.5% and 3.2 +/- 0.4% of total fatty acids, respectively) than the untrained leg (8.8 +/- 0.5% and 2.6 +/- 0.4%, P

  10. Exercise-induced metallothionein expression in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Pernille; Keller, Charlotte;

    2005-01-01

    in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

  11. New Predictive Index for Lumbar Paraspinal Muscle Degeneration Associated With Aging.

    Science.gov (United States)

    Takayama, Kazushi; Kita, Teruo; Nakamura, Hiroaki; Kanematsu, Fumiaki; Yasunami, Toshiya; Sakanaka, Hideki; Yamano, Yoshiki

    2016-01-01

    A cross-sectional imaging study of paraspinal muscle degeneration using a new index for easy evaluation. To examine the natural progression of age-related changes in the lumbar paraspinal muscles and to verify the validity of our new index for evaluating paraspinal muscle degenerationSUMMARY OF BACKGROUND DATA.: Measurement of paraspinal muscle morphology is an effective method for reflecting atrophy and fat infiltration, but it is complicated to perform. Therefore, we focused on the groove between lumbar paraspinal muscles as a simple index for evaluating paraspinal muscle degeneration. A total of 160 subjects aged 10 to 88 years (10 male and 10 female subjects in each decade) with lumbar lordosis of more than 20° were included. Body mass index (BMI) was calculated. Sagittal T2-weighted magnetic resonance imaging (MRI) was used to measure lumbar lordosis, while axial T2-weighted MRI was used to measure cross-sectional area (CSA) and fat infiltration rate of the paraspinal muscles at the intervertebral disc level from L1 to L5. To quantify the depth of the groove between the paraspinal muscles, our own image index (lumbar indentation value (LIV): equal to the length of the bulge of the muscle to the attachment of the spinous process), also was measured. We then determined the correlation between LIV and paraspinal muscle degeneration. There were no significant differences in BMI and lumbar lordosis between age groups. CSA of the paraspinal muscles tended to decrease with age, and fat infiltration rate increased with age. There was a negative correlation between CSA and fat infiltration rate at all levels (r = -0.474 to -0.634). LIV decreased significantly with age and strongly correlated with CSA at all levels (r = 0.709-0.789). Our new index is a simple and effective parameter for evaluating paraspinal muscle degeneration associated with aging. 4.

  12. Role of Exercise Therapy in Prevention of Decline in Aging Muscle Function: Glucocorticoid Myopathy and Unloading

    Directory of Open Access Journals (Sweden)

    Teet Seene

    2012-01-01

    Full Text Available Changes in skeletal muscle quantity and quality lead to disability in the aging population. Physiological changes in aging skeletal muscle are associated with a decline in mass, strength, and inability to maintain balance. Glucocorticoids, which are in wide exploitation in various clinical scenarios, lead to the loss of the myofibrillar apparatus, changes in the extracellular matrix, and a decrease in muscle strength and motor activity, particularly in the elderly. Exercise therapy has shown to be a useful tool for the prevention of different diseases, including glucocorticoid myopathy and muscle unloading in the elderly. The purpose of the paper is to discuss the possibilities of using exercise therapy in the prevention of glucocorticoid caused myopathy and unloading in the elderly and to describe relationships between the muscle contractile apparatus and the extracellular matrix in different types of aging muscles.

  13. Development of the stapedius muscle and pyramidal eminence in humans.

    Science.gov (United States)

    Rodríguez-Vázquez, J F

    2009-09-01

    The aim of the study was to systematize the key developmental phases of the stapedius muscle and the pyramidal eminence to clarify their formation, as well as to understand the variations and anomalies that can affect these structures. Sixty human embryos and fetuses between 38 days and 17 weeks of development were studied. The stapedius muscle is formed by two anlagen, one for the tendon, which derives from the internal segment of the interhyale, and another for the belly, located in the second pharyngeal arch medial to the facial nerve and near the interhyale but forming a completely independent anlage. In the interhyale, two segments were differentiated, these forming an angle; at the vertex, the belly of the stapedius muscle is attached. The internal segment is located from the attachment of the belly of the stapedius muscle to the anlage of the stapes, forming the anlage of the tendon of the stapedius muscle. The external segment completely disappears at the beginning of the fetal period. The pyramidal eminence is formed by an anlage independent of Reichert's cartilage, from the mesenchymal tissue of the tympanic cavity, which condenses around the belly of the stapedius muscle from 12 weeks of post-conception development. The length of the tendon of the stapedius muscle in adults varies, depending on the attachment site of the belly of the stapedius muscle in the interhyale, which would determine the length of the internal segment (anlage of the tendon) and consequently the tendon length. This variation depends on the greater or lesser persistence of the angulation observed during development, between the tendon and the belly of the stapedius muscle.

  14. Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons

    Science.gov (United States)

    Agarwal, Andrea B.; Feng, Cheng-Yuan; Altick, Amy L.; Quilici, David R.; Wen, Dan; Johnson, L. Alan; von Bartheld, Christopher S.

    2016-01-01

    Purpose To determine whether structural protein composition and expression of key regulatory genes are altered in strabismic human extraocular muscles. Methods Samples from strabismic horizontal extraocular muscles were obtained during strabismus surgery and compared with normal muscles from organ donors. We used proteomics, standard and customized PCR arrays, and microarrays to identify changes in major structural proteins and changes in gene expression. We focused on muscle and connective tissue and its control by enzymes, growth factors, and cytokines. Results Strabismic muscles showed downregulation of myosins, tropomyosins, troponins, and titin. Expression of collagens and regulators of collagen synthesis and degradation, the collagenase matrix metalloproteinase (MMP)2 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)1 and TIMP2, was upregulated, along with tumor necrosis factor (TNF), TNF receptors, and connective tissue growth factor (CTGF), as well as proteoglycans. Growth factors controlling extracellular matrix (ECM) were also upregulated. Among 410 signaling genes examined by PCR arrays, molecules with downregulation in the strabismic phenotype included GDNF, NRG1, and PAX7; CTGF, CXCR4, NPY1R, TNF, NTRK1, and NTRK2 were upregulated. Signaling molecules known to control extraocular muscle plasticity were predominantly expressed in the tendon rather than the muscle component. The two horizontal muscles, medial and lateral rectus, displayed similar changes in protein and gene expression, and no obvious effect of age. Conclusions Quantification of proteins and gene expression showed significant differences in the composition of extraocular muscles of strabismic patients with respect to important motor proteins, elements of the ECM, and connective tissue. Therefore, our study supports the emerging view that the molecular composition of strabismic muscles is substantially altered. PMID:27768799

  15. MRI-determined lumbar muscle morphometry in man and sheep: potential biomechanical implications for ovine model to human spine translation.

    Science.gov (United States)

    Valentin, Stephanie; Licka, Theresia F; Elliott, James

    2015-10-01

    The sheep is a commonly used animal model for human lumbar spine surgery, but only in vitro investigations comparing the human and ovine spine exist. Spinal musculature has previously not been compared between man and sheep. This additional knowledge could further indicate to what extent these species are biomechanically similar. Therefore, the purpose of the study was to investigate spinal muscle morphometric properties using magnetic resonance imaging (MRI) in different age groups of healthy human participants and sheep in vivo. Healthy human participants (n = 24) and sheep (n = 17) of different age groups underwent T1-weighted MRI of the lumbar spine. Regions of interest of the muscles erector spinae (ES), multifidus (M) and psoas (PS) were identified. The ratio of flexor to extensor volume, ratio of M to ES volume, and muscle fat relative to an area of intermuscular fat were calculated. Sheep M to ES ratio was significantly smaller than in the human participants (sheep 0.16 ± 0.02; human 0.37 ± 0.05; P sheep 0.43 ± 0.05; P = 0.06). Age did not influence any muscle ratio outcome. Sheep had significantly greater extensor muscle fat compared with the human participants (M left human 40.64%, sheep 53.81%; M right human 39.17%, sheep 51.33%; ES left human 40.86%, sheep 51.29%; ES right human 35.93%, sheep 44.38%; all median values; all P sheep 33.67%; PS right human 32.78%, sheep 30.09%; P sheep and human lumbar spine muscles may indicate dissimilar biomechanical and functional demands, which is an important consideration when translating to human surgical models.

  16. Why aging research? The moral imperative to retard human aging.

    Science.gov (United States)

    Farrelly, Colin

    2010-06-01

    The American philosopher John Rawls describes a fair system of social cooperation as one that is both rational and reasonable. Is it rational and reasonable for societies that (1) are vulnerable to diverse risks of morbidity (e.g., cancer, heart disease) and mortality and (2) are constrained by limited medical resources, to prioritize aging research? In this paper I make the case for answering "yes" on both accounts. Focusing on a plausible example of an applied gerontological intervention (i.e., an antiaging pharmaceutical), I argue that the goal of decelerating the rate of human aging would be a more effective strategy for extending the human health span than the current strategy of just tackling each specific disease of aging. Furthermore, the aspiration to retard human aging is also a reasonable aspiration, for the principle that underlies it (i.e., the duty to prevent harm) is one that no one could reasonably reject.

  17. Nutrition and muscle loss in humans during spaceflight

    Science.gov (United States)

    Stein, T. P.

    1999-01-01

    The protein loss in humans during spaceflight is partly due to a normal adaptive response to a decreased work load on the muscles involved in weight bearing. The process is mediated by changes in prostaglandin release, secondary to the decrease in tension on the affected muscles. On missions, where there is a high level of physical demands on the astronauts, there tends to be an energy deficit, which adds to the muscle protein loss and depletes the body fat reserves. While the adaptive response is a normal part of homeostasis, the additional protein loss from an energy deficit can, in the long run, have a negative effect on health and capability of humans to live and work in space and afterward return to Earth.

  18. Erythropoietin treatment enhances muscle mitochondrial capacity in humans

    DEFF Research Database (Denmark)

    Plenge, Ulla; Belhage, Bo; Guadalupe-Grau, Amelia;

    2012-01-01

    Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity...... in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis...... before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler...

  19. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...

  20. Age-related change in γH2AX of Drosophila muscle: its significance as a marker for muscle damage and longevity.

    Science.gov (United States)

    Jeon, Ho-Jun; Kim, Young-Shin; Park, Joung-Sun; Pyo, Jung-Hoon; Na, Hyun-Jin; Kim, In-Joo; Kim, Cheol-Min; Chung, Hae Young; Kim, Nam Deuk; Arking, Robert; Yoo, Mi-Ae

    2015-08-01

    Muscle aging is closely related to unhealthy late-life and organismal aging. Recently, the state of differentiated cells was shown to be critical to tissue homeostasis. Thus, understanding how fully differentiated muscle cells age is required for ensuring healthy aging. Adult Drosophila muscle is a useful model for exploring the aging process of fully differentiated cells. In this study, we investigated age-related changes of γH2AX, an indicator of DNA strand breaks, in adult Drosophila muscle to document whether its changes are correlated with muscle degeneration and lifespan. The results demonstrate that γH2AX accumulation increases in adult Drosophila thoracic and leg muscles with age. Analyses of short-, normal-, and long-lived strains indicate that the age-related increase of γH2AX is closely associated with the extent of muscle degeneration, cleaved caspase-3 and poly-ubiquitin aggregates, and longevity. Further analysis of muscle-specific knockdown of heterochromatin protein 1a revealed that the excessive γH2AX accumulation in thoracic and leg muscles induces accelerated degeneration and decreases longevity. These data suggest a strong correlation between age-related muscle damage and lifespan in Drosophila. Our findings indicate that γH2AX may be a reliable biomarker for assessing muscle aging in Drosophila.

  1. Ultrastructure of interstitial cells of Cajal in circular muscle of human small intestine

    DEFF Research Database (Denmark)

    Rumessen, J J; Mikkelsen, H B; Qvortrup, Klaus;

    1993-01-01

    Interstitial cells of Cajal (ICC) may be important regulatory cells in gut muscle layers. This study examined ICC within the circular muscle of human small intestine.......Interstitial cells of Cajal (ICC) may be important regulatory cells in gut muscle layers. This study examined ICC within the circular muscle of human small intestine....

  2. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

    Science.gov (United States)

    Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

    1999-01-01

    Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

  3. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

    Science.gov (United States)

    Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

    1999-01-01

    Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

  4. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle.

    Science.gov (United States)

    Dagdeviren, Sezin; Jung, Dae Young; Friedline, Randall H; Noh, Hye Lim; Kim, Jong Hun; Patel, Payal R; Tsitsilianos, Nicholas; Inashima, Kunikazu; Tran, Duy A; Hu, Xiaodi; Loubato, Marilia M; Craige, Siobhan M; Kwon, Jung Yeon; Lee, Ki Won; Kim, Jason K

    2017-02-01

    Altered energy balance and insulin resistance are important characteristics of aging. Skeletal muscle is a major site of glucose disposal, and the role of aging-associated inflammation in skeletal muscle insulin resistance remains unclear. To investigate, we examined glucose metabolism in 18-mo-old transgenic mice with muscle-specific overexpression of IL-10 (M(IL10)) and in wild-type mice during hyperinsulinemic-euglycemic clamping. Despite similar fat mass and energy balance, M(IL10) mice were protected from aging-associated insulin resistance with significant increases in glucose infusion rates, whole-body glucose turnover, and skeletal muscle glucose uptake (∼60%; P age-matched WT mice. This protective effect was associated with decreased muscle inflammation, but no changes in adipose tissue inflammation in aging M(IL10) mice. These results demonstrate the importance of skeletal muscle inflammation in aging-mediated insulin resistance, and our findings further implicate a potential therapeutic role of anti-inflammatory cytokine in the treatment of aging-mediated insulin resistance.-Dagdeviren, S., Jung, D. Y., Friedline, R. H., Noh, H. L., Kim, J. H., Patel, P. R., Tsitsilianos, N., Inashima, K., Tran, D. A., Hu, X., Loubato, M. M., Craige, S. M., Kwon, J. Y., Lee, K. W., Kim, J. K. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle. © FASEB.

  5. Effects of age and inactivity due to prolonged bed rest on atrophy of trunk muscles.

    Science.gov (United States)

    Ikezoe, Tome; Mori, Natsuko; Nakamura, Masatoshi; Ichihashi, Noriaki

    2012-01-01

    This study investigated the effects of age and inactivity due to being chronically bedridden on atrophy of trunk muscles. The subjects comprised 33 young women (young group) and 41 elderly women who resided in nursing homes or chronic care institutions. The elderly subjects were divided into two groups: independent elderly group who were able to perform activities of daily living involving walking independently (n = 28) and dependent elderly group who were chronically bedridden (n = 13). The thickness of the following six trunk muscles was measured by B-mode ultrasound: the rectus abdominis, external oblique, internal oblique, transversus abdominis, thoracic erector spinae (longissimus) and lumbar multifidus muscles. All muscles except for the transversus abdominis and lumbar multifidus muscles were significantly thinner in the independent elderly group compared with those in the young group. The thicknesses of all muscles in the dependent elderly group was significantly smaller than that in the young group, whereas there were no differences between the dependent elderly and independent elderly groups in the muscle thicknesses of the rectus abdominis and internal oblique muscles. In conclusion, our results suggest that: (1) age-related atrophy compared with young women was less in the deep antigravity trunk muscles than the superficial muscles in the independent elderly women; (2) atrophy associated with chronic bed rest was more marked in the antigravity muscles, such as the back and transversus abdominis.

  6. Effects of Age on Strength and Morphology of Toe Flexor Muscles.

    Science.gov (United States)

    Mickle, Karen J; Angin, Salih; Crofts, Gillian; Nester, Christopher J

    2016-12-01

    Study Design Descriptive, cross-sectional. Background Age-related muscle atrophy is common in lower-limb muscles. We therefore speculated that foot muscles may also diminish with age. However, there is a paucity of literature characterizing foot muscle strength and morphology, and any relationship between these 2, in older people. Objective To compare the strength and size of the toe flexor muscles of older adults relative to their younger counterparts. Methods Seventeen young adults with a normal foot type were matched by sex and body mass index to 17 older adults with a normal foot type, from an available sample of 41 younger (18 to 50 years of age) and 44 older (60 or more years of age) adults. Among the matched groups (n = 34), muscle thickness and cross-sectional area for 5 intrinsic and 2 extrinsic toe flexor muscles were obtained using ultrasound. Toe strength was assessed using a pressure platform. Differences in toe flexor strength and muscle size between the young and older matched groups were determined using analysis of covariance (controlling for height). Correlations between strength and size of the toe flexor muscles of the pooled group (n = 34) were also calculated. Results Toe strength and the thickness and cross-sectional area of most foot muscles were significantly reduced in the older adults (Pstrength values were strongly correlated with the size of the intrinsic toe flexor muscles. Conclusion The smaller foot muscles appear to be affected by sarcopenia in older adults. This could contribute to reduced toe flexion force production and may affect the ability of older people to walk safely. Interventions aimed at reversing foot muscle atrophy in older people require further investigation. J Orthop Sports Phys Ther 2016;46(12):1065-1070. Epub 29 Oct 2016. doi:10.2519/jospt.2016.6597.

  7. Ageing of the human hypothalamus.

    Science.gov (United States)

    Swaab, D F

    1995-01-01

    The various hypothalamic nuclei show very different patterns of change in ageing. These patterns are a basis for changes in biological rhythms, hormones, autonomous functions or behavior. The suprachiasmatic nucleus (SCN) coordinates circadian and circannual rhythms. A marked seasonal and circadian variation in the vasopressin (AVP) cell number of the SCN was observed in relation to the variation in photoperiod. During normal ageing, the circadian variation and number of AVP-expressing neurons in the SCN decreases. The sexually dimorphic nucleus (SDN), intermediate nucleus or INAH-1 is localized between the supraoptic and paraventricular nucleus (PVN). In adult men the SDN is twice as large as in adult women. In girls, the SDN shows a first period of decreasing cell numbers during prepubertal development, leading to sexual dimorphism. During ageing a decrease in cell number is found in both sexes. The cells of the supraoptic nucleus and PVN produce AVP or oxytocin and coexpress tyrosine hydroxylase. These nuclei are examples of neuron populations that seem to stay perfectly intact in ageing. Parvicellular corticotropin-releasing-hormone (CRH)-containing neurons are found throughout the PVN. CRH neurons in the PVN are activated in the course of ageing, as indicated by their increase in number and AVP coexpression. Part of the infundibular (or arcuate) nucleus, the subventricular nucleus, contains hypertrophic neurons in postmenopausal women. The hypertrophied neurons contain neurokinin-B (NKB), substance P and estrogen receptors and probably act on LHRH neurons as interneurons. The NKB neurons may also be involved in the initiation of menopausal flushes. The nucleus tuberalis lateralis might be involved in feeding behavior and metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. "Nutraceuticals" in relation to human skeletal muscle and exercise.

    Science.gov (United States)

    Deane, Colleen S; Wilkinson, Daniel J; Phillips, Bethan E; Smith, Kenneth; Etheridge, Timothy; Atherton, Philip J

    2017-04-01

    Skeletal muscles have a fundamental role in locomotion and whole body metabolism, with muscle mass and quality being linked to improved health and even lifespan. Optimizing nutrition in combination with exercise is considered an established, effective ergogenic practice for athletic performance. Importantly, exercise and nutritional approaches also remain arguably the most effective countermeasure for muscle dysfunction associated with aging and numerous clinical conditions, e.g., cancer cachexia, COPD, and organ failure, via engendering favorable adaptations such as increased muscle mass and oxidative capacity. Therefore, it is important to consider the effects of established and novel effectors of muscle mass, function, and metabolism in relation to nutrition and exercise. To address this gap, in this review, we detail existing evidence surrounding the efficacy of a nonexhaustive list of macronutrient, micronutrient, and "nutraceutical" compounds alone and in combination with exercise in relation to skeletal muscle mass, metabolism (protein and fuel), and exercise performance (i.e., strength and endurance capacity). It has long been established that macronutrients have specific roles and impact upon protein metabolism and exercise performance, (i.e., protein positively influences muscle mass and protein metabolism), whereas carbohydrate and fat intakes can influence fuel metabolism and exercise performance. Regarding novel nutraceuticals, we show that the following ones in particular may have effects in relation to 1) muscle mass/protein metabolism: leucine, hydroxyl β-methylbutyrate, creatine, vitamin-D, ursolic acid, and phosphatidic acid; and 2) exercise performance: (i.e., strength or endurance capacity): hydroxyl β-methylbutyrate, carnitine, creatine, nitrates, and β-alanine. Copyright © 2017 the American Physiological Society.

  9. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats.

    Science.gov (United States)

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E; Soto Hernandez, Jessica; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-11-24

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle.

  10. Electromyogram premotion silent period and tension development in human muscle.

    Science.gov (United States)

    Kawahats, K; Miyashita, M

    1983-11-01

    The EMG silent period has been observed frequently just before rapid movement from a slightly sustained contraction of the muscle. Our experiments were designed to show the relation between the tension developed in an intact human muscle and the occurrence of this silent period. Tension in the knee extensor was obtained from the floor reaction force of a living subject in a squatting position on the basis of a lever ratio-joint angle diagram obtained directly from measurements on an isolated knee extensor muscle of a human cadaver. The muscle tension was calculated under the condition that the floor reaction force in the squatting position passed through the anklebone, and decreased from 8.7 to 0.8 kN with an increase in the knee joint angle from 1.13 to 2.74 rad. When the center of pressure was not assumed, the increased knee extensor muscle torque with a decrease in the knee angle was estimated biomechanically from the free body diagram. Consistently, the EMG recordings confirmed an increased muscle activity with a reduction in the joint angle. The premotion silent period for the knee extensors and their antagonist with movement from the squatting position appeared to be limited to a knee joint angle of 2.44 to 3.07 rad, where the requirement for tension in those muscles was low. This silent period could be interpreted as an electromyographic transitional phase attributable to a switching mechanism in central nervous activity. The premotion silent period was most likely to appear prior to a swift, well coordinated movement.

  11. Age-related structural and functional changes of low back muscles.

    Science.gov (United States)

    Hiepe, Patrick; Gussew, Alexander; Rzanny, Reinhard; Kurz, Eduard; Anders, Christoph; Walther, Mario; Scholle, Hans-Christoph; Reichenbach, Jürgen R

    2015-05-01

    During aging declining maximum force capacity with more or less unchanged fatigability is observed with the underlying mechanisms still not fully understood. Therefore, we compared morphology and function of skeletal muscles between different age groups. Changes in high-energy phosphate turnover (PCr, Pi and pH) and muscle functional MRI (mfMRI) parameters, including proton transverse relaxation time (T2), diffusion (D) and vascular volume fraction (f), were investigated in moderately exercised low back muscles of young and late-middle-aged healthy subjects with (31)P-MR spectroscopy, T2- and diffusion-weighted MRI at 3T. In addition, T1-weighted MRI data were acquired to determine muscle cross-sectional areas (CSA) and to assess fat infiltration into muscle tissue. Except for pH, both age groups showed similar load-induced MR changes and rates of perceived exertion (RPE), which indicates comparable behavior of muscle activation at moderate loads. Changes of mfMRI parameters were significantly associated with RPE in both cohorts. Age-related differences were observed, with lower pH and higher Pi/ATP ratios as well as lower D and f values in the late-middle-aged subjects. These findings are ascribed to age-related changes of fiber type composition, fiber size and vascularity. Interestingly, post exercise f was negatively associated with fat infiltration with the latter being significantly higher in late-middle-aged subjects. CSA of low back muscles remained unchanged, while CSA of inner back muscle as well as mean T2 at rest were associated with maximum force capacity. Overall, applying the proposed MR approach provides evidence of age-related changes in several muscle tissue characteristics and gives new insights into the physiological processes that take place during aging.

  12. Physiological characterization of human muscle acetylcholine receptors from ALS patients

    Science.gov (United States)

    Palma, Eleonora; Inghilleri, Maurizio; Conti, Luca; Deflorio, Cristina; Frasca, Vittorio; Manteca, Alessia; Pichiorri, Floriana; Roseti, Cristina; Torchia, Gregorio; Limatola, Cristina; Grassi, Francesca; Miledi, Ricardo

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons leading to muscle paralysis. Research in transgenic mice suggests that the muscle actively contributes to the disease onset, but such studies are difficult to pursue in humans and in vitro models would represent a good starting point. In this work we show that tiny amounts of muscle from ALS or from control denervated muscle, obtained by needle biopsy, are amenable to functional characterization by two different technical approaches: “microtransplantation” of muscle membranes into Xenopus oocytes and culture of myogenic satellite cells. Acetylcholine (ACh)-evoked currents and unitary events were characterized in oocytes and multinucleated myotubes. We found that ALS acetylcholine receptors (AChRs) retain their native physiological characteristics, being activated by ACh and nicotine and blocked by α-bungarotoxin (α-BuTX), d-tubocurarine (dTC), and galantamine. The reversal potential of ACh-evoked currents and the unitary channel behavior were also typical of normal muscle AChRs. Interestingly, in oocytes injected with muscle membranes derived from ALS patients, the AChRs showed a significant decrease in ACh affinity, compared with denervated controls. Finally, riluzole, the only drug currently used against ALS, reduced, in a dose-dependent manner, the ACh-evoked currents, indicating that its action remains to be fully characterized. The two methods described here will be important tools for elucidating the role of muscle in ALS pathogenesis and for developing drugs to counter the effects of this disease. PMID:22128328

  13. The challenges of human population ageing

    DEFF Research Database (Denmark)

    Sander, Miriam; Oxlund, Bjarke; Jespersen, Astrid

    2015-01-01

    The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical...... of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20-21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create 'age-friendly' societies and promote 'ageing......-in-community'? what tools will effectively promote social engagement and prevent social detachment among older individuals? is there a risk that further extension of human lifespan would be a greater burden to the individual and to society than is warranted by the potential benefit of longer life?...

  14. Re-evaluation of sarcolemma injury and muscle swelling in human skeletal muscles after eccentric exercise.

    Science.gov (United States)

    Yu, Ji-Guo; Liu, Jing-Xia; Carlsson, Lena; Thornell, Lars-Eric; Stål, Per S

    2013-01-01

    The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2-3 days and 7-8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7-8 days than at 2-3 days post exercise (pexercise (lower in 5 of the 6 subjects at 7-8 days than at 2-3 days; pexercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS.

  15. Obesity accelerates epigenetic aging of human liver

    OpenAIRE

    Horvath, S; Erhart, W.; Brosch, M; Ammerpohl, O.; von Schonfels, W.; Ahrens, M.; Heits, N.; Bell, J.T.; Tsai, P.-C.; Spector, T D; Deloukas, P.; Siebert, R.; Sipos, B.; Becker, T.; Rocken, C.

    2014-01-01

    Because obese people are at an increased risk of many age-related diseases, it is a plausible hypothesis that obesity increases the biological age of some tissues and cell types. However, it has been difficult to detect such an accelerated aging effect because it is unclear how to measure tissue age. Here we use a recently developed biomarker of aging (known as “epigenetic clock”) to study the relationship between epigenetic age and obesity in several human tissues. We report an unexpectedly ...

  16. Enhanced Muscle Afferent Signals during Motor Learning in Humans.

    Science.gov (United States)

    Dimitriou, Michael

    2016-04-25

    Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a function of adaptation state. Specifically, spindle control was independent of concurrent muscle activity but was specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80 ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "γ" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning.

  17. Multi-frequency bioimpedance in human muscle assessment

    DEFF Research Database (Denmark)

    Bartels, Else Marie; Sørensen, Emma Rudbæk; Harrison, Adrian Paul

    2015-01-01

    Bioimpedance analysis (BIA) is a well-known and tested method for body mass and muscular health assessment. Multi-frequency BIA (mfBIA) equipment now makes it possible to assess a particular muscle as a whole, as well as looking at a muscle at the fiber level. The aim of this study was to test...... healthy human control subjects and three selected cases were examined to demonstrate the extent to which this method may be used clinically, and in relation to training in sport. The electrode setup is shown to affect the mfBIA parameters recorded. Our recommendation is the use of noble metal electrodes...

  18. Erythropoietin treatment enhances mitochondrial function in human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Ulla ePlenge

    2012-03-01

    Full Text Available Abstract Erythropoietin (Epo treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over eight weeks with oral iron (100 mg supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92±5 to 113±7 pmol.sec-1.mg-1 and ETS (107±4 to 143±14 pmol.sec-1.mg-1, P<0.05, demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

  19. The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity.

    Science.gov (United States)

    Love, Lorenzo K; LeBlanc, Paul J; Inglis, J Greig; Bradley, Nicolette S; Choptiany, Jon; Heigenhauser, George J F; Peters, Sandra J

    2011-08-01

    Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r(2) = 0.399, P = 0.001) and PDP1 protein expression (r(2) = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α (r(2) = 0.310, P = 0.002) and PDK2 protein (r(2) = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼ 18% of the variance in PDP activity (r(2) = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼ 38% of the variance in PDP activity (r(2) = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity).

  20. Stuck in gear: age-related loss of variable gearing in skeletal muscle.

    Science.gov (United States)

    Holt, Natalie C; Danos, Nicole; Roberts, Thomas J; Azizi, Emanuel

    2016-04-01

    Skeletal muscles power a broad diversity of animal movements, despite only being able to produce high forces over a limited range of velocities. Pennate muscles use a range of gear ratios, the ratio of muscle shortening velocity to fiber shortening velocity, to partially circumvent these force-velocity constraints. Muscles operate with a high gear ratio at low forces; fibers rotate to greater angles of pennation, enhancing velocity but compromising force. At higher forces, muscles operate with a lower gear ratio; fibers rotate little so limiting muscle shortening velocity, but helping to preserve force. This ability to shift gears is thought to be due to the interplay of contractile force and connective tissue constraints. In order to test this hypothesis, gear ratios were determined in the medial gastrocnemius muscles of both healthy young rats, and old rats where the interaction between contractile and connective tissue properties was assumed to be disrupted. Muscle fiber and aponeurosis stiffness increased with age (Pmuscles, indicating that variable gearing is lost in old muscle. These findings support the hypothesis that variable gearing results from the interaction between contractile and connective tissues and suggest novel explanations for the decline in muscle performance with age.

  1. A comparative study of beef quality after ageing longissimus muscle using a dry ageing bag, traditional dry ageing or vacuum package ageing.

    Science.gov (United States)

    Li, Xin; Babol, Jakub; Bredie, Wender L P; Nielsen, Belinda; Tománková, Jana; Lundström, Kerstin

    2014-08-01

    The objective of this study was to investigate beef quality of longissimus muscle after ageing in dry ageing bags, traditional dry ageing or vacuum for 8 or 19 days. Lower ageing weight loss, odour score and microbial growth were found in meat aged in dry ageing bags than after traditional dry ageing. The sensory panel detected no differences for most of the sensory attributes between samples using the two dry ageing methods, except for the odour of the cutting surface. The dry-aged steaks had more umami and butter fried meat taste compared with vacuum-aged steaks. Ageing time affected most of the sensory traits in this study, which improved as ageing time increased from 8 to 19 days. In a consumer test, meat aged for 21 days in dry ageing bags was preferred than the samples aged in vacuum. This may be due to the higher tenderness and juiciness obtained during storage in dry ageing bags than meat aged in vacuum.

  2. Age-Related Differences in Gait Kinematics, Kinetics, and Muscle Function: A Principal Component Analysis.

    Science.gov (United States)

    Schloemer, Sarah A; Thompson, Julie A; Silder, Amy; Thelen, Darryl G; Siston, Robert A

    2017-03-01

    Age-related increased hip extensor recruitment during gait is a proposed compensation strategy for reduced ankle power generation and may indicate a distal-to-proximal shift in muscle function with age. Extending beyond joint level analyses, identifying age-related changes at the muscle level could capture more closely the underlying mechanisms responsible for movement. The purpose of this study was to characterize and compare muscle forces and induced accelerations during gait in healthy older adults with those of young adults. Simulations of one gait cycle for ten older (73.9 ± 5.3 years) and six young (21.0 ± 2.1 years) adults walking at their self-selected speed were analyzed. Muscle force and induced acceleration waveforms, along with kinematic, kinetic, and muscle activation waveforms, were compared between age-groups using principal component analysis. Simulations of healthy older adults had greater gluteus maximus force and vertical support contribution, but smaller iliacus force, psoas force, and psoas vertical support contribution. There were no age-group differences in distal muscle force, contribution, or ankle torque magnitudes. Later peak dorsiflexion and peak ankle angular velocity in older adults may have contributed to their greater ankle power absorption during stance. These findings reveal the complex interplay between age-related changes in neuromuscular control, kinematics, and muscle function during gait.

  3. Elastin aging and lipid oxidation products in human aorta

    Directory of Open Access Journals (Sweden)

    Kamelija Zarkovic

    2015-04-01

    Full Text Available Vascular aging is associated with structural and functional modifications of the arteries, and by an increase in arterial wall thickening in the intima and the media, mainly resulting from structural modifications of the extracellular matrix (ECM components. Among the factors known to accumulate with aging, advanced lipid peroxidation end products (ALEs are a hallmark of oxidative stress-associated diseases such as atherosclerosis. Aldehydes generated from the peroxidation of polyunsaturated fatty acids (PUFA, (4-hydroxynonenal, malondialdehyde, acrolein, form adducts on cellular proteins, leading to a progressive protein dysfunction with consequences in the pathophysiology of vascular aging. The contribution of these aldehydes to ECM modification is not known. This study was carried out to investigate whether aldehyde-adducts are detected in the intima and media in human aorta, whether their level is increased in vascular aging, and whether elastin fibers are a target of aldehyde-adduct formation. Immunohistological and confocal immunofluorescence studies indicate that 4-HNE-histidine-adducts accumulate in an age-related manner in the intima, media and adventitia layers of human aortas, and are mainly expressed in smooth muscle cells. In contrast, even if the structure of elastin fiber is strongly altered in the aged vessels, our results show that elastin is not or very poorly modified by 4-HNE. These data indicate a complex role for lipid peroxidation and in particular for 4-HNE in elastin homeostasis, in the vascular wall remodeling during aging and atherosclerosis development.

  4. Intermuscular force transmission between human plantarflexor muscles in vivo

    DEFF Research Database (Denmark)

    Bojsen-Møller, Jens; Bojsen-Møller, Jens; Schwartz, Sidse;

    2010-01-01

    of the present study was to investigate if intermuscular force transmission occurs within and between human plantarflexor muscles in vivo. Seven subjects performed four types of either active contractile tasks or passive joint manipulations: passive knee extension, voluntary isometric plantarflexion, voluntary...... isometric hallux flexion, passive hallux extension, and selective percutaneous stimulation of the gastrocnemius medialis (MG). In each experiment plantar- and hallux flexion force and corresponding EMG activity were sampled. During all tasks ultrasonography was applied at proximal and distal sites to assess...... task-induced tissue displacement (which is assumed to represent loading) for the plantarflexor muscles [MG, soleus (SOL), and flexor hallucis longus (FHL)]. Selective MG stimulation and passive knee extension resulted in displacement of both the MG and SOL muscles. Minimal displacement of the triceps...

  5. MuscleBuilder:A Modeling Tool for Human Anatomy

    Institute of Scientific and Technical Information of China (English)

    Amaury Aubel; Daniel Thalmann

    2004-01-01

    A traditional multi-layered approach is adopted to human body modeling and deformation. The model is split into three general anatomical structures: the skeleton, musculature and skin. It is shown that each of these layers is modeled and deformed by using fast, procedural, ad-hoc methods that can painlessly be reimplemented. The modeling approach is generic enough to handle muscles of varying shape, size and characteristics and does not break in extreme skeleton poses. It is also described that the integrated MuscleBuilder system whose main features are: i) easy and quick creation of muscle deformation models; ii) automatic deformation of an overlying skin. It is shown that visually realistic results can be obtained at interactive frame rates with very little input from the designer.

  6. Enhancement of Skeletal Muscle in Aged Rats Following High-Intensity Stretch-Shortening Contraction Training.

    Science.gov (United States)

    Rader, Erik P; Naimo, Marshall A; Layner, Kayla N; Triscuit, Alyssa M; Chetlin, Robert D; Ensey, James; Baker, Brent A

    2016-08-03

    Exercise is the most accessible, efficacious, and multifactorial intervention to improve health and treat chronic disease. High-intensity resistance exercise, in particular, also maximizes skeletal muscle size and strength-outcomes crucial at advanced age. However, such training is capable of inducing muscle maladaptation when misapplied at old age. Therefore, characterization of parameters (e.g., mode and frequency) that foster adaptation is an active research area. To address this issue, we utilized a rodent model that allowed training at maximal intensity in terms of muscle activation and tested the hypothesis that muscles of old rats adapt to stretch-shortening contraction (SSC) training, provided the training frequency is sufficiently low. At termination of training, normalized muscle mass (i.e., muscle mass divided by tibia length) and muscle quality (isometric force divided by normalized muscle mass) were determined. For young rats, normalized muscle mass increased by ∼20% regardless of training frequency. No difference was observed for muscle quality values after 2 days versus 3 days per week training (0.65 ± 0.09 N/mg/mm vs. 0.59 ± 0.05 N/mg/mm, respectively). For old rats following 3 days per week training, normalized muscle mass was unaltered and muscle quality was 30% lower than young levels. Following 2 days per week training at old age, normalized muscle mass increased by 17% and muscle quality was restored to young levels. To investigate this enhanced response, oxidative stress was assessed by lipid peroxidation quantification. For young rats, lipid peroxidation levels were unaltered by training. With aging, baseline levels of lipid peroxidation increased by 1.5-fold. For old rats, only 2 days per week training decreased lipid peroxidation to levels indistinguishable from young values. These results imply that, appropriately scheduled high-intensity SSC training at old age is capable of restoring muscle to a younger phenotype in terms

  7. EFFECT OF HEAT PRECONDITIONING BY MICROWAVE HYPERTHERMIA ON HUMAN SKELETAL MUSCLE AFTER ECCENTRIC EXERCISE

    Directory of Open Access Journals (Sweden)

    Norio Saga

    2008-03-01

    Full Text Available The purpose of this study was to clarify whether heat preconditioning results in less eccentric exercise-induced muscle damage and muscle soreness, and whether the repeated bout effect is enhanced by heat preconditioning prior to eccentric exercise. Nine untrained male volunteers aged 23 ± 3 years participated in this study. Heat preconditioning included treatment with a microwave hyperthermia unit (150 W, 20 min that was randomly applied to one of the subject's arms (MW; the other arm was used as a control (CON. One day after heat preconditioning, the subjects performed 24 maximal isokinetic eccentric contractions of the elbow flexors at 30°·s-1 (ECC1. One week after ECC1, the subjects repeated the procedure (ECC2. After each bout of exercise, maximal voluntary contraction (MVC, range of motion (ROM of the elbow joint, upper arm circumference, blood creatine kinase (CK activity and muscle soreness were measured. The subjects experienced both conditions at an interval of 3 weeks. MVC and ROM in the MW were significantly higher than those in the CON (p < 0.05 for ECC1; however, the heat preconditioning had no significant effect on upper arm circumference, blood CK activity, or muscle soreness following ECC1 and ECC2. Heat preconditioning may protect human skeletal muscle from eccentric exercise-induced muscle damage after a single bout of eccentric exercise but does not appear to promote the repeated bout effect after a second bout of eccentric exercise

  8. Differences in Age-Related Alterations in Muscle Contraction Properties in Rat Tongue and Hindlimb

    Science.gov (United States)

    Connor, Nadine P.; Ota, Fumikazu; Nagai, Hiromi; Russell, John A.; Leverson, Glen

    2008-01-01

    Purpose: Because of differences in muscle architecture and biomechanics, the purpose of this study was to determine whether muscle contractile properties of rat hindlimb and tongue were differentially affected by aging. Method: Deep peroneal and hypoglossal nerves were stimulated in 6 young and 7 old Fischer 344-Brown Norway rats to allow…

  9. Differences in Age-Related Alterations in Muscle Contraction Properties in Rat Tongue and Hindlimb

    Science.gov (United States)

    Connor, Nadine P.; Ota, Fumikazu; Nagai, Hiromi; Russell, John A.; Leverson, Glen

    2008-01-01

    Purpose: Because of differences in muscle architecture and biomechanics, the purpose of this study was to determine whether muscle contractile properties of rat hindlimb and tongue were differentially affected by aging. Method: Deep peroneal and hypoglossal nerves were stimulated in 6 young and 7 old Fischer 344-Brown Norway rats to allow…

  10. The Changes of Muscle Strength and Functional Activities During Aging in Male and Female Populations

    Directory of Open Access Journals (Sweden)

    Shih-Jung Cheng

    2014-12-01

    Conclusion: We noted that the muscle strength and functional activities were decreased earlier in female than male individuals. The decrease of functional activities during the aging process seems to be earlier than the decrease of muscle strength. It is important to implement functional activities training in addition to strengthening exercise to maintain functional levels of the geriatric population.

  11. Altered microRNA expression in bovine skeletal muscle with age

    Science.gov (United States)

    Age dependent decline in skeletal muscle function leads to several inherited and acquired muscular disorders in elderly individuals. The levels of microRNAs (miRNAs) could be altered during muscle maintenance and repair. Therefore, we performed a comprehensive investigation for miRNAs from 5 differe...

  12. From chaos to split-ups--SHG microscopy reveals a specific remodelling mechanism in ageing dystrophic muscle.

    Science.gov (United States)

    Buttgereit, Andreas; Weber, Cornelia; Garbe, Christoph S; Friedrich, Oliver

    2013-02-01

    Duchenne muscular dystrophy (DMD) is a common inherited muscle disease showing chronic inflammation and progressive muscle weakness. Absent dystrophin renders sarcolemma more Ca(2+) -permeable, disturbs signalling and triggers inflammation. Sustained degeneration/regeneration cycles render muscle cytoarchitecture susceptible to remodelling. Quantitative morphometry was introduced in living cells using second-harmonic generation (SHG) microscopy of myosin. As the time course of cellular remodelling is not known, we used SHG microscopy in mdx muscle fibres over a wide age range for three-dimensional (3D) rendering and detection of verniers and cosine angle sums (CASs). Wild-type (wt) and transgenic mini-dystrophin mice (MinD) were also studied. Vernier densities (VDs) declined in wt and MinD fibres until adulthood, while in mdx fibres, VDs remained significantly elevated during the life span. CAS values were close to unity in adult wt and MinD fibres, in agreement with tight regular myofibril orientation, while always smaller in mdx fibres. Using SHG 3D morphometry, we identified two types of altered ultrastructure: branched fibres and a novel, previously undetected 'chaotic' fibre type, both of which can be classified by distinct CAS and VD combinations. We present a novel model of tissue remodelling in dystrophic progression with age that involves the transition from normal to chaotic to branched fibres. Our model predicts a ~50% contribution of altered cytoarchitecture to progressive force loss with age. We also provide an improved automated image algorithm that is suitable for future ageing studies in human myopathies.

  13. Isokinetic and Isometric Muscle Strength in a Healthy Population – with Special Reference to Age and Gender

    DEFF Research Database (Denmark)

    Danneskiold-Samsøe, B; Bartels, E M; Bülow, P M

    2009-01-01

    was subgrouped according to age and gender. Isometric and isokinetic muscle strength was measured in each subject across the main joints in the body. A statistical model was developed that encompassed the three main muscle groups: upper limbs, trunk and lower limbs. Results: Muscle strength in healthy men...... decreases in a linear fashion from the age of 25 years down to between 54% and 89% at the age of 75 years, and seems not highly dependent on any other parameter than age. For women, the muscle strength is dependent on weight and is only related to age from around 40 years of age. The decrease in muscle...

  14. Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Gnaiger, Erich; Calbet, Jose A L

    2011-01-01

    Across a wide range of species and body mass a close matching exists between maximal conductive oxygen delivery and mitochondrial respiratory rate. In this study we investigated in humans how closely in-vivo maximal oxygen consumption (VO(2) max) is matched to state 3 muscle mitochondrial...... respiration. High resolution respirometry was used to quantify mitochondrial respiration from the biopsies of arm and leg muscles while in-vivo arm and leg VO(2) were determined by the Fick method during leg cycling and arm cranking. We hypothesized that muscle mitochondrial respiratory rate exceeds...... that of systemic oxygen delivery. The state 3 mitochondrial respiration of the deltoid muscle (4.3±0.4 mmol o(2)kg(-1) min(-1)) was similar to the in-vivo VO(2) during maximal arm cranking (4.7±0.5 mmol O(2) kg(-1) min(-1)) with 6 kg muscle. In contrast, the mitochondrial state 3 of the quadriceps was 6.9±0.5 mmol...

  15. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  16. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  17. Passive heat acclimation improves skeletal muscle contractility in humans.

    Science.gov (United States)

    Racinais, S; Wilson, M G; Périard, J D

    2017-01-01

    The aim of this study was to investigate the effect of repeated passive heat exposure (i.e., acclimation) on muscle contractility in humans. Fourteen nonheat-acclimated males completed two trials including electrically evoked twitches and voluntary contractions in thermoneutral conditions [Cool: 24°C, 40% relative humidity (RH)] and hot ambient conditions in the hyperthermic state (Hot: 44-50°C, 50% RH) on consecutive days in a counterbalanced order. Rectal temperature was ~36.5°C in Cool and was maintained at ~39°C throughout Hot. Both trials were repeated after 11 days of passive heat acclimation (1 h per day, 48-50°C, 50% RH). Heat acclimation decreased core temperature in Cool (-0.2°C, P heat acclimation improved skeletal muscle contractility as evidenced by an increase in evoked peak twitch amplitude both in Cool (20.5 ± 3.6 vs. 22.0 ± 4.0 N·m) and Hot (20.5 ± 4.7 vs. 22.0 ± 4.0 N·m) (+9%, P heat acclimation improves skeletal muscle contractile function during electrically evoked and voluntary muscle contractions of different intensities both in Cool and Hot. These results suggest that repeated heat exposure may have important implications to passively maintain or even improve muscle function in a variety of performance and clinical settings. Copyright © 2017 the American Physiological Society.

  18. Purinergic effects on Na,K-ATPase activity differ in rat and human skeletal muscle

    DEFF Research Database (Denmark)

    Juel, Carsten; Nordsborg, Nikolai Baastrup; Bangsbo, Jens

    2014-01-01

    P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle.......P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle....

  19. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith

    2016-01-01

    . Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM...... at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...

  20. Carotid baroreceptor-muscle sympathetic relation in humans.

    Science.gov (United States)

    Rea, R F; Eckberg, D L

    1987-12-01

    The purpose of this study was to define the relation between carotid distending pressure and muscle sympathetic activity in humans. Carotid baroreceptors of nine healthy subjects were compressed or stretched for 5 s with graded neck pressure or suction (+40 to -65 mmHg), and muscle sympathetic nerve activity was recorded. The results delineate several features of human baroreflex function. First, the carotid-muscle sympathetic relation is well described by an inverse sigmoid function. Second, a linear relation exists between carotid distending pressure and sympathetic outflow over a range of approximately 25 mmHg. Third, sympathetic responses to changes of carotid pressures are asymmetric; increases of sympathetic activity during carotid compression are much greater than reductions of sympathetic activity during carotid stretch. Fourth, at rest, normal subjects operate near the threshold level for sympathetic excitation. Thus the carotid-muscle sympathetic baroreflex is poised to oppose reductions more effectively than elevations of arterial pressure, and the range of pressures over which the reflex is active is wider than thought hitherto.

  1. Fetal cardiac muscle contractility decreases with gestational age: a color-coded tissue velocity imaging study

    Directory of Open Access Journals (Sweden)

    Elmstedt Nina

    2012-05-01

    Full Text Available Abstract Background Present data regarding how the fetal heart works and develops throughout gestation is limited. However, the possibility to analyze the myocardial velocity profile provides new possibilities to gain further knowledge in this area. Thus, the objective of this study was to evaluate human fetal myocardial characteristics and deformation properties using color-coded tissue velocity imaging (TVI. Methods TVI recordings from 55 healthy fetuses, at 18 to 42 weeks of gestation, were acquired at a frame rate of 201–273 frames/s for offline analysis using software enabling retrieval of the myocardial velocity curve and 2D anatomical information. The measurements were taken from an apical four-chamber view, and the acquired data was correlated using regression analysis. Results Left ventricular length and width increased uniformly with gestational age. Atrioventricular plane displacement and the E’/A’ ratio also increased with gestational age, while a longitudinal shortening was demonstrated. Conclusions Fetal cardiac muscle contractility decreases with gestational age. As numerous fetal- and pregnancy-associated conditions directly influence the pumping function of the fetal heart, we believe that this new insight into the physiology of the human fetal cardiovascular system could contribute to make diagnosis and risk assessment easier and more accurate.

  2. Discrepancies between Skinned Single Muscle Fibres and Whole Thigh Muscle Function Characteristics in Young and Elderly Human Subjects

    Directory of Open Access Journals (Sweden)

    Hyunseok Jee

    2016-01-01

    Full Text Available We aimed to analyse the mechanical properties of skinned single muscle fibres derived from the vastus lateralis (VL muscle in relation to those of the whole intact thigh muscle and to compare any difference between young and older adults. Sixteen young men (29.25±4.65 years, 11 older men (71.45±2.94 years, 11 young women (29.64±4.88 years, and 7 older women (67.29±1.70 years were recruited. In vivo analyses were performed for mechanical properties such as isokinetic performance, isometric torque, and power. Specific force and maximum shortening velocity (Vo were measured with single muscle fibres. Sex difference showed greater impact on the functional properties of both the whole muscle (p<0.01 and single muscle fibres than aging (p<0.05. Sex difference, rather than aging, yielded more remarkable differences in gross mechanical properties in the single muscle fibre study in which significant differences between young men and young women were found only in the cross-sectional area and Vo (p<0.05. Age and sex differences reflect the mechanical properties of both single muscle fibres and whole thigh muscle, with the whole muscle yielding more prominent functional properties.

  3. Morphometric and Statistical Analysis of the Palmaris Longus Muscle in Human and Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Roqueline A. G. M. F. Aversi-Ferreira

    2014-01-01

    Full Text Available The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal joint flexor muscle in humans, a small vestigial forearm muscle; it is the most variable muscle in humans, showing variation in position, duplication, slips and could be reverted. It is frequently studied in papers about human anatomical variations in cadavers and in vivo, its variation has importance in medical clinic, surgery, radiological analysis, in studies about high-performance athletes, in genetics and anthropologic studies. Most studies about palmaris longus in humans are associated to frequency or case studies, but comparative anatomy in primates and comparative morphometry were not found in scientific literature. Comparative anatomy associated to morphometry of palmaris longus could explain the degeneration observed in this muscle in two of three of the great apes. Hypothetically, the comparison of the relative length of tendons and belly could indicate the pathway of the degeneration of this muscle, that is, the degeneration could be associated to increased tendon length and decreased belly from more primitive primates to those most derivate, that is, great apes to modern humans. In conclusion, in primates, the tendon of the palmaris longus increase from Lemuriformes to modern humans, that is, from arboreal to terrestrial primates and the muscle became weaker and tending to be missing.

  4. Age-related changes of muscle and plasma amino acids in healthy children.

    Science.gov (United States)

    Hammarqvist, Folke; Angsten, Gertrud; Meurling, Staffan; Andersson, Kerstin; Wernerman, Jan

    2010-07-01

    The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.

  5. Optimizing the measurement of mitochondrial protein synthesis in human skeletal muscle.

    Science.gov (United States)

    Burd, Nicholas A; Tardif, Nicolas; Rooyackers, Olav; van Loon, Luc J C

    2015-01-01

    The measurement of mitochondrial protein synthesis after food ingestion, contractile activity, and/or disease is often used to provide insight into skeletal muscle adaptations that occur in the longer term. Studies have shown that protein ingestion stimulates mitochondrial protein synthesis in human skeletal muscle. Minor differences in the stimulation of mitochondrial protein synthesis occur after a single bout of resistance or endurance exercise. There appear to be no measurable differences in mitochondrial protein synthesis between critically ill patients and aged-matched controls. However, the mitochondrial protein synthetic response is reduced at a more advanced age. In this paper, we discuss the challenges involved in the measurement of human skeletal muscle mitochondrial protein synthesis rates based on stable isotope amino acid tracer methods. Practical guidelines are discussed to improve the reliability of the measurement of mitochondrial protein synthesis rates. The value of the measurement of mitochondrial protein synthesis after a single meal or exercise bout on the prediction of the longer term skeletal muscle mass and performance outcomes in both the healthy and disease populations requires more work, but we emphasize that the measurements need to be reliable to be of any value to the field.

  6. Redox Signaling in Skeletal Muscle: Role of Aging and Exercise

    Science.gov (United States)

    Ji, Li Li

    2015-01-01

    Skeletal muscle contraction is associated with the production of ROS due to altered O[subscript 2] distribution and flux in the cell. Despite a highly efficient antioxidant defense, a small surplus of ROS, such as hydrogen peroxide and nitric oxide, may serve as signaling molecules to stimulate cellular adaptation to reach new homeostasis largely…

  7. Muscle Gene Expression Patterns in Human Rotator Cuff Pathology

    Science.gov (United States)

    Choo, Alexander; McCarthy, Meagan; Pichika, Rajeswari; Sato, Eugene J.; Lieber, Richard L.; Schenk, Simon; Lane, John G.; Ward, Samuel R.

    2014-01-01

    Background: Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology. Methods: Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis. Results: Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear. Conclusions: Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of

  8. In skeletal muscle advanced glycation end products (AGEs) inhibit insulin action and induce the formation of multimolecular complexes including the receptor for AGEs.

    Science.gov (United States)

    Cassese, Angela; Esposito, Iolanda; Fiory, Francesca; Barbagallo, Alessia P M; Paturzo, Flora; Mirra, Paola; Ulianich, Luca; Giacco, Ferdinando; Iadicicco, Claudia; Lombardi, Angela; Oriente, Francesco; Van Obberghen, Emmanuel; Beguinot, Francesco; Formisano, Pietro; Miele, Claudia

    2008-12-26

    Chronic hyperglycemia promotes insulin resistance at least in part by increasing the formation of advanced glycation end products (AGEs). We have previously shown that in L6 myotubes human glycated albumin (HGA) induces insulin resistance by activating protein kinase Calpha (PKCalpha). Here we show that HGA-induced PKCalpha activation is mediated by Src. Coprecipitation experiments showed that Src interacts with both the receptor for AGE (RAGE) and PKCalpha in HGA-treated L6 cells. A direct interaction of PKCalpha with Src and insulin receptor substrate-1 (IRS-1) has also been detected. In addition, silencing of IRS-1 expression abolished HGA-induced RAGE-PKCalpha co-precipitation. AGEs were able to induce insulin resistance also in vivo, as insulin tolerance tests revealed a significant impairment of insulin sensitivity in C57/BL6 mice fed a high AGEs diet (HAD). In tibialis muscle of HAD-fed mice, insulin-induced glucose uptake and protein kinase B phosphorylation were reduced. This was paralleled by a 2.5-fold increase in PKCalpha activity. Similarly to in vitro observations, Src phosphorylation was increased in tibialis muscle of HAD-fed mice, and co-precipitation experiments showed that Src interacts with both RAGE and PKCalpha. These results indicate that AGEs impairment of insulin action in the muscle might be mediated by the formation of a multimolecular complex including RAGE/IRS-1/Src and PKCalpha.

  9. Reflex influences on muscle spindle activity in relaxed human leg muscles.

    Science.gov (United States)

    Gandevia, S C; Miller, S; Aniss, A M; Burke, D

    1986-07-01

    The study was designed to determine whether low-threshold cutaneous and muscle afferents from the foot reflexly activate gamma-motoneurons innervating relaxed muscles of the leg. In 15 experiments multiunit recordings were made from 21 nerve fascicles innervating triceps surae or tibialis anterior. In a further nine experiments the activity of 19 identified single muscle spindle afferents was recorded, 13 from triceps surae, 5 from tibialis anterior, and 1 from extensor digitorum longus. Trains of electrical stimuli (5 stimuli, 300 Hz) were delivered to the sural nerve at the ankle (intensity, twice sensory threshold) and the posterior tibial nerve at the ankle (intensity, 1.1 times motor threshold for the small muscles of the foot). In addition, a tap on the appropriate tendon at varying times after the stimuli was used to assess the dynamic responsiveness of the afferents under study. The conditioning electrical stimuli did not change the discharge of single spindle afferents. Recordings of rectified and averaged multiunit activity also revealed no change in the overall level of background neural activity following the electrical stimuli. The afferent responses to tendon taps did not differ significantly whether or not they were preceded by stimulation of the sural or posterior tibial nerves. These results suggest that low-threshold afferents from the foot do not produce significant activation of fusimotor neurons in relaxed leg muscles, at least as judged by their ability to alter the discharge of muscle spindle afferents. As there may be no effective background activity in fusimotor neurons innervating relaxed human muscles, it is possible that these inputs from the foot could influence the fusimotor system during voluntary contractions when the fusimotor neurons have been brought to firing threshold. In one subject trains of stimuli were delivered to the posterior tibial nerve at painful levels (30 times motor threshold). They produced an acceleration of the

  10. Animal and human models to understand ageing.

    Science.gov (United States)

    Lees, Hayley; Walters, Hannah; Cox, Lynne S

    2016-11-01

    Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

  11. Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle: a comparative study of newborn, adult and aged rats

    DEFF Research Database (Denmark)

    Andersson, A M; Olsen, M; Zhernosekov, D

    1993-01-01

    report quantitative and qualitative changes in NCAM protein and mRNA forms during aging in normal rat skeletal muscle. Determination of the amount of NCAM by e.l.i.s.a. showed that the level decreased from perinatal to adult age, followed by a considerable increase in 24-month-old rat muscle. Thus NCAM...... virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2......Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here...

  12. Skeletal muscle contractile function and neuromuscular performance in Zmpste24 -/- mice, a murine model of human progeria.

    Science.gov (United States)

    Greising, Sarah M; Call, Jarrod A; Lund, Troy C; Blazar, Bruce R; Tolar, Jakub; Lowe, Dawn A

    2012-08-01

    Human progeroid syndromes and premature aging mouse models present as segmental, accelerated aging because some tissues and not others are affected. Skeletal muscle is detrimentally changed by normal aging but whether it is an affected tissue in progeria has not been resolved. We hypothesized that mice which mimic Hutchinson-Gilford progeria syndrome would exhibit age-related alterations of skeletal muscle. Zmpste24 (-/-) and Zmpste24 (+/+) littermates were assessed for skeletal muscle functions, histo-morphological characteristics, and ankle joint mechanics. Twenty-four-hour active time, ambulation, grip strength, and whole body tension were evaluated as markers of neuromuscular performance, each of which was at least 33% lower in Zmpste24 (-/-) mice compared with littermates (p normal. Ankle range of motion was 70% lower and plantar- and dorsiflexion passive torques were nearly 3-fold greater in Zmpste24 (-/-) than Zmpste24 (+/+) mice (p ≤ 0.01). The combined factors of muscle atrophy, collagen accumulation, and perturbed joint mechanics likely contributed to poor neuromuscular performance and selective muscle weakness displayed by Zmpste24 (-/-)mice. In summary, these characteristics are similar to those of aged mice indicating accelerated aging of skeletal muscle in progeria.

  13. Human intersegmental reflexes from intercostal afferents to scalene muscles.

    Science.gov (United States)

    McBain, Rachel A; Taylor, Janet L; Gorman, Robert B; Gandevia, Simon C; Butler, Jane E

    2016-10-01

    What is the central question of this study? The aim was to determine whether specific reflex connections operate between intercostal afferents and the scalene muscles in humans, and whether these connections operate after a clinically complete cervical spinal cord injury. What is the main finding and its importance? This is the first description of a short-latency inhibitory reflex connection between intercostal afferents from intercostal spaces to the scalene muscles in able-bodied participants. We suggest that this reflex is mediated by large-diameter afferents. This intercostal-to-scalene inhibitory reflex is absent after cervical spinal cord injury and may provide a way to monitor the progress of the injury. Short-latency intersegmental reflexes have been described for various respiratory muscles in animals. In humans, however, only short-latency reflex responses to phrenic nerve stimulation have been described. Here, we examined the reflex connections between intercostal afferents and scalene muscles in humans. Surface EMG recordings were made from scalene muscles bilaterally, in seven able-bodied participants and seven participants with motor- and sensory-complete cervical spinal cord injury (median 32 years postinjury, range 5 months to 44 years). We recorded the reflex responses produced by stimulation of the eighth or tenth left intercostal nerve. A short-latency (∼38 ms) inhibitory reflex was evident in able-bodied participants, in ipsilateral and contralateral scalene muscles. This bilateral intersegmental inhibitory reflex occurred in 46% of recordings at low stimulus intensities (at three times motor threshold). It was more frequent (in 75-85% of recordings) at higher stimulus intensities (six and nine times motor threshold), but onset latency (38 ± 9 ms, mean ± SD) and the size of inhibition (23 ± 10%) did not change with stimulus intensity. The reflex was absent in all participants with spinal cord injury. As the intercostal

  14. Muscle specific miRNAs are induced by testosterone and independently upregulated by age

    DEFF Research Database (Denmark)

    Nielsen, Søren; Hvid, Thine; Kelly, Meghan;

    2014-01-01

    Age dependent decline in skeletal muscle function leads to impaired metabolic flexibility in elderly individuals. Physical activity and testosterone treatment have proven efficient strategies for delaying this condition. However, a common molecular pathway has not been identified. Muscle specific...... miRNAs (myomiRs) regulate metabolic pathways in skeletal muscle, are regulated by physical activity, and have response elements for testosterone in their promoter region. We therefore hypothesized that myomiRs would be regulated in skeletal muscle during aging. We further investigated any potential...... gender-dependent regulation of these miRNAs. We found that the myomiRs miR-1, miR-133a, and miR-133b were increased in skeletal muscle of elderly men compared to younger men. In addition, miR-133a/133b expression was markedly higher in women compared to men. Elimination of circulating testosterone in men...

  15. Age-related decline in muscle mass and muscle function in Flemish Caucasians: a 10-year follow-up.

    Science.gov (United States)

    Charlier, Ruben; Knaeps, Sara; Mertens, Evelien; Van Roie, Evelien; Delecluse, Christophe; Lefevre, Johan; Thomis, Martine

    2016-04-01

    Aging is a complex process that is accompanied with changes in both muscle mass and muscle function (strength and performance). Therefore, the current longitudinal study aimed to provide a better insight in 10-year aging-related changes in whole-body muscle mass and strength performance of the leg extensors during the adult life span. Data were gathered within the framework of the first- (2002-2004: baseline) and third-generation Flemish Policy Research Center Sport (2012-2014: follow-up). Results are based on muscle characteristics data of 591 Flemish Caucasian adults (19-73 years, 381 men). Skeletal muscle mass (SMM) was determined with bioelectrical impedance analysis. Biodex Medical System 3® dynamometer was used to measure isometric (PTstatic120°) and isokinetic (PTdynamic60° and PTdynamic240°) strength, ballistic movement speed (S 20 %), and muscular endurance (work) of the knee extensors. Overall strength performance was higher at both evaluation moments in men compared to women (p < 0.01). But only S 20 % declined significantly faster in men compared to women (p < 0.01). Age and baseline strength performance were negatively related with the change in strength performance, even when corrected for SMM, protein intake, and energy expenditure during sports (E sport). In conclusion, strength performance was not associated with E sport in this study, but protein intake was associated with isometric strength in men, and with ballistic and isokinetic strength in women. Changes in S 20 % were significantly greater in men compared to women. Baseline values of strength performance and age were associated with changes in strength performance parameters, even after correction for SMM, protein intake, and E sport.

  16. Changes in the Muscle strength and functional performance of healthy women with aging

    Directory of Open Access Journals (Sweden)

    Roghayeh Mousavikhatir

    2012-08-01

    Full Text Available Abstract Background: Lower limbs antigravity muscles weakness and decreased functional ability have significant role in falling. The aim of this study was to find the effects of aging on muscle strength and functional ability, determining the range of decreasing strength and functional ability and relationship between them in healthy women. Methods: Across-section study was performed on 101 healthy women aged 21-80 years. The participants were divided into six age groups. The maximum isometric strength of four muscle groups was measured using a hand-held dynamometer bilaterally. The functional ability was measured with functional reach (FR, timed get up and go (TGUG, single leg stance (SLS, and stairs walking (SW tests. Results: Muscle strength changes were not significant between 21-40 years of age, but decreased significantly thereafter. Also, there was a significant relationship between muscle strength and functional ability in age groups. Conclusion: Both muscle strength and functional ability is reduced as a result of aging, but the decrease in functional ability can be detected earlier.

  17. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    was to investigate whether subdivisions within the human trapezius can be independently activated by voluntary command using biofeedback guidance. Bipolar electromyographical electrodes were situated on four subdivisions of the trapezius muscle. The threshold for "active" and "rest" for each subdivision was set...... to >12% and biofeedback from each of the four trapezius subdivisions, 11 of 15 subjects learned selective activation of at least one of the four anatomical subdivisions of the trapezius...

  18. Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling

    Science.gov (United States)

    Older individuals have a reduced capacity to induce muscle hypertrophy with resistance exercise (RE), which may contribute to the age-induced loss of muscle mass and function, sarcopenia. We tested the novel hypothesis that dysregulation of microRNAs (miRNAs) may contribute to reduced muscle plastic...

  19. Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth.

    Science.gov (United States)

    Farup, Jean; Rahbek, Stine Klejs; Riis, Simon; Vendelbo, Mikkel Holm; Paoli, Frank de; Vissing, Kristian

    2014-10-15

    Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type-specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P hypertrophy correlated with whole muscle hypertrophy exclusively following Conc training (P eccentric resistance training while type II fiber hypertrophy was accentuated when combining concentric resistance training with whey protein supplementation.

  20. The challenges of human population ageing

    Science.gov (United States)

    Sander, Miriam; Oxlund, Bjarke; Jespersen, Astrid; Krasnik, Allan; Mortensen, Erik Lykke; Westendorp, Rudi Gerardus Johannes; Rasmussen, Lene Juel

    2015-01-01

    The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical, social, public health and public policy challenges, whose full implications on a societal level are only just beginning to be fully appreciated. Some of these implications are discussed in this commentary, an outcome of Cultures of Health and Ageing, a conference co-sponsored by the University of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20–21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create ‘age-friendly’ societies and promote ‘ageing-in-community’? what tools will effectively promote social engagement and prevent social detachment among older individuals? is there a risk that further extension of human lifespan would be a greater burden to the individual and to society than is warranted by the potential benefit of longer life? PMID:25452294

  1. Premature birth is associated with not fully differentiated contractile smooth muscle cells in human umbilical artery.

    Science.gov (United States)

    Roffino, S; Lamy, E; Foucault-Bertaud, A; Risso, F; Reboul, R; Tellier, E; Chareyre, C; Dignat-George, F; Simeoni, U; Charpiot, P

    2012-06-01

    Smooth muscle cells (SMCs) participate to the regulation of peripheral arterial resistance and blood pressure. To assume their function, SMCs differentiate throughout the normal vascular development from a synthetic phenotype towards a fully differentiated contractile phenotype by acquiring a repertoire of proteins involved in contraction. In human fetal muscular arteries and umbilical arteries (UAs), no data are available regarding the differentiation of SMCs during the last trimester of gestation. The objective of this study was to characterize the phenotype of SMCs during this gestation period in human UAs. We investigated the phenotype of SMCs in human UAs from very preterm (28-31 weeks of gestation), late preterm (32-35 weeks) and term (37-41 weeks) newborns using biochemical and immunohistochemical detection of α-actin, smooth muscle myosin heavy chain, smoothelin, and non-muscle myosin heavy chain. We found that the number of SMCs positive for smoothelin in UAs increased with gestational age. Western blot analysis revealed a higher content of smoothelin in term compared to very preterm UAs. These results show that SMCs in human UAs gradually acquire a fully differentiated contractile phenotype during the last trimester of gestation and thus that premature birth is associated with not fully differentiated contractile SMCs in human UAs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. ROLE OF AUTOPHAGY IN AGE-RELATED MUSCLE LOSS

    OpenAIRE

    Lo Verso, Francesca

    2014-01-01

    Autophagy is an ubiquitous degradation system, that is conserved through species. Cells activate autophagy to degrade long-lived proteins, damaged organelles or portions of cytoplasm, that are engulfed in double-membrane vesicles called autophagosomes, that ultimately fuse to lysosomes, where the cargo is degraded and breakdown products are recycled to sustain cellular energetic demands. Skeletal muscle is the most abundant tissue in mammals and controls 80% of the blood glucose. We have r...

  3. Aging time of five muscles from carcass of Nellore young bulls

    Directory of Open Access Journals (Sweden)

    Laís Regina Simonetti

    2015-10-01

    Full Text Available This trial aimed to assess the qualitative traits of five muscles of 14 Nellore bulls with 450 kg ± 30.7 kg BW, feedlot fed for 60 days. After slaughter and carcass chilling, samples of the Biceps femoris (BF, Longissimus (LD, Gluteus medius (GM, Semitendinosus (ST and Trapezius thoracis (TT muscles were collected, vacuum-packed and aged at 0 to 2 ºC for 1, 7 and 14 days and subsequently stored at –20ºC for chemical and quality analysis. The pH, shear force, water holding capacity, cooking losses, meat color and ether extract were evaluated in all aging times. Data were analyzed in a split-plot design using the PROC MIXED procedure of SAS. Aging affected quality traits and chemical properties of the meat, improving aspects, such as tenderness (p < 0.01 and lightness (p < 0.01. The Trapezius thoracis muscle has a higher color stability compared with the Longissimus muscle. Aging is not recommended for the ST muscle because the tenderness is not improved. The GM and BF muscles are tender on the first day, and the aging process is indicated for these cuts for adding value to the beef.

  4. Comparison of MRI and DXA to measure muscle size and age-related atrophy in thigh muscles.

    Science.gov (United States)

    Maden-Wilkinson, T M; Degens, H; Jones, D A; McPhee, J S

    2013-09-01

    Magnetic resonance imaging (MRI) and dual-energy x-ray absorptiometry (DXA) were used to examine the thigh lean mass in young and old men and women. A whole-body DXA scan was used to estimate thigh lean mass in young (20 men; 22.4±3.1y; 18 women; 22.1±2.0y) and older adults (25 men; 72.3±4.9y; 28 women; 72.0±4.5y). Thigh lean mass determined with a thigh scan on the DXA or full thigh MRI scans were compared. Although the thigh lean mass quantified by DXA and MRI in young and older participants were correlated (R(2)=0.88; pmuscles in the older than young individuals, while the other thigh muscles were only 18% smaller. DXA underestimates the age-related loss of thigh muscle mass in comparison to MRI. The quadriceps muscles were more susceptible to age-related atrophy compared with other thigh muscles.

  5. Bionic Humans Using EAP as Artificial Muscles Reality and Challenges

    Directory of Open Access Journals (Sweden)

    Yoseph Bar-Cohen

    2008-11-01

    Full Text Available For many years, the idea of a human with bionic muscles immediately conjures up science fiction images of a TV series superhuman character that was implanted with bionic muscles and portrayed with strength and speed far superior to any normal human. As fantastic as this idea may seem, recent developments in electroactive polymers (EAP may one day make such bionics possible. Polymers that exhibit large displacement in response to stimulation that is other than electrical signal were known for many years. Initially, EAP received relatively little attention due to their limited actuation capability. However, in the recent years, the view of the EAP materials has changed due to the introduction of effective new materials that significantly surpassed the capability of the widely used piezoelectric polymer, PVDF. As this technology continues to evolve, novel mechanisms that are biologically inspired are expected to emerge. EAP materials can potentially provide actuation with lifelike response and more flexible configurations. While further improvements in performance and robustness are still needed, there already have been several reported successes. In recognition of the need for cooperation in this multidisciplinary field, the author initiated and organized a series of international forums that are leading to a growing number of research and development projects and to great advances in the field. In 1999, he challenged the worldwide science and engineering community of EAP experts to develop a robotic arm that is actuated by artificial muscles to win a wrestling match against a human opponent. In this paper, the field of EAP as artificial muscles will be reviewed covering the state of the art, the challenges and the vision for the progress in future years.

  6. Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle.

    Science.gov (United States)

    Chalil, Sreeda; Pierre, Nicolas; Bakker, Astrid D; Manders, Ralph J; Pletsers, Annelies; Francaux, Marc; Klein-Nulend, Jenneke; Jaspers, Richard T; Deldicque, Louise

    2015-12-25

    Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1α was higher in EDL, and phospho-eIF2α was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging.

  7. Localization and function of ATP-sensitive potassium channels in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Jens Jung; Kristensen, Michael; Hellsten, Ylva

    2003-01-01

    The present study investigated the localization of ATP-sensitive K+ (KATP) channels in human skeletal muscle and the functional importance of these channels for human muscle K+ distribution at rest and during muscle activity. Membrane fractionation based on the giant vesicle technique...

  8. Effect of resistance training on neuromuscular junctions of young and aged muscles featuring different recruitment patterns.

    Science.gov (United States)

    Deschenes, Michael R; Sherman, E Grace; Roby, Mackenzie A; Glass, Emily K; Harris, M Brennan

    2015-03-01

    To examine the effects of aging on neuromuscular adaptations to resistance training (i.e., weight lifting), young (9 months of age) and aged (20 months of age) male rats either participated in a 7-week ladder climbing protocol with additional weight attached to their tails or served as controls (n = 10/group). At the conclusion, rats were euthanized and hindlimb muscles were quickly removed and frozen for later analysis. Longitudinal sections of the soleus and plantaris muscles were collected, and pre- and postsynaptic features of neuromuscular junctions (NMJs) were visualized with immunofluorescence staining procedures. Cross-sections of the same muscles were histochemically stained to determine myofiber profiles (fiber type and size). Statistical analysis was by two-way ANOVA (main effects of age and treatment) with significance set at P ≤ 0.05. Results revealed that training-induced remodeling of NMJs was evident only at the postsynaptic endplate region of soleus fast-twitch myofibers. In contrast, aging was associated with pre- and postsynaptic remodeling in fast- and slow-twitch myofibers of the plantaris. Although both the soleus and the plantaris muscles failed to display either training or aging-related alterations in myofiber size, aged plantaris muscles exhibited an increased expression of type I (slow-twitch) myofibers in conjunction with a reduced percentage of type II (fast-twitch) myofibers, suggesting early stages of sarcopenia. These data demonstrate the high degree of specificity of synaptic modifications made in response to exercise and aging and that the sparsely recruited plantaris is more vulnerable to the effects of aging than the more frequently recruited soleus muscle.

  9. Age differences in dynamic fatigability and variability of arm and leg muscles: Associations with physical function.

    Science.gov (United States)

    Senefeld, Jonathon; Yoon, Tejin; Hunter, Sandra K

    2017-01-01

    It is not known whether the age-related increase in fatigability of fast dynamic contractions in lower limb muscles also occurs in upper limb muscles. We compared age-related fatigability and variability of maximal-effort repeated dynamic contractions in the knee extensor and elbow flexor muscles; and determined associations between fatigability, variability of velocity between contractions and functional performance. 35 young (16 males; 21.0±2.6years) and 32 old (18 males; 71.3±6.2years) adults performed a dynamic fatiguing task involving 90 maximal-effort, fast, concentric, isotonic contractions (1 contraction/3s) with a load equivalent to 20% maximal voluntary isometric contraction (MVIC) torque with the elbow flexor and knee extensor muscles on separate days. Old adults also performed tests of balance and walking endurance. Old adults had greater fatigue-related reductions in peak velocity compared with young adults for both the elbow flexor and knee extensor muscles (P0.05). Old adults had greater variability of peak velocity during the knee extensor, but not during the elbow flexor fatiguing task. The age difference in fatigability was greater for the knee extensor muscles (35.9%) compared with elbow flexor muscles (9.7%, P<0.05). Less fatigability of the knee extensor muscles was associated with greater walking endurance (r=-0.34, P=0.048) and balance (r=-0.41, P=0.014) among old adults. An age-related increase in fatigability of a dynamic fatiguing task was greater for the knee extensor compared with the elbow flexor muscles in males and females, and greater fatigability was associated with lesser walking endurance and balance. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Ca2+ sparks as a plastic signal for skeletal muscle health, aging, and dystrophy

    Institute of Scientific and Technical Information of China (English)

    Noah WEISLEDER; Jian-jie MA

    2006-01-01

    Ca2+ sparks are the elementary units of intracellular Ca2+ signaling in striated muscle cells revealed as localized Ca2+ release events from sarcoplasmic reticulum(SR)by confocal microscopy.While Ca2+ sparks are well defined in cardiac muscle,there has been a general belief that these localized Ca2+ release events are rare in intact adult mammalian skeletal muscle.Several laboratories determined that Ca2+ sparks in mammalian skeletal muscle could only be observed in large numbers when the sarcolemmal membranes are permeabilized or the SR Ca2+ content is artificially manipulated,thus the cellular and molecular mechanisms underlying the regulation of Ca2+ sparks in skeletal muscle remain largely unexplored.Recently,we discovered that membrane deformation generated by osmotic stress induced a robust Ca2+ spark response confined in close spatial proximity to the sarcolemmal membrane in intact mouse muscle fibers.In addition to Ca2+ sparks,prolonged Ca2+ transients, termed Ca2+ bursts, are also identified in intact skeletal muscle.These induced Ca2+ release events are reversible and repeatable,revealing a plastic nature in young muscle fibers.In contrast, induced Ca2+ sparks in aged muscle are transient and cannot be re-stimulated.Dystrophic muscle fibers display uncontrolled Ca2+ sparks,where osmotic stress-induced Ca2+ sparks are not reversible and they are no longer spatially restricted to the sarcolemmal membrane.An understanding of the mechanisms that underlie generation of osmotic stressinduced Ca2+ sparks in skeletal muscle and how these mechanisms are altered in pathology, will contribute to our understanding of the regulation of Ca2+ homeostasis in muscle physiology and pathophysiology.

  11. Age-related functional changes and susceptibility to eccentric contraction-induced damage in skeletal muscle cell

    Directory of Open Access Journals (Sweden)

    Seung-Jun Choi

    2016-09-01

    Full Text Available Depending upon external loading conditions, skeletal muscles can either shorten, lengthen, or remain at a fixed length as they produce force. Fixed-end or isometric contractions stabilize joints and allow muscles to act as active struts during locomotion. Active muscles dissipate energy when they are lengthened by an external force that exceeds their current force producing capacity. These unaccustomed eccentric activities often lead to muscle weakness, soreness, and inflammation. During aging, the ability to produce force under these conditions is reduced and appears to be due to not only reductions in muscle mass but also to alterations in the basic mechanisms of contraction. These alterations include impairments in the excitation–contraction process, and the action of the cross-bridges. Also, it is well known that age-related skeletal muscle atrophy is characterized by a preferential atrophy of fast fibers, and increased susceptibility to fast muscle fiber when aged muscles are exposed to eccentric contraction followed by the impaired recovery process has been reported. Taken together, the selective loss of fast muscle fiber in aged muscle could be affected by eccentric-induced muscle damage, which has significant implication to identify the etiology of the age-related functional changes. Therefore, in this review the alteration of age-related muscle function and its impact to/of eccentric induced muscle damage and recovery will be addressed in detail.

  12. Adenosine concentrations in the interstitium of resting and contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Maclean, D.; Rådegran, G.

    1998-01-01

    effect remain unanswered. METHODS AND RESULTS: The interstitial adenosine concentration was determined in the vastus lateralis muscle of healthy humans via dialysis probes inserted in the muscle. The probes were perfused with buffer, and the dialysate samples were collected at rest and during graded knee...... and demonstrates that adenosine and its precursors increase in the exercising muscle interstitium, at a rate associated with intensity of muscle contraction and the magnitude of muscle blood flow....

  13. Ultrastructure of striated muscle fibers in the middle third of the human esophagus

    OpenAIRE

    Faussone-Pellegrini, M.S; Cortesini, C.

    1986-01-01

    Striated muscle fibers and .their spatial relationship to smooth muscle cells have been studied in the middle third of human esophagus. Biopsies were obtained from 3 patients during surgery. In both the circular and longitudinal layers, the muscle coat of this transition zone was composed of fascicles of uniform dimensioi~ (100-200 pm of diameter); some of these bundles were made up of striated muscle fibers, others were pure bundles of smooth muscle cells and ...

  14. Human skeletal muscle fibre types and force: velocity properties.

    Science.gov (United States)

    MacIntosh, B R; Herzog, W; Suter, E; Wiley, J P; Sokolosky, J

    1993-01-01

    It has been reported that there is a relationship between power output and fibre type distribution in mixed muscle. The strength of this relationship is greater in the range of 3-8 rad.s-1 during knee extension compared to slower or faster angular knee extensor speeds. A mathematical model of the force: velocity properties of muscle with various combinations of fast- and slow-twitch fibres may provide insight into why specific velocities may give better predictions of fibre type distribution. In this paper, a mathematical model of the force:velocity relationship for mixed muscle is presented. This model demonstrates that peak power and optimal velocity should be predictive of fibre distribution and that the greatest fibre type discrimination in human knee extensor muscles should occur with measurement of power output at an angular velocity just greater than 7 rad.s-1. Measurements of torque:angular velocity relationships for knee extension on an isokinetic dynamometer and fibre type distribution in biopsies of vastus lateralis muscles were made on 31 subjects. Peak power and optimal velocity were determined in three ways: (1) direct measurement, (2) linear regression, and (3) fitting to the Hill equation. Estimation of peak power and optimal velocity using the Hill equation gave the best correlation with fibre type distribution (r < 0.5 for peak power or optimal velocity and percentage of fast-twitch fibres). The results of this study confirm that prediction of fibre type distribution is facilitated by measurement of peak power at optimal velocity and that fitting of the data to the Hill equation is a suitable method for evaluation of these parameters.

  15. Modelling in vivo skeletal muscle ageing in vitro using three-dimensional bioengineered constructs.

    Science.gov (United States)

    Sharples, Adam P; Player, Darren J; Martin, Neil R W; Mudera, Vivek; Stewart, Claire E; Lewis, Mark P

    2012-12-01

    Degeneration of skeletal muscle (SkM) with age (sarcopenia) is a major contributor to functional decline, morbidity and mortality. Methodological implications often make it difficult to embark on interventions in already frail and diseased elderly individuals. Using in vitro three-dimensional (3D) bioengineered skeletal muscle constructs that model aged phenotypes and incorporate a representative extracellular matrix (collagen), are under tension, and display morphological and transcript expression of mature skeletal muscle may more accurately characterize the SkM niche. Furthermore, an in vitro model would provide greater experimental manipulation with regard to gene, pharmacological and exercise (mechanical stretch/electrical stimulation) therapies and thus strategies for combating muscle wasting with age. The present study utilized multiple population-doubled (MPD) murine myoblasts compared with parental controls (CON), previously shown to have an aged phenotype in monolayer cultures (Sharples et al., 2011), seeded into 3D type I collagen matrices under uniaxial tension. 3D bioengineered constructs incorporating MPD cells had reduced myotube size and diameter vs. CON constructs. MPD constructs were characterized by reduced peak force development over 24 h after cell seeding, reduced transcript expression of remodelling matrix metalloproteinases, MMP2 and MMP9, with reduced differentiation/hypertrophic potential shown by reduced IGF-I, IGF-IR, IGF-IEa, MGF mRNA. Increased IGFBP2 and myostatin in MPD vs. CON constructs also suggested impaired differentiation/reduced regenerative potential. Overall, 3D bioengineered skeletal muscle constructs represent an in vitro model of the in vivo cell niche with MPD constructs displaying similar characteristics to ageing/atrophied muscle in vivo, thus potentially providing a future test bed for therapeutic interventions to contest muscle degeneration with age. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd

  16. Contemporary views on human aging and longevity

    Directory of Open Access Journals (Sweden)

    Chmielewski Piotr

    2016-06-01

    Full Text Available Aging is currently stimulating intense interest of both researchers and the general public. In developed countries, the average life expectancy has increased by roughly 30 years within the last century, and human senescence has been delayed by around a decade. Although aging is arguably the most familiar aspect of human biology, its proximate and ultimate causes have not been elucidated fully and understood yet. Nowadays there are two main approaches to the ultimate causes of aging. These are deterministic and stochastic models. The proximate theories constitute a distinct group of explanations. They focus on mechanistic causes of aging. In this view, there is no reason to believe that there is only one biological mechanism responsible for aging. The aging process is highly complex and results from an accumulation of random molecular damage. Currently, the disposable soma theory (DST, proposed by Thomas Kirkwood, is the most influential and coherent line of reasoning in biogerontology. This model does not postulate any particular mechanism underpinning somatic defense. Therefore, it is compatible with various models, including mechanistic and evolutionary explanations. Recently, however, an interesting theory of hyper-function of mTOR as a more direct cause of aging has been formulated by Mikhail Blagosklonny, offering an entirely different approach to numerous problems and paradoxes in current biogerontology. In this view, aging is quasi-programmed, which means that it is an aimless continuation of developmental growth. This mTOR-centric model allows the prediction of completely new relationships. The aim of this article is to present and compare the views of both parties in the dispute, based on the results of some recent experimental studies, and the contemporary knowledge of selected major aspects of human aging and longevity

  17. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... sympathetic vasoconstriction. ATP is released into plasma from erythrocytes and endothelial cells and the plasma concentration increases in both the feeding artery and the vein draining the contracting skeletal muscle. Adenosine also stimulates the formation of NO and prostaglandins, but the plasma adenosine...... and endothelial cells. In the interstitium, both ATP and adenosine stimulate the formation of NO and prostaglandins, but ATP has also been suggested to induce vasoconstriction and stimulate afferent nerves that signal to increase sympathetic nerve activity. Adenosine has been shown to contribute to exercise...

  18. Hypotension during endotoxemia in aged humans

    DEFF Research Database (Denmark)

    Krabbe, Karen Suarez; Kemp, Helle Bruunsgaard; Qvist, Jesper

    2001-01-01

    BACKGROUND: and objective The aim of this study was to determine possible age-associated differences in human blood pressure regulation during an immunological challenge in healthy subjects. METHODS: Eight healthy young volunteers (median age 24 yr) and nine healthy elderly volunteers (median age....... Increased plasma epinephrine concentrations were found 2-3 h after endotoxin administration in both groups. Five hours after the endotoxin challenge, the epinephrine concentration had returned to control values in the elderly group only, in spite of decreased blood pressure. CONCLUSION: In conclusion...

  19. Induction of GLUT-1 protein in adult human skeletal muscle fibers

    DEFF Research Database (Denmark)

    Gaster, M; Franch, J; Staehr, P

    2000-01-01

    fibers. Metabolic stress (obesity, non-insulin-dependent diabetes mellitus), contractile activity (training), and conditions of de- and reinnervation (amyotrophic lateral sclerosis) could not induce GLUT-1 expression in human muscle fibers. However, regenerating muscle fibers in polymyositis expressed...

  20. Skeletal muscle vasodilation during systemic hypoxia in humans.

    Science.gov (United States)

    Dinenno, Frank A

    2016-01-15

    In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that 1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; 2) PGs do not normally contribute to vascular tone during hypoxia, however, they do affect vascular tone when NO is inhibited; 3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and 4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, skeletal muscle blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts augmented vasodilation and hyperemia compared with control (normoxic) conditions by ∼50%; however, in contrast to hypoxia alone, the response is not abolished, suggesting that other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release, or nitrite reduction to NO, or both likely play a role in regulating this response.

  1. Peak muscle mass in young men and sarcopenia in the ageing male

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost Munk; Nielsen, T L; Brixen, K

    2015-01-01

    The prevalence of sarcopenia increases with age. The diagnosis of sarcopenia relies in part on normative data on muscle mass, but these data are lacking. This study provides population-based reference data on muscle mass in young men, and these results may be used clinically for the diagnosis...... of sarcopenia in men. INTRODUCTION: The ageing population increases the prevalence of sarcopenia. Estimation of normative data on muscle mass in young men during the peak of anabolic hormones is necessary for the diagnosis of sarcopenia in ageing males. The purposes of this study were to provide population......-based reference data on lean body mass (LBM) in young men during the time of peak levels of GH/IGF-1 and testosterone and further to apply the reference data on a population-based sample of men aged 60-74 years to estimate the prevalence of sarcopenia. METHODS: This is a cross-sectional, population-based single...

  2. Age-dependent Muscle Adaptation after Chronic Stretch-shortening Contractions in Rats.

    Science.gov (United States)

    Rader, Erik P; Layner, KaylaN; Triscuit, Alyssa M; Chetlin, Robert D; Ensey, James; Baker, Brent A

    2016-01-01

    Age-related differences in contraction-induced adaptation have been well characterized especially for young and old rodent models but much less so at intermediate ages. Therefore, additional research is warranted to determine to what extent alterations in adaptation are due to maturation versus aging per se. The purpose of our study was to evaluate muscles of Fisher 344XBrown Norway rats of various ages following one month of exposure to stretch-shortening contractions (SSCs). With exposure, muscles mass increased by ~10% for 27 and 30 month old rats vs. ~20% for 3 and 6 month old rats (P muscle performance in general beginning at late adulthood. Such findings motivate careful investigation to determine appropriate SSC exposures at all stages of life.

  3. Effect of Tongue Exercise on Protrusive Force and Muscle Fiber Area in Aging Rats

    Science.gov (United States)

    Connor, Nadine P.; Russell, John A.; Wang, Hao; Jackson, Michelle A.; Mann, Laura; Kluender, Keith

    2009-01-01

    Purpose: Age-related changes in tongue function may contribute to dysphagia in elderly people. The authors' purpose was to investigate whether aged rats that have undergone tongue exercise would manifest increased protrusive tongue forces and increased genioglossus (GG) muscle fiber cross-sectional areas. Method: Forty-eight young adult,…

  4. Effect of Tongue Exercise on Protrusive Force and Muscle Fiber Area in Aging Rats

    Science.gov (United States)

    Connor, Nadine P.; Russell, John A.; Wang, Hao; Jackson, Michelle A.; Mann, Laura; Kluender, Keith

    2009-01-01

    Purpose: Age-related changes in tongue function may contribute to dysphagia in elderly people. The authors' purpose was to investigate whether aged rats that have undergone tongue exercise would manifest increased protrusive tongue forces and increased genioglossus (GG) muscle fiber cross-sectional areas. Method: Forty-eight young adult,…

  5. Age and gender-specific reference values of orbital fat and muscle volumes in Caucasians

    NARCIS (Netherlands)

    Regensburg, N.I.; Wiersinga, W.M.; van Velthoven, M.E.J.; Berendschot, T.T.J.M.; Zonneveld, F.W.; Baldeschi, L.; Saeed, P.; Mourits, M.P.

    2011-01-01

    To provide age and gender-specific reference values for orbital fat and muscle volumes (MV) in Caucasian adults. Computed tomographic scans of 160 orbits from 52 men and 55 women, aged 20-80 years, not affected by orbital disease were evaluated. Orbital bony cavity volume (OV), fat volume (FV) and M

  6. Age and gender-specific reference values of orbital fat and muscle volumes in Caucasians

    NARCIS (Netherlands)

    Regensburg, N.I.; Wiersinga, W.M.; van Velthoven, M.E.J.; Berendschot, T.T.J.M.; Zonneveld, F.W.; Baldeschi, L.; Saeed, P.; Mourits, M.P.

    2011-01-01

    To provide age and gender-specific reference values for orbital fat and muscle volumes (MV) in Caucasian adults. Computed tomographic scans of 160 orbits from 52 men and 55 women, aged 20-80 years, not affected by orbital disease were evaluated. Orbital bony cavity volume (OV), fat volume (FV) and

  7. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy.

    Science.gov (United States)

    Buford, Thomas W; Anton, Stephen D; Judge, Andrew R; Marzetti, Emanuele; Wohlgemuth, Stephanie E; Carter, Christy S; Leeuwenburgh, Christiaan; Pahor, Marco; Manini, Todd M

    2010-10-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.

  8. Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth

    DEFF Research Database (Denmark)

    Farup, Jean; Rahbek, Stine Klejs; Riis, Simon

    2014-01-01

    -specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose......Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type......) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P

  9. Hyper-elastic properties of the human sternocleidomastoideus muscle in tension

    OpenAIRE

    Gras, Laure-Lise; MITTON, David; VIOT, Philippe; Laporte, Sébastien

    2012-01-01

    Numerical models of the human body require realistic mechanical properties of the muscles as input, but, generally, such data are available only for animals’ muscles. As a consequence, the aim of this study was to identify the hyper-elastic behavior of the human sternocleidomastoideus muscle in tension using different constitutive laws. Ten sternocleidomastoideus muscles were tested in vitro. The hyper-elastic behavior was modeled with an exponential law and a hyper-elastic constitutive...

  10. The effects of age and muscle contraction on AMPK activity and heterotrimer composition.

    Science.gov (United States)

    Hardman, Shalene E; Hall, Derrick E; Cabrera, Alyssa J; Hancock, Chad R; Thomson, David M

    2014-07-01

    Sarcopenia is characterized by increased skeletal muscle atrophy due in part to alterations in muscle metabolism. AMP-activated protein kinase (AMPK) is a master regulator of skeletal muscle metabolic pathways which regulate many cellular processes that are disrupted in old-age. Functional AMPK is a heterotrimer composed of α, β and γ subunits, and each subunit can be represented in the heterotrimer by one of two (α1/α2, β1/β2) or three (γ1/γ2/γ3) isoforms. Altered isoform composition affects AMPK localization and function. Previous work has shown that overall AMPK activation with endurance-type exercise is blunted in old vs. young skeletal muscle. However, details regarding the activation of the specific isoforms of AMPK, as well as the heterotrimeric composition of AMPK in old skeletal muscle, are unknown. Our purpose here, therefore, was to determine the effect of old-age on 1) the activation of the α1 and α2 catalytic subunits of AMPK in skeletal muscle by a continuous contraction bout, and 2) the heterotrimeric composition of skeletal muscle AMPK. We studied gastrocnemius (GAST) and tibialis anterior (TA) muscles from young adult (YA; 8months old) and old (O; 30months old) male Fischer344×Brown Norway F1 hybrid rats after an in situ bout of endurance-type contractions produced via electrical stimulation of the sciatic nerve (STIM). AMPKα phosphorylation and AMPKα1 and α2 activities were unaffected by age at rest. However, AMPKα phosphorylation and AMPKα2 protein content and activity were lower in O vs. YA after STIM. Conversely, AMPKα1 content was greater in O vs. YA muscle, and α1 activity increased with STIM in O but not YA muscles. AMPKγ3 overall concentration and its association with AMPKα1 and α2 were lower in O vs. YA GAST. We conclude that activation of AMPKα1 is enhanced, while activation of α2 is suppressed immediately after repeated skeletal muscle contractions in O vs. YA skeletal muscle. These changes are associated with

  11. Effect of postural angle on back muscle activities in aging female workers performing computer tasks.

    Science.gov (United States)

    Kamil, Nabilla Sofia Mohd; Dawal, Siti Zawiah Md

    2015-06-01

    [Purpose] This study investigated the effects of postural angle on back muscle activity during a computer task in aging women. [Subjects] Seventeen women ≥50 years old participated. [Methods] The participants were instructed to perform computer-related tasks for 20 minutes on a workstation that simulated typical office working conditions. Back posture was measured from the measured trunk and pelvic angles. Electromyography activities were recorded simultaneously from the cervical erector spinae, longissimus, and multifidus muscles. [Results] The lowest mean percentages of maximum voluntary contraction for the cervical erector spinae and longissimus muscles were obtained when the upper trunk and pelvic angles were between 0° to -5° from the sagittal plane. The back muscle activities increased as the upper trunk and pelvic angles exceeded 0°. Statistical analysis showed significant correlations between upper trunk angle and cervical erector spinae and longissimus muscle activities. Similarly, pelvic angle was significantly correlated with cervical erector spinae and multifidus muscle activities. [Conclusion] A neutral back posture minimizes muscle activities in aging women performing computer tasks.

  12. Gouty arthritis in the human aging process

    Directory of Open Access Journals (Sweden)

    Juliana Secchi Batista

    2012-09-01

    Full Text Available The aging process has gained universal recognition and is occurring at an accelerated pace. Gout is a metabolic disorder in which an overproduction and / or decreased excretion of uric acid, leading to the deposition of crystals of sodium monourato joints and soft tissue. The present study was based on a literature review that aimed to analyze the incidence of gouty arthritis in the human aging process. To this end, we searched for articles indexed journals, books, among others, published in English and Portuguese, using the keywords "Human Aging", "Rheumatic Diseases", "Drop" and "Gouty Arthritis". The data obtained suggest that the prevalence of gout is higher in men, affecting oligo / polyarticular inflammatory symptoms with smaller and often with involvement of small joints of the hands also may be the coexistence of gout with other autoimmune diseases such as ankylosing spondylitis and rheumatoid arthritis, should be performed nutritional treatment and medication.

  13. Age-related changes in consolidation of perceptual and muscle-based learning of motor skills

    OpenAIRE

    Rebecca M. C. Spencer; Pace-Schott, Edward F.

    2013-01-01

    Improvements in motor sequence learning come about via goal-based learning of the sequence of visual stimuli and muscle-based learning of the sequence of movement responses. In young adults, consolidation of goal-based learning is observed after intervals of sleep but not following wake, whereas consolidation of muscle-based learning is greater following intervals with wake compared to sleep. While the benefit of sleep on motor sequence learning has been shown to decline with age, how sleep c...

  14. Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Piil, Peter Bergmann; Egelund, Jon;

    2015-01-01

    regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed...... to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal...... in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age....

  15. Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Piil, Peter Bergmann; Egelund, Jon

    2015-01-01

    to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal......Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow...... regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed...

  16. Afferent contribution to locomotor muscle activity during unconstrained overground human walking: an analysis of triceps surae muscle fascicles.

    Science.gov (United States)

    af Klint, R; Cronin, N J; Ishikawa, M; Sinkjaer, T; Grey, M J

    2010-03-01

    Plantar flexor series elasticity can be used to dissociate muscle-fascicle and muscle-tendon behavior and thus afferent feedback during human walking. We used electromyography (EMG) and high-speed ultrasonography concomitantly to monitor muscle activity and muscle fascicle behavior in 19 healthy volunteers as they walked across a platform. On random trials, the platform was dropped (8 cm, 0.9 g acceleration) or held at a small inclination (up to +/-3 degrees in the parasagittal plane) with respect to level ground. Dropping the platform in the mid and late phases of stance produced a depression in the soleus muscle activity with an onset latency of about 50 ms. The reduction in ground reaction force also unloaded the plantar flexor muscles. The soleus muscle fascicles shortened with a minimum delay of 14 ms. Small variations in platform inclination produced significant changes in triceps surae muscle activity; EMG increased when stepping on an inclined surface and decreased when stepping on a declined surface. This sensory modulation of the locomotor output was concomitant with changes in triceps surae muscle fascicle and gastrocnemius tendon length. Assuming that afferent activity correlates to these mechanical changes, our results indicate that within-step sensory feedback from the plantar flexor muscles automatically adjusts muscle activity to compensate for small ground irregularities. The delayed onset of muscle fascicle movement after dropping the platform indicates that at least the initial part of the soleus depression is more likely mediated by a decrease in force feedback than length-sensitive feedback, indicating that force feedback contributes to the locomotor activity in human walking.

  17. Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice.

    Science.gov (United States)

    Leduc-Gaudet, Jean-Philippe; Picard, Martin; St-Jean Pelletier, Félix; Sgarioto, Nicolas; Auger, Marie-Joëlle; Vallée, Joanne; Robitaille, Richard; St-Pierre, David H; Gouspillou, Gilles

    2015-07-20

    Skeletal muscle aging is associated with a progressive decline in muscle mass and strength, a process termed sarcopenia. Evidence suggests that accumulation of mitochondrial dysfunction plays a causal role in sarcopenia, which could be triggered by impaired mitophagy. Mitochondrial function, mitophagy and mitochondrial morphology are interconnected aspects of mitochondrial biology, and may coordinately be altered with aging. However, mitochondrial morphology has remained challenging to characterize in muscle, and whether sarcopenia is associated with abnormal mitochondrial morphology remains unknown. Therefore, we assessed the morphology of SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria in skeletal muscle of young (8-12wk-old) and old (88-96wk-old) mice using a quantitative 2-dimensional transmission electron microscopy approach. We show that sarcopenia is associated with larger and less circular SS mitochondria. Likewise, aged IMF mitochondria were longer and more branched, suggesting increased fusion and/or decreased fission. Accordingly, although no difference in the content of proteins regulating mitochondrial dynamics (Mfn1, Mfn2, Opa1 and Drp1) was observed, a mitochondrial fusion index (Mfn2-to-Drp1 ratio) was significantly increased in aged muscles. Our results reveal that sarcopenia is associated with complex changes in mitochondrial morphology that could interfere with mitochondrial function and mitophagy, and thus contribute to aging-related accumulation of mitochondrial dysfunction and sarcopenia.

  18. DNA methylation and healthy human aging.

    Science.gov (United States)

    Jones, Meaghan J; Goodman, Sarah J; Kobor, Michael S

    2015-12-01

    The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies.

  19. Reversing Age Related Changes of the Laryngeal Muscles by Chronic Electrostimulation of the Recurrent Laryngeal Nerve

    Science.gov (United States)

    Karbiener, Michael; Jarvis, Jonathan C.; Perkins, Justin D.; Lanmüller, Hermann; Schmoll, Martin; Rode, Hanna S.; Gerstenberger, Claus; Gugatschka, Markus

    2016-01-01

    Age related atrophy of the laryngeal muscles -mainly the thyroarytenoid muscle (TAM)- leads to a glottal gap and consequently to a hoarse and dysphonic voice that significantly affects quality of life. The aim of our study was to reverse this atrophy by inducing muscular hypertrophy by unilateral functional electrical stimulation (FES) of the recurrent laryngeal nerve (RLN) in a large animal model using aged sheep (n = 5). Suitable stimulation parameters were determined by fatiguing experiments of the thyroarytenoid muscle in an acute trial. For the chronic trial an electrode was placed around the right RLN and stimulation was delivered once daily for 29 days. We chose a very conservative stimulation pattern, total stimulation time was two minutes per day, or 0.14% of total time. Overall, the mean muscle fiber diameter of the stimulated right TAM was significantly larger than the non-stimulated left TAM (30μm±1.1μm vs. 28μm±1.1 μm, p<0.001). There was no significant shift in fiber type distribution as judged by immunohistochemistry. The changes of fiber diameter could not be observed in the posterior cricoarytenoid muscle (PCAM). FES is a possible new treatment option for reversing the effects of age related laryngeal muscle atrophy. PMID:27893858

  20. Severely atrophic human muscle fibers with nuclear misplacement survive many years of permanent denervation

    Directory of Open Access Journals (Sweden)

    Ugo Carraro

    2016-06-01

    Full Text Available Likewise in rodents, after complete spinal cord injury (SCI the lower motor neuron (LMN denervated human muscle fibers lose completely the myofibrillar apparatus and the coil distribution of myonuclei that are relocated in groups (nuclear clumps in the center of severely atrophic muscle fibers. Up to two years of LMN denervation the muscle fibers with nuclear clumps are very seldom, but in this cohort of patients the severely atrophic muscle fibers are frequent in muscle biopsies harvested three to six years after SCI. Indeed, the percentage increased to 27 ± 9% (p< 0.001, and then abruptly decreased from the 6th year onward, when fibrosis takes over to neurogenic muscle atrophy. Immunohistochemical analyses shown that nuclear misplacements occurred in both fast and slow muscle fibers. In conclusion, human muscle fibers survive permanent denervation much longer than generally accepted and relocation of nuclei is a general behavior in long term denervated muscle fibers.

  1. Activity of upper limb muscles during human walking.

    Science.gov (United States)

    Kuhtz-Buschbeck, Johann P; Jing, Bo

    2012-04-01

    The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Substance P stimulation of cultured human smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Mitsuhashi, M.; Payan, D.G.

    1986-03-01

    Substance P (SP) has been shown to be mitogenic for cells active in the inflammatory response, such as lymphocytes and macrophages, and demonstrates vasodilatory and bronchoconstrictor properties, implicating SP receptor-mediated responses on smooth muscle cells. The effects of SP on cultured human vascular smooth muscle cell (HSMC) proliferative responses and protein synthesis were assessed by measuring the incorporation of (/sup 3/H)thymidine into DNA and (/sup 3/H)leucine into intracellular proteins, respectively. SP at concentrations of 10/sup -6/ to 10/sup -5/M stimulated a 40-50% increase in the incorporation of (/sup 3/H)thymidine in HMSC. In addition, the uptake of (/sup 3/H)leucine into HSMC proteins was increased significantly by SP over the concentration range 10/sup -11/ to 10/sup -6/M. Moreover, an enhancement of protein synthesis in HSMC by 10/sup -9/M SP was demonstrated by an increased incorporation of (/sup 35/S)methionine into cellular proteins of MW 40-30,000 daltons as assessed by autoradiographic analysis of HSMC lysates analyzed by SDS-PAGE. Furthermore, the uptake of (/sup 3/H)inositol into HSMC membrane phospholipid was increased significantly by SP in a dose-dependent manner over the concentration range 10/sup -11/ to 10/sup -6/M. Peptides such as SP which stimulate smooth muscle contraction, also demonstrate mitogenic properties on HSMC, suggesting that these cellular response shares common pathways of activation.

  3. Experimental neck muscle pain impairs standing balance in humans

    CERN Document Server

    Vuillerme, Nicolas; 10.1007/s00221-008-1639-7

    2009-01-01

    Impaired postural control has been reported in patients with chronic neck pain of both traumatic and non-traumatic etiologies, but whether painful stimulation of neck muscle per se can affect balance control during quiet standing in humans remains unclear. The purpose of the present experiment was thus to investigate the effect of experimental neck muscle pain on standing balance in young healthy adults. To achieve this goal, 16 male university students were asked to stand upright as still as possible on a force platform with their eyes closed in two conditions of No pain and Pain of the neck muscles elicited by experimental painful electrical stimulation. Postural control and postural performance were assessed by the displacements of the center of foot pressure (CoP) and of the center of mass (CoM), respectively. The results showed increased CoP and CoM displacements variance, range, mean velocity, and mean and median frequencies in the Pain relative to the No pain condition. The present findings emphasize t...

  4. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Deshmukh, Atul; Long, Yun Chau

    2007-01-01

    suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were...... incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P ... exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure....

  5. Effects of age and regular exercise on muscle strength and endurance.

    Science.gov (United States)

    Laforest, S; St-Pierre, D M; Cyr, J; Gayton, D

    1990-01-01

    Twenty male and 20 female non-professional tennis players were classified into two different age groups (n = 10 per group): young active men (30.4 +/- 3.3 years), young active women (27.5 +/- 4.3 years), elderly active men (64.4 +/- 3.7 years), and elderly active women (65.3 +/- 4.5 years). These individuals were matched (n = 10 per group) according to sex, age, height and mass to sedentary individuals of the same socio-economical background: young sedentary men (29.2 +/- 3.4 years), young sedentary women (25.6 +/- 4.4 years), elderly sedentary men (65.2 +/- 3.2 years) and elderly sedentary women (65.6 +/- 4.4 years). An isokinetic dynamometer was used to measure the strength of the knee extensors and flexors (two separate occasions) and the endurance of the extensors. Vastus lateralis electromyogram (EMG) was measured concomitantly. Significant sex, age and exercise effects (P less than 0.001) were observed for peak torque of both muscle groups. The effect of age on extensor strength was more pronounced at high speeds where men were also able to generate larger relative torques than women. No age or sex effects were noted for muscle endurance. However, muscles of active individuals demonstrated a greater resistance to fatigue than those of sedentary individuals. In conclusion, men were found to be stronger than women, age was associated with a decrease in muscle strength, but not of muscle endurance, and tennis players were stronger and had muscles that were more resistant to fatigue than their sedentary pairs in both age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. MicroRNA-34a Induces Vascular Smooth Muscle Cells Senescence by SIRT1 Downregulation and Promotes the Expression of Age-Associated Pro-inflammatory Secretory Factors.

    Science.gov (United States)

    Badi, Ileana; Burba, Ilaria; Ruggeri, Clarissa; Zeni, Filippo; Bertolotti, Matteo; Scopece, Alessandro; Pompilio, Giulio; Raucci, Angela

    2015-11-01

    Arterial aging is a major risk factor for the occurrence of cardiovascular diseases. The aged artery is characterized by endothelial dysfunction and vascular smooth muscle cells altered physiology together with low-grade chronic inflammation. MicroRNA-34a (miR-34a) has been recently implicated in cardiac, endothelial, and endothelial progenitor cell senescence; however, its contribution to aging-associated vascular smooth muscle cells phenotype has not been explored so far. We found that miR-34a was highly expressed in aortas isolated from old mice. Moreover, its well-known target, the longevity-associated protein SIRT1, was significantly downregulated during aging in both endothelial cells and vascular smooth muscle cells. Increased miR-34a as well as decreased SIRT1 expression was also observed in replicative-senescent human aortic smooth muscle cells. miR-34a overexpression in proliferative human aortic smooth muscle cells caused cell cycle arrest along with enhanced p21 protein levels and evidence of cell senescence. Furthermore, miR-34a ectopic expression induced pro-inflammatory senescence-associated secretory phenotype molecules. Finally, SIRT1 protein significantly decreased upon miR-34a overexpression and restoration of its levels rescued miR-34a-dependent human aortic smooth muscle cells senescence, but not senescence-associated secretory phenotype factors upregulation. Taken together, our findings suggest that aging-associated increase of miR-34a expression levels, by promoting vascular smooth muscle cells senescence and inflammation through SIRT1 downregulation and senescence-associated secretory phenotype factors induction, respectively, may lead to arterial dysfunctions.

  7. Stretch reflex instability compared in three different human muscles.

    Science.gov (United States)

    Durbaba, R; Taylor, A; Manu, C A; Buonajuti, M

    2005-06-01

    The possibility of causing instability in the stretch reflex has been examined in three different human muscles: biceps, first dorsal interosseous (FDI) of the hand and digastric. Tremor recorded as fluctuation of isometric force was compared with that occurring during contraction against a spring load. The spring compliance was selected to make the natural frequency of the part in each case appropriate for oscillations in the short latency stretch reflex. A computer model of the whole system was used to predict the frequency at which oscillations should be expected and to estimate the reflex gain required in each case to cause sustained oscillations. Estimates were computed of the autospectra of the force records and of the rectified surface EMG signals and of the coherence functions. Normal subjects showed no evidence of a distinct spectral peak during isometric recording from any of the three muscles. However, in anisometric conditions regular oscillations in force occurred in biceps, but not in FDI or digastric. The oscillations in biceps at 8-9 Hz were accompanied by similar oscillations in the EMG which were highly coherent with the force signal. The results are consistent with the presence of a strong segmental stretch reflex effect in biceps and weak or absent reflex in FDI. Digastric is known to contain no muscle spindles and therefore to lack a stretch reflex. In two subjects who volunteered that they had more tremor than normal, but had no known neurological abnormality, there was a distinct peak in the force spectrum at 8-9 Hz in biceps and FDI in isometric conditions with coherent EMG activity. The peak increased in size in anisometric conditions in biceps but not in FDI. This component appears to be of central rather than of reflex origin. No equivalent component was found in digastric records. The results are discussed in relation to the possible role of the short latency stretch reflex in the genesis of physiological tremor in different muscles.

  8. On the mechanism by which dietary nitrate improves human skeletal muscle function

    Directory of Open Access Journals (Sweden)

    Charles eAffourtit

    2015-07-01

    Full Text Available Inorganic nitrate is present at high levels in beetroot and celery, and in green leafy vegetables such as spinach and lettuce. Though long believed inert, nitrate can be reduced to nitrite in the human mouth and, further, under hypoxia and/or low pH, to nitric oxide. Dietary nitrate has thus been associated favourably with nitric-oxide-regulated processes including blood flow and energy metabolism. Indeed, the therapeutic potential of dietary nitrate in cardiovascular disease and metabolic syndrome – both ageing-related medical disorders – has attracted considerable recent research interest. We and others have shown that dietary nitrate supplementation lowers the oxygen cost of human exercise, as less respiratory activity appears to be required for a set rate of skeletal muscle work. This striking observation predicts that nitrate benefits the energy metabolism of human muscle, increasing the efficiency of either mitochondrial ATP synthesis and/or of cellular ATP-consuming processes. In this mini-review, we evaluate experimental support for the dietary nitrate effects on muscle bioenergetics and we critically discuss the likelihood of nitric oxide as the molecular mediator of such effects.

  9. Postmortem muscle protein degradation in humans as a tool for PMI delimitation.

    Science.gov (United States)

    Pittner, Stefan; Ehrenfellner, Bianca; Monticelli, Fabio C; Zissler, Angela; Sänger, Alexandra M; Stoiber, Walter; Steinbacher, Peter

    2016-11-01

    Forensic estimation of time since death relies on diverse approaches, including measurement and comparison of environmental and body core temperature and analysis of insect colonization on a dead body. However, most of the applied methods have practical limitations or provide insufficient results under certain circumstances. Thus, new methods that can easily be implemented into forensic routine work are required to deliver more and discrete information about the postmortem interval (PMI). Following a previous work on skeletal muscle degradation in the porcine model, we analyzed human postmortem skeletal muscle samples of 40 forensic cases by Western blotting and casein zymography. Our results demonstrate predictable protein degradation processes in human muscle that are distinctly associated with temperature and the PMI. We provide information on promising degradation markers for certain periods of time postmortem, which can be useful tools for time since death delimitation. In addition, we discuss external influencing factors such as age, body mass index, sex, and cause of death that need to be considered in future routine application of the method in humans.

  10. The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun [Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Zheng, Timothy S.; Burkly, Linda C. [Department of Immunology, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142 (United States); Kumar, Ashok, E-mail: ashok.kumar@louisville.edu [Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202 (United States)

    2014-04-18

    Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways.

  11. Ursolic acid ameliorates aging-metabolic phenotype through promoting of skeletal muscle rejuvenation.

    Science.gov (United States)

    Bakhtiari, Nuredin; Hosseinkhani, Saman; Tashakor, Amin; Hemmati, Roohullah

    2015-07-01

    Ursolic acid (UA) is a lipophilic compound, which highly found in apple peels. UA has some certain features, of the most important is its anabolic effects on skeletal muscles, which in turn plays a prominent role in the aging process, encouraged us to evaluate skeletal muscle rejuvenation. This study seeks to address the two following questions: primarily, we wonder to know if UA increases anti-aging biomarkers (SIRT1 and PGC-1α) in the isolated satellite cells, to pave the way for satellite cells proliferation. The results revealed that UA elevated the expression of SIRT1 (∼ 35 folds) and PGC-1α (∼ 175 folds) genes. The other question that needs to be asked, however, is to understand whether it is possible to generalize the in vitro findings to in vivo. For this, a study was designed to investigate the effects of UA on the cellular energy status in the animal models (C57BL/6 mice). We found that UA decreased cellular energy charges such as ATP (∼ 3 times) and ADP (∼ 18 times). With respect to the role of UA in energy expenditure and as an anti-aging biomarker, one might wonder to elucidate skeletal muscle rejuvenation as well as satellite cells proliferation and neomyogenesis. The results illustrated that UA boosted neomyogenesis through enhancing the number of satellite cells. In addition, rejuvenation effects of UA on the skeletal muscle promptly encouraged us to reexamine the performance of skeletal muscles. The results indicated that UA through increasing myoglobin expression (∼ 2 folds) accompanied with transforming of glycolytic to fast oxidative status chiefly and slow-twitch muscle fibers. To the best of our knowledge, it seems that UA might be considered as a potential candidate for treatment of pathological conditions associated with muscular atrophy and dysfunction, including skeletal muscle atrophy, amyotrophic lateral sclerosis (ALS), sarcopenia and metabolic diseases of the muscles.

  12. Sparing of extraocular muscle in aging and muscular dystrophies: A myogenic precursor cell hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Kallestad, Kristen M.; Hebert, Sadie L.; McDonald, Abby A.; Daniel, Mark L.; Cu, Sharon R.; McLoon, Linda K., E-mail: mcloo001@tc.umn.edu

    2011-04-01

    The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a population of activated satellite cells even in aging. These data suggested the hypothesis that there is a population of myogenic precursor cells (mpcs) in EOM that is different from those in limb, with either elevated numbers of stem cells and/or mpcs with superior proliferative capacity compared to mpcs in limb. Using flow cytometry, EOM and limb muscle mononuclear cells were compared, and a number of differences were seen. Using two different cell isolation methods, EOM have significantly more mpcs per mg muscle than limb skeletal muscle. One specific subpopulation significantly increased in EOM compared to limb was positive for CD34 and negative for Sca-1, M-cadherin, CD31, and CD45. We named these the EOMCD34 cells. Similar percentages of EOMCD34 cells were present in both newborn EOM and limb muscle. They were retained in aged EOM, whereas the population decreased significantly in adult limb muscle and were extremely scarce in aged limb muscle. Most importantly, the percentage of EOMCD34 cells was elevated in the EOM from both the mdx and the mdx/utrophin{sup -/-} (DKO) mouse models of DMD and extremely scarce in the limb muscles of these mice. In vitro, the EOMCD34 cells had myogenic potential, forming myotubes in differentiation media. After determining a media better able to induce proliferation in these cells, a fusion index was calculated. The cells isolated from EOM had a 40% higher fusion index compared to the same cells isolated from limb muscle. The EOMCD34 cells were resistant to both oxidative stress and mechanical injury. These data support our hypothesis that the EOM may be spared in aging and in muscular dystrophies due to a

  13. Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis.

    Science.gov (United States)

    Kallestad, Kristen M; Hebert, Sadie L; McDonald, Abby A; Daniel, Mark L; Cu, Sharon R; McLoon, Linda K

    2011-04-01

    The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a population of activated satellite cells even in aging. These data suggested the hypothesis that there is a population of myogenic precursor cells (mpcs) in EOM that is different from those in limb, with either elevated numbers of stem cells and/or mpcs with superior proliferative capacity compared to mpcs in limb. Using flow cytometry, EOM and limb muscle mononuclear cells were compared, and a number of differences were seen. Using two different cell isolation methods, EOM have significantly more mpcs per mg muscle than limb skeletal muscle. One specific subpopulation significantly increased in EOM compared to limb was positive for CD34 and negative for Sca-1, M-cadherin, CD31, and CD45. We named these the EOMCD34 cells. Similar percentages of EOMCD34 cells were present in both newborn EOM and limb muscle. They were retained in aged EOM, whereas the population decreased significantly in adult limb muscle and were extremely scarce in aged limb muscle. Most importantly, the percentage of EOMCD34 cells was elevated in the EOM from both the mdx and the mdx/utrophin(-/-) (DKO) mouse models of DMD and extremely scarce in the limb muscles of these mice. In vitro, the EOMCD34 cells had myogenic potential, forming myotubes in differentiation media. After determining a media better able to induce proliferation in these cells, a fusion index was calculated. The cells isolated from EOM had a 40% higher fusion index compared to the same cells isolated from limb muscle. The EOMCD34 cells were resistant to both oxidative stress and mechanical injury. These data support our hypothesis that the EOM may be spared in aging and in muscular dystrophies due to a subpopulation

  14. Influence of knee flexion angle and age on triceps surae muscle fatigue during heel raises.

    Science.gov (United States)

    Hébert-Losier, Kim; Schneiders, Anthony G; García, José A; Sullivan, S John; Simoneau, Guy G

    2012-11-01

    The triceps surae (TS) muscle-tendon unit is 1 of the most commonly injured in elite and recreational athletes, with a high prevalence in middle-aged adults. The performance of maximal numbers of unilateral heel raises is used to assess, train, and rehabilitate TS endurance and conventionally prescribed in 0° knee flexion (KF) for the gastrocnemius and 45° for the soleus (SOL). However, the extent of muscle selectivity conferred through the change in the knee angle is lacking for heel raises performed to volitional fatigue. This study investigated the influence of knee angle on TS muscle fatigue during heel raises and determined whether fatigue differed between middle-aged and younger-aged adults. Forty-eight healthy individuals aged 18-25 and 35-45 years performed maximal numbers of unilateral heel raises in 0° and 45° KF. Median frequencies and linear regression slopes were calculated from the SOL, gastrocnemius medialis (GM), and gastrocnemius lateralis (GL) surface electromyographic signals. Stepwise mixed-effect regressions were used for analysis. The subjects completed an average of 45 and 48 heel raises in 0° and 45° KF, respectively. The results indicated that the 3 muscles fatigued during testing as all median frequencies decreased, and regression slopes were negative. Consistent with muscle physiology and fiber typing, fatigue was greater in the GM and GL than in the SOL (p < 0.001). However, knee angle did not influence TS muscle fatigue parameters (p = 0.814), with similar SOL, GM, and GL fatigue in 0° and 45° KF. These findings are in contrast with the traditionally described clinical use of heel raises in select knee angles for the gastrocnemius and the SOL. Furthermore, no difference in TS fatigue between the 2 age groups was able to be determined, despite the reported higher prevalence of injury in middle-aged individuals.

  15. Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

    DEFF Research Database (Denmark)

    Lundby, Carsten; Hellsten, Ylva; Jensen, Mie B. F.;

    2008-01-01

    The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study...... the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects...... (n = 11) received a single Epo injection of 15,000 IU (double blinded, cross over, placebo). A single Epo injection reduced myoglobin and increased transferrin receptor and MRF-4 mRNA content within 10 h after injection. Plasma hormones remained unaltered. Capillarization and fiber hypertrophy...

  16. Overexpression of the mitochondrial T3 receptor induces skeletal muscle atrophy during aging.

    Directory of Open Access Journals (Sweden)

    François Casas

    Full Text Available In previous studies, we characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43 acting as a mitochondrial transcription factor. In in vitro and in vivo studies, we have shown that p43 increases mitochondrial transcription and mitochondrial biogenesis. In addition, p43 overexpression in skeletal muscle stimulates mitochondrial respiration and induces a shift in metabolic and contractile features of muscle fibers which became more oxidative.Here we have studied the influence of p43 overexpression in skeletal muscle of mice during aging. We report that p43 overexpression initially increased mitochondrial mass. However, after the early rise in mitochondrial DNA occurring at 2 months of age in transgenic mice, we observed a progressive decrease of mitochondrial DNA content which became 2-fold lower at 23 months of age relatively to control animals. Moreover, p43 overexpression induced an oxidative stress characterized by a strong increase of lipid peroxidation and protein oxidation in quadriceps muscle, although antioxidant enzyme activities (catalase and superoxide dismutase were stimulated. In addition, muscle atrophy became detectable at 6 months of age, probably through a stimulation of the ubiquitin proteasome pathway via two muscle-specific ubiquitin ligases E3, Atrogin-1/MAFbx and MuRF1.Taken together, these results demonstrate that a prolonged stimulation of mitochondrial activity induces muscle atrophy. In addition, these data underline the importance of a tight control of p43 expression and suggest that a deregulation of the direct T3 mitochondrial pathway could be one of the parameters involved in the occurrence of sarcopenia.

  17. Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat.

    Directory of Open Access Journals (Sweden)

    Mitsunori Miyazaki

    Full Text Available It is well known that spontaneously hypertensive rats (SHR develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007 linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including Mck, Ttn and Mef2c. We next performed circadian time-course collections at a young age (8 weeks; pre-hypertensive and adult age (22 weeks; hypertensive to determine if clock gene expression was disrupted in gastrocnemius, heart and liver tissues prior to or after the rats became hypertensive. We found that hypertensive/hypertrophic SHR showed a dampening of peak Bmal1 and Rev-erb expression in the liver, and the clock-controlled gene Pgc1α in the gastrocnemius. In addition, the core-clock gene Clock and the muscle-specific, clock-controlled gene Myod1, no longer maintained a circadian pattern of expression in gastrocnemius from the hypertensive SHR. These findings provide a framework to suggest a mechanism whereby chronic heart failure leads to skeletal muscle pathologies; prolonged dysregulation of the molecular clock in skeletal muscle results in altered Clock, Pgc1α and Myod1 expression which in turn leads to the mis-regulation of target genes important for mechanical and metabolic function of skeletal muscle.

  18. Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat.

    Science.gov (United States)

    Miyazaki, Mitsunori; Schroder, Elizabeth; Edelmann, Stephanie E; Hughes, Michael E; Kornacker, Karl; Balke, C William; Esser, Karyn A

    2011-01-01

    It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including Mck, Ttn and Mef2c. We next performed circadian time-course collections at a young age (8 weeks; pre-hypertensive) and adult age (22 weeks; hypertensive) to determine if clock gene expression was disrupted in gastrocnemius, heart and liver tissues prior to or after the rats became hypertensive. We found that hypertensive/hypertrophic SHR showed a dampening of peak Bmal1 and Rev-erb expression in the liver, and the clock-controlled gene Pgc1α in the gastrocnemius. In addition, the core-clock gene Clock and the muscle-specific, clock-controlled gene Myod1, no longer maintained a circadian pattern of expression in gastrocnemius from the hypertensive SHR. These findings provide a framework to suggest a mechanism whereby chronic heart failure leads to skeletal muscle pathologies; prolonged dysregulation of the molecular clock in skeletal muscle results in altered Clock, Pgc1α and Myod1 expression which in turn leads to the mis-regulation of target genes important for mechanical and metabolic function of skeletal muscle.

  19. Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals.

    Science.gov (United States)

    Schwörer, Simon; Becker, Friedrich; Feller, Christian; Baig, Ali H; Köber, Ute; Henze, Henriette; Kraus, Johann M; Xin, Beibei; Lechel, André; Lipka, Daniel B; Varghese, Christy S; Schmidt, Manuel; Rohs, Remo; Aebersold, Ruedi; Medina, Kay L; Kestler, Hans A; Neri, Francesco; von Maltzahn, Julia; Tümpel, Stefan; Rudolph, K Lenhard

    2016-12-15

    The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGFβ, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.

  20. Age-related differences in Achilles tendon properties and triceps surae muscle architecture in vivo.

    Science.gov (United States)

    Stenroth, Lauri; Peltonen, Jussi; Cronin, Neil J; Sipilä, Sarianna; Finni, Taija

    2012-11-01

    This study examined the concurrent age-related differences in muscle and tendon structure and properties. Achilles tendon morphology and mechanical properties and triceps surae muscle architecture were measured from 100 subjects [33 young (24 ± 2 yr) and 67 old (75 ± 3 yr)]. Motion analysis-assisted ultrasonography was used to determine tendon stiffness, Young's modulus, and hysteresis during isometric ramp contractions. Ultrasonography was used to measure muscle architectural features and size and tendon cross-sectional area. Older participants had 17% lower (P Triceps surae muscle size was smaller (P < 0.05) and gastrocnemius medialis muscle fascicle length shorter (P < 0.05) in old compared with young. Maximal plantarflexion force was associated with tendon stiffness and Young's modulus (r = 0.580, P < 0.001 and r = 0.561, P < 0.001, respectively). Comparison between old and young subjects with similar strengths did not reveal a difference in tendon stiffness. The results suggest that regardless of age, Achilles tendon mechanical properties adapt to match the level of muscle performance. Old people may compensate for lower tendon material properties by increasing tendon cross-sectional area. Lower tendon stiffness in older subjects might be beneficial for movement economy in low-intensity locomotion and thus optimized for their daily activities.

  1. Effects of lubiprostone on human uterine smooth muscle cells.

    Science.gov (United States)

    Cuppoletti, John; Malinowska, Danuta H; Chakrabarti, Jayati; Ueno, Ryuji

    2008-06-01

    Lubiprostone, a bicyclic fatty acid derivative and member of a new class of compounds called prostones, locally activates ClC-2 Cl(-) channels without activation of prostaglandin receptors. The present study was specifically designed to test and compare lubiprostone and prostaglandin effects at the cellular level using human uterine smooth muscle cells. Effects on [Ca(2+)](i), membrane potential and [cAMP](i) in human uterine smooth muscle cells were measured. 10 nM lubiprostone significantly decreased [Ca(2+)](i) from 188 to 27 nM, which was unaffected by 100 nM SC-51322, a prostaglandin EP receptor antagonist. In contrast 10nM PGE(2) and PGE(1) both increased [Ca(2+)](i) 3-5-fold which was blocked by SC-51322. Similarly, lubiprostone and prostaglandins had opposite/different effects on membrane potential and [cAMP](i). Lubiprostone caused SC-51322-insensitive membrane hyperpolarization and no effect on [cAMP](i). PGE(2) and PGE(1) both caused SC-51322-sensitive membrane depolarization and increased [cAMP](i). Lubiprostone has fundamentally different cellular effects from prostaglandins that are not mediated by EP receptors.

  2. Resistance exercise and the mechanisms of muscle mass regulation in humans: acute effects on muscle protein turnover and the gaps in our understanding of chronic resistance exercise training adaptation.

    Science.gov (United States)

    Murton, A J; Greenhaff, P L

    2013-10-01

    Increasing muscle mass is important when attempting to maximize sports performance and achieve physique augmentation. However, the preservation of muscle mass is essential to maintaining mobility and quality of life with aging, and also impacts on our capacity to recover from illness. Nevertheless, our understanding of the processes that regulate muscle mass in humans during resistance exercise training, chronic disuse and rehabilitation training following atrophy remains very unclear. Here, we report on some of the recent developments in the study of those processes thought to be responsible for governing human muscle protein turnover in response to intense physical activity. Specifically, the effects of acute and chronic resistance exercise in healthy volunteers and also in response to rehabilitation resistance exercise training following muscle atrophy will be discussed, with discrepancies and gaps in our understanding highlighted. In particular, ubiquitin-proteasome mediated muscle proteolysis (Muscle Atrophy F-box/Atrogin-1 and Muscle RING Finger 1), translation initiation of muscle protein synthesis (mammalian target of rapamycin signaling), and satellite cell mediated myogenesis are highlighted as pathways of special relevance to muscle protein metabolism in response to acute resistance exercise. Furthermore, research focused on quantifying signaling and molecular events that modulate muscle protein synthesis and protein degradation under conditions of chronic resistance training is highlighted as being urgently needed to improve knowledge gaps. These studies need to include multiple time-point measurements over the course of any training intervention and must include dynamic measurements of muscle protein synthesis and degradation and sensitive measures of muscle mass. This article is part of a Directed Issue entitled Molecular basis of muscle wasting.

  3. Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise.

    Science.gov (United States)

    Pilegaard, Henriette; Osada, Takuya; Andersen, Lisbeth T; Helge, Jørn W; Saltin, Bengt; Neufer, P Darrell

    2005-08-01

    In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabolic genes during recovery from exercise, 9 male subjects (aged 22-27) completed 75 minutes of cycling exercise at 75% Vo2 max on 2 occasions, consuming either a high-carbohydrate (HC) or low-carbohydrate (LC) diet during the subsequent 24 hours of recovery. Nuclei were isolated and tissue frozen from vastus lateralis muscle biopsies obtained before exercise and 2, 5, 8, and 24 hours after exercise. Muscle glycogen was restored to near resting levels within 5 hours in the HC trial, but remained depressed through 24 hours in the LC trial. During the 2- to 8-hour recovery period, leg glucose uptake was 5- to 15-fold higher with HC ingestion, whereas arterial plasma free fatty acid levels were approximately 3- to 7-fold higher with LC ingestion. Exercise increased (P < .05) transcription and/or mRNA content of the pyruvate dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, carnitine palmitoyltransferase I, hexokinase II, peroxisome proliferator activated receptor gamma coactivator-1 alpha, and peroxisome proliferator activated receptor alpha. Providing HC during recovery reversed the activation of pyruvate dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, and carnitine palmitoyltransferase I within 5 to 8 hours after exercise, whereas providing LC during recovery elicited a sustained/enhanced increase in activation of these genes through 8 to 24 hours of recovery. These findings provide evidence that factors associated with substrate availability and/or cellular metabolic recovery (eg, muscle glycogen restoration) influence the transcriptional regulation of metabolic genes in skeletal muscle of humans during recovery from exercise.

  4. Visualization and quantitation of GLUT4 translocation in human skeletal muscle following glucose ingestion and exercise.

    Science.gov (United States)

    Bradley, Helen; Shaw, Christopher S; Bendtsen, Claus; Worthington, Philip L; Wilson, Oliver J; Strauss, Juliette A; Wallis, Gareth A; Turner, Alice M; Wagenmakers, Anton J M

    2015-05-11

    Insulin- and contraction-stimulated increases in glucose uptake into skeletal muscle occur in part as a result of the translocation of glucose transporter 4 (GLUT4) from intracellular stores to the plasma membrane (PM). This study aimed to use immunofluorescence microscopy in human skeletal muscle to quantify GLUT4 redistribution from intracellular stores to the PM in response to glucose feeding and exercise. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of ten insulin-sensitive men in the basal state and following 30 min of cycling exercise (65% VO2 max). Muscle biopsy samples were also taken from a second cohort of ten age-, BMI- and VO2 max-matched insulin-sensitive men in the basal state and 30 and 60 min following glucose feeding (75 g glucose). GLUT4 and dystrophin colocalization, measured using the Pearson's correlation coefficient, was increased following 30 min of cycling exercise (baseline r = 0.47 ± 0.01; post exercise r = 0.58 ± 0.02; P GLUT4 clusters were partially depleted following 30 min cycling exercise, but not 30 min after glucose feeding. This study has, for the first time, used immunofluorescence microscopy in human skeletal muscle to quantify increases in GLUT4 and dystrophin colocalization and depletion of GLUT4 from large and smaller clusters as evidence of net GLUT4 translocation to the PM.

  5. Dynamic proteome profiling of individual proteins in human skeletal muscle after a high-fat diet and resistance exercise.

    Science.gov (United States)

    Camera, Donny M; Burniston, Jatin G; Pogson, Mark A; Smiles, William J; Hawley, John A

    2017-08-30

    It is generally accepted that muscle adaptation to resistance exercise (REX) training is underpinned by contraction-induced, increased rates of protein synthesis and dietary protein availability. By using dynamic proteome profiling (DPP), we investigated the contribution of both synthesis and breakdown to changes in abundance on a protein-by-protein basis in human skeletal muscle. Age-matched, overweight males consumed 9 d of a high-fat, low-carbohydrate diet during which time they either undertook 3 sessions of REX or performed no exercise. Precursor enrichment and the rate of incorporation of deuterium oxide into newly synthesized muscle proteins were determined by mass spectrometry. Ninety proteins were included in the DPP, with 28 proteins exhibiting significant responses to REX. The most common pattern of response was an increase in turnover, followed by an increase in abundance with no detectable increase in protein synthesis. Here, we provide novel evidence that demonstrates that the contribution of synthesis and breakdown to changes in protein abundance induced by REX differ on a protein-by-protein basis. We also highlight the importance of the degradation of individual muscle proteins after exercise in human skeletal muscle.-Camera, D. M., Burniston, J. G., Pogson, M. A., Smiles, W. J., Hawley, J. A. Dynamic proteome profiling of individual proteins in human skeletal muscle after a high-fat diet and resistance exercise. © FASEB.

  6. Therapeutic isolation and expansion of human skeletal muscle-derived stem cells for the use of muscle-nerve-blood vessel reconstitution

    Directory of Open Access Journals (Sweden)

    Tetsuro eTamaki

    2015-06-01

    Full Text Available Skeletal muscle makes up 40-50% of body mass, and is thus considered to be a good adult stem cell source for autologous therapy. Although, several stem/progenitor cells have been fractionated from mouse skeletal muscle showing a high potential for therapeutic use, it is unclear whether this is the case in human. Differentiation and therapeutic potential of human skeletal muscle-derived cells (Sk-Cs was examined. Samples (5-10 g were obtained from the abdominal and leg muscles of 36 patients (age, 17-79 years undergoing prostate cancer treatment or leg amputation surgery. All patients gave informed consent. Sk-Cs were isolated using conditioned collagenase solution, and were then sorted as CD34-/CD45-/CD29+ (Sk-DN/29+ and CD34+/CD45- (Sk-34 cells, in a similar manner as for the previous mouse Sk-Cs. Both cell fractions were appropriately expanded using conditioned culture medium for about 2 weeks. Differentiation potentials were then examined during cell culture and in vivo transplantation into the severely damaged muscles of athymic nude mice and rats. Interestingly, these two cell fractions could be divided into highly myogenic (Sk-DN/29+ and multipotent stem cell (Sk-34 fractions, in contrast to mouse Sk-Cs, which showed comparable capacities in both cells. At 6 weeks after the separate transplantation of both cell fractions, the former showed an active contribution to muscle fiber regeneration, but the latter showed vigorous engraftment to the interstitium associated with differentiation into Schwann cells, perineurial/endoneurial cells, and vascular endothelial cells and pericytes, which corresponded to previous observations with mouse SK-Cs. Importantly, mixed cultures of both cells resulted the reduction of tissue reconstitution capacities in vivo, whereas co-transplantation after separate expansion showed favorable results. Therefore, human Sk-Cs are potentially applicable to therapeutic autografts and show multiple differentiation

  7. Stretch-shortening cycle muscle power in women and men aged 18-81 years

    DEFF Research Database (Denmark)

    Edwén, C E; Thorlund, Jonas Bloch; Magnusson, Stig Peter;

    2014-01-01

    This study explored the age-related deterioration in stretch-shortening cycle (SSC) muscle power and concurrent force-velocity properties in women and men across the adult life span. A total of 315 participants (women: n = 188; men: n = 127) aged 18-81 years performed maximal countermovement jump...... on an instrumented force plate. Maximal SSC leg extension power expressed per kg body mass (Ppeak) was greater in men than in women across the adult age span (P ......This study explored the age-related deterioration in stretch-shortening cycle (SSC) muscle power and concurrent force-velocity properties in women and men across the adult life span. A total of 315 participants (women: n = 188; men: n = 127) aged 18-81 years performed maximal countermovement jumps...

  8. Effect of aging on performance, muscle activation and perceived stress during mentally demanding computer tasks

    DEFF Research Database (Denmark)

    Alkjaer, Tine; Pilegaard, Marianne; Bakke, Merete

    2005-01-01

    OBJECTIVES: This study examined the effects of age on performance, muscle activation, and perceived stress during computer tasks with different levels of mental demand. METHODS: Fifteen young and thirteen elderly women performed two computer tasks [color word test and reference task] with different...... demands affect young and elderly women differently. Thus the mentally demanding computer task had a more pronounced effect on the elderly than on the young. In contrast to the results in the reference task, the same level of muscle activity for most muscles and the same level of self-reported difficulty...... levels of mental demand but similar physical demands. The performance (clicking frequency, percentage of correct answers, and response time for correct answers) and electromyography from the forearm, shoulder, and neck muscles were recorded. Visual analogue scales were used to measure the participants...

  9. Physical activity as intervention for age-related loss of muscle mass and function

    DEFF Research Database (Denmark)

    Eriksen, Christian Skou; Garde, Ellen; Reislev, Nina Linde

    2016-01-01

    to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative......INTRODUCTION: Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known...... and cognitive function, mental well-being, health-related quality of life and brain morphology. METHODS AND ANALYSIS: The study includes 450 home-dwelling men and women (62-70 years). Participants are randomly allocated to (1) 1 year of supervised, centre-based heavy resistance training, (2) home-based moderate...

  10. Biomarkers related to aging in human populations.

    Science.gov (United States)

    Crimmins, Eileen; Vasunilashorn, Sarinnapha; Kim, Jung Ki; Alley, Dawn

    2008-01-01

    Biomarkers are increasingly employed in empirical studies of human populations to understand physiological processes that change with age, diseases whose onset appears linked to age, and the aging process itself. In this chapter, we describe some of the most commonly used biomarkers in population aging research, including their collection, associations with other markers, and relationships to health outcomes. We discuss biomarkers of the cardiovascular system, metabolic processes, inflammation, activity in the hypothalamic-pituitary axis (HPA) and sympathetic nervous system (SNS), and organ functioning (including kidney, lung, and heart). In addition, we note that markers of functioning of the central nervous system and genetic markers are now becoming part of population measurement. Where possible, we detail interrelationships between these markers by providing correlations between high risk levels of each marker from three population-based surveys: the National Health and Nutrition Examination Survey (NHANES) III, NHANES 1999-2002, and the MacArthur Study of Successful Aging. NHANES III is used instead of NHANES 1999-2002 when specific markers of interest are available only in NHANES III and when we examine the relationship of biomarkers to mortality which is only known for NHANES III. We also describe summary measures combining biomarkers across systems. Finally, we examine associations between individual markers and mortality and provide information about biomarkers of growing interest for future research in population aging and health.

  11. Popeye proteins: muscle for the aging sinus node.

    Science.gov (United States)

    Boukens, Bastiaan J; Christoffels, Vincent M

    2012-03-01

    The electrical impulses that dictate the rhythm of the heartbeat in normal situations and during exercise or stress are initiated by a small number of sinus node pacemaker cells. Senescence and dysfunction of the sinus node affects many people later in life, causing physiologically inappropriate heart rates, but the underlying mechanisms are not well understood. In this issue of the JCI, Froese and colleagues show that deficiency in either Popeye domain containing 1 (Popdc1) or Popdc2 leads to sinus node dysfunction under stressed conditions in aged mice. The mechanism reported to underlie the effects of Popdc1/2 deficiency in mice may cause the stress-induced sinus node dysfunction found in many aged individuals and may point to new strategies for therapeutic intervention.

  12. Series elasticity of the human triceps surae muscle : Measurement by controlled-release vs. resonance methods.

    NARCIS (Netherlands)

    Hof, AL; Boom, H; Robinson, C; Rutten, W; Neuman, M; Wijkstra, H

    1997-01-01

    With a newly developed Controlled-Release Ergometer the complete characteristic of the series elastic component can be measured in human muscles. Previous estimates were based on the resonance method: muscle elasticity was assessed from the resonance frequency of the muscle elasticity connected to a

  13. Age and muscle-dependent variations in corticospinal excitability during standing tasks.

    Directory of Open Access Journals (Sweden)

    Anthony Remaud

    Full Text Available In this study, we investigated how modulation in corticospinal excitability elicited in the context of standing tasks varies as a function of age and between muscles. Changes in motor evoked potentials (MEPs recorded in tibialis anterior (TA and gastrocnemius lateralis (GL were monitored while participants (young, n = 10; seniors, n = 11 either quietly stood (QS or performed a heel raise (HR task. In the later condition, transcranial magnetic stimulation (TMS pulses were delivered at three specific time points during the task: 1 250 ms before the "go" cue (preparatory (PREP phase, 2 100 ms before the heel rise (anticipatory postural adjustment (APA phase, and 3 200 ms after heel rise (execution (EXEC phase. In each task and each phase, variations in MEP characteristics were analysed for age and muscle-dependent effects. Variations in silent period (SP duration were also examined for certain phases (APA and EXEC. Our analysis revealed no major difference during QS, as participants exhibited very similar patterns of modulation in both TA and GL, irrespective of their age group. During the HR task, young adults exhibited a differential modulation in the PREP phase with enhanced responses in TA relative to GL, which was not seen in seniors. Finally, besides differences in MEP latency, age had little influence on MEP modulation during the APA and EXEC phases, where amplitude was largely a function of background muscle activity associated with each phase (i.e., APA: TA; EXEC: GL. No age or muscle effects were detected for SP measurements. Overall, our results revealed no major differences between young adults and healthy seniors in the ability to modulate corticospinal facilitation destined to ankle muscles during standing tasks, with maybe the exception of the ability to prime muscle synergies in the preparatory phase of action.

  14. Age changes in human bone: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, W.D.

    1977-12-03

    The human skeleton steadily changes structure and mass during life because of a variety of internal and external factors. Extracellular substance and bone cells get old, characteristic structural remodeling occurs with age and these age-related changes are important in the discrimination between pathological and physiological changes. Perhaps 20 percent of the bone mass is lost between the fourth and the ninth decades, osteoblasts function less efficiently and gradual loss of bone substance is enhanced by delayed mineralization of an increased surface area of thin and relatively less active osteoid seams. After the fifth decade, osteoclasia and the number of Howship's lacunae increase, and with age, the number of large osteolytic osteocytes increases as the number of small osteocytes declines and empty osteocyte lacunae become more common. The result is greater liability to fracture and diminished healing or replacement of injured bone.

  15. Effects of walking speed and age on the muscle forces of unimpaired gait subjects

    Science.gov (United States)

    Fliger, Carlos G.; Crespo, Marcos J.; Braidot, Ariel A.; Ravera, Emiliano P.

    2016-04-01

    Clinical gait analysis provides great contributions to the understanding of gait disorders and also provides a mean for a more comprehensive treatment plan. However, direct measures of muscle forces are difficult to obtain in clinical settings because it generally requires invasive techniques. Techniques of musculoskeletal modeling have been used for several decades to improve the benefits of clinical gait analysis, but many of the previous studies were focused on analyzing separately the muscle forces distribution of children or adult subjects with only one condition of walking speed. For these reason, the present study aims to enhance the current literature by describing the age and speed gait effects on muscle forces during walking. We used a musculoskeletal model with 23 degrees of freedom and 92 musculotendon actuators to represent 76 muscles in the lower extremities and torso. The computed muscle control algorithm was used to estimate the muscle forces from the kinematics and to adjust the model obtained in the residual reduction algorithm. We find that hamstrings has an important peak in the mid-stance phase in the adult group but this peak disappears in the children group with the same walking speed condition. Furthermore, the rectus femoris presents an increase in the muscle force during the pre- and mid-swing in concordance with the increment in the walking speed of subjects. This behavior could be associated with the role that the rectus femoris has in the acceleration of the knee joint. Finally, we show that the soleus is the muscle that perform the major force throughout the gait cycle regardless of age and walking speed.

  16. Meat quality traits in the emu (Dromaius novaehollandiae) as affected by muscle type and animal age.

    Science.gov (United States)

    Berge, P; Lepetit, J; Renerre, M; Touraille, C

    1997-02-01

    Meat quality traits were determined in the major muscles of the emu (Dromaius novaehollandiae) at different slaughter ages (6, 10, 14, 17 or ≥20 months). A mean ultimate pH value of 5.5 was reached within around 3 h post mortem, but this value was 6.1 in animals that had suffered a preslaughter stress (transportation and fasting). The collagen and pigment contents varied widely among the muscles. The protein and pigment contents increased with animal age, but this effect was perceptible only between 6 and 14 months. The other chemical constituents were little affected by muscle type or animal age. The intense red colour of emu meat, due to a high pigment content, was very sensitive to oxidation, thus limiting the storage of fresh meat under aerobic conditions to short periods of time. Despite a rapid post-mortem tenderization (≤24 h), the residual myofibrillar strength obtained after extended ageing remained intermediate between those reported for chicken and beef. The tenderness of meat, cooked to 60 °C, differed between muscles and decreased with increasing age, thus reflecting the changes occuring in the concentration and in the heat stability of the intramuscular connective tissue.

  17. The influence of training status, age, and muscle fiber type on cycling efficiency and endurance performance.

    Science.gov (United States)

    Hopker, James G; Coleman, Damian A; Gregson, Hannah C; Jobson, Simon A; Von der Haar, Tobias; Wiles, Jonathan; Passfield, Louis

    2013-09-01

    The purpose of this study was to assess the influence of age, training status, and muscle fiber-type distribution on cycling efficiency. Forty men were recruited into one of four groups: young and old trained cyclists, and young and old untrained individuals. All participants completed an incremental ramp test to measure their peak O2 uptake, maximal heart rate, and maximal minute power output; a submaximal test of cycling gross efficiency (GE) at a series of absolute and relative work rates; and, in trained participants only, a 1-h cycling time trial. Finally, all participants underwent a muscle biopsy of their right vastus lateralis muscle. At relative work rates, a general linear model found significant main effects of age and training status on GE (P 0.05). Power output in the 1-h performance trial was predicted by average O2 uptake and GE, with standardized β-coefficients of 0.94 and 0.34, respectively, although some mathematical coupling is evident. These data demonstrate that muscle fiber type does not affect cycling efficiency and was not influenced by the aging process. Cycling efficiency and the percentage of type I muscle fibers were influenced by training status, but only GE at 120 revolutions/min was seen to predict cycling performance.

  18. The Age of Human Cerebral Cortex Neurons

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, R D; Curtis, M A; Spalding, K L; Buchholz, B A; Fink, D; Bjork-Eriksson, T; Nordborg, C; Gage, F H; Druid, H; Eriksson, P S; Frisen, J

    2006-04-06

    The traditional static view of the adult mammalian brain has been challenged by the realization of continuous generation of neurons from stem cells. Based mainly on studies in experimental animals, adult neurogenesis may contribute to recovery after brain insults and decreased neurogenesis has been implicated in the pathogenesis of neurological and psychiatric diseases in man. The extent of neurogenesis in the adult human brain has, however, been difficult to establish. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral cortex. Together with the analysis of the cortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that whereas non-neuronal cells turn over, neurons in the human cerebral cortex are not generated postnatally at detectable levels, but are as old as the individual.

  19. Expression profiles of muscle disease-associated genes and their isoforms during differentiation of cultured human skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Abdul-Hussein Saba

    2012-12-01

    Full Text Available Abstract Background The formation of contractile myofibrils requires the stepwise onset of expression of muscle specific proteins. It is likely that elucidation of the expression patterns of muscle-specific sarcomeric proteins is important to understand muscle disorders originating from defects in contractile sarcomeric proteins. Methods We investigated the expression profile of a panel of sarcomeric components with a focus on proteins associated with a group of congenital disorders. The analyses were performed in cultured human skeletal muscle cells during myoblast proliferation and myotube development. Results Our culture technique resulted in the development of striated myotubes and the expression of adult isoforms of the sarcomeric proteins, such as fast TnI, fast TnT, adult fast and slow MyHC isoforms and predominantly skeletal muscle rather than cardiac actin. Many proteins involved in muscle diseases, such as beta tropomyosin, slow TnI, slow MyBPC and cardiac TnI were readily detected in the initial stages of muscle cell differentiation, suggesting the possibility of an early role for these proteins as constituent of the developing contractile apparatus during myofibrillogenesis. This suggests that in disease conditions the mechanisms of pathogenesis for each of the mutated sarcomeric proteins might be reflected by altered expression patterns, and disturbed assembly of cytoskeletal, myofibrillar structures and muscle development. Conclusions In conclusion, we here confirm that cell cultures of human skeletal muscle are an appropriate tool to study developmental stages of myofibrillogenesis. The expression of several disease-associated proteins indicates that they might be a useful model system for studying the pathogenesis of muscle diseases caused by defects in specific sarcomeric constituents.

  20. Immune response and mitochondrial metabolism are commonly deregulated in DMD and aging skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Daniel Baron

    Full Text Available Duchenne Muscular Dystrophy (DMD is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed, of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1 or the mitochondrial metabolism (ESRRA. Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors.

  1. Immune response and mitochondrial metabolism are commonly deregulated in DMD and aging skeletal muscle.

    Science.gov (United States)

    Baron, Daniel; Magot, Armelle; Ramstein, Gérard; Steenman, Marja; Fayet, Guillemette; Chevalier, Catherine; Jourdon, Philippe; Houlgatte, Rémi; Savagner, Frédérique; Pereon, Yann

    2011-01-01

    Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors.

  2. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    DEFF Research Database (Denmark)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees......, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy...... metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized...

  3. Load and failure behavior of human muscle samples in the context of proximal femur replacement

    OpenAIRE

    Schleifenbaum, Stefan; Schmidt, Michael; Möbius, Robert; Wolfskämpf, Thomas; Schröder, Christian; Grunert, Ronny; Hammer, Niels; Prietzel, Torsten

    2016-01-01

    Background: To ensure adequate function after orthopedic tumor reconstruction, it is important to reattach the remaining soft tissue to the implant. This study aimed at obtaining mechanical properties of textile muscle-implant and muscle-bone connections in a preliminary test. Methods: Two groups of soft-tissue attachment were mechanically tested and compared: Native bone-muscle samples obtained from human femora and muscles attached to a prosthetic implant by means of Trevira® attachment tu...

  4. Effect of Preexercise Creatine Ingestion on Muscle Performance in Healthy Aging Males.

    Science.gov (United States)

    Baker, Taylor P; Candow, Darren G; Farthing, Jonathan P

    2016-06-01

    Preexercise creatine supplementation may have a beneficial effect on aging muscle performance. Using a double-blind, repeated measures, crossover design, healthy males (N = 9, 54.8 ± 4.3 years; 92.9 ± 11.5 kg; 179.2 ± 11.1 cm) were randomized to consume creatine (20 g) and placebo (20 g corn starch maltodextrin), on 2 separate occasions (7 days apart), 3 hours before performing leg press and chest press repetitions to muscle fatigue (3 sets at 70% 1-repetition maximum; 1 minute rest between sets). There was a set main effect (p ≤ 0.05) for the leg press and chest press with the number of repetitions performed decreasing similarly for creatine and placebo. These results suggest that a bolus ingestion of creatine consumed 3 hours before resistance exercise has no effect on upper or lower-body muscle performance in healthy aging males.

  5. Muscle Patterning in Mouse and Human Abdominal Wall Development and Omphalocele Specimens of Humans

    OpenAIRE

    Nichol, Peter F.; Corliss, Robert F.; Yamada, Shigehito; SHIOTA, KOHEI; Saijoh, Yukio

    2012-01-01

    Human omphalocele is a congenital defect of the abdominal wall in which the secondary abdominal wall structures (muscle and connective tissue) in an area centered around the umbilicus are replaced by a translucent membranous layer of tissue. Histological examination of omphalocele development and moreover the staging of normal human abdominal wall development has never been described. We hypothesized that omphalocele is the result of an arrest in the secondary abdominal wall development and p...

  6. Fiber-type composition of the human jaw muscles--(part 2) role of hybrid fibers and factors responsible for inter-individual variation.

    Science.gov (United States)

    Korfage, J A M; Koolstra, J H; Langenbach, G E J; van Eijden, T M G J

    2005-09-01

    This is the second of two articles about fiber-type composition of the human jaw muscles. It reviews the functional relationship of hybrid fibers and the adaptive properties of jaw-muscle fibers. In addition, to explain inter-individual variation in fiber-type composition, we discuss these adaptive properties in relation to environmental stimuli or perturbations. The fiber-type composition of the human jaw muscles is very different from that of limb and trunk muscles. Apart from the presence of the usual type I, IIA, and IIX myosin heavy-chains (MyHC), human jaw-muscle fibers contain MyHCs that are typical for developing or cardiac muscle. In addition, much more frequently than in limb and trunk muscles, jaw-muscle fibers are hybrid, i.e., they contain more than one type of MyHC isoform. Since these fibers have contractile properties that differ from those of pure fibers, this relatively large quantity of hybrid fibers provides a mechanism that produces a very fine gradation of force and movement. The presence of hybrid fibers might also reflect the adaptive capacity of jaw-muscle fibers. The capacity for adaptation also explains the observed large inter-individual variability in fiber-type composition. Besides local influences, like the amount of muscle activation and/or stretch, more general influences, like aging and gender, also play a role in the composition of fiber types.

  7. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration.

    Science.gov (United States)

    Choi, Ji Suk; Yoon, Hwa In; Lee, Kyoung Soo; Choi, Young Chan; Yang, Seong Hyun; Kim, In-San; Cho, Yong Woo

    2016-01-28

    Exosomes released from skeletal muscle cells play important roles in myogenesis and muscle development via the transfer of specific signal molecules. In this study, we investigated whether exosomes secreted during myotube differentiation from human skeletal myoblasts (HSkM) could induce a cellular response from human adipose-derived stem cells (HASCs) and enhance muscle regeneration in a muscle laceration mouse model. The exosomes contained various signal molecules including myogenic growth factors related to muscle development, such as insulin-like growth factors (IGFs), hepatocyte growth factor (HGF), fibroblast growth factor-2 (FGF2), and platelet-derived growth factor-AA (PDGF-AA). Interestingly, exosome-treated HASCs fused with neighboring cells at early time points and exhibited a myotube-like phenotype with increased expression of myogenic proteins (myosin heavy chain and desmin). On day 21, mRNAs of terminal myogenic genes were also up-regulated in exosome-treated HASCs. Moreover, in vivo studies demonstrated that exosomes from differentiating HSkM reduced the fibrotic area and increased the number of regenerated myofibers in the injury site, resulting in significant improvement of skeletal muscle regeneration. Our findings suggest that exosomes act as a biochemical cue directing stem cell differentiation and provide a cell-free therapeutic approach for muscle regeneration.

  8. Functional compartmentalization of the human superficial masseter muscle.

    Directory of Open Access Journals (Sweden)

    Rodrigo A Guzmán-Venegas

    Full Text Available Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM muscle's motor units using high-density surface electromyography (EMGs at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF were randomly requested. Using a two-dimensional grid (four columns, six electrodes located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001.The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001. The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001. The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20-60% MVBF.

  9. Functional compartmentalization of the human superficial masseter muscle.

    Science.gov (United States)

    Guzmán-Venegas, Rodrigo A; Biotti Picand, Jorge L; de la Rosa, Francisco J Berral

    2015-01-01

    Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM) muscle's motor units using high-density surface electromyography (EMGs) at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm) were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF) were randomly requested. Using a two-dimensional grid (four columns, six electrodes) located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001).The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001). The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001). The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20-60% MVBF).

  10. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( muscle-wasting disorders.

  11. Nuclear fusion-independent smooth muscle differentiation of human adipose-derived stem cells induced by a smooth muscle environment.

    Science.gov (United States)

    Zhang, Rong; Jack, Gregory S; Rao, Nagesh; Zuk, Patricia; Ignarro, Louis J; Wu, Benjamin; Rodríguez, Larissa V

    2012-03-01

    Human adipose-derived stem cells hASC have been isolated and were shown to have multilineage differentiation capacity. Although both plasticity and cell fusion have been suggested as mechanisms for cell differentiation in vivo, the effect of the local in vivo environment on the differentiation of adipose-derived stem cells has not been evaluated. We previously reported the in vitro capacity of smooth muscle differentiation of these cells. In this study, we evaluate the effect of an in vivo smooth muscle environment in the differentiation of hASC. We studied this by two experimental designs: (a) in vivo evaluation of smooth muscle differentiation of hASC injected into a smooth muscle environment and (b) in vitro evaluation of smooth muscle differentiation capacity of hASC exposed to bladder smooth muscle cells. Our results indicate a time-dependent differentiation of hASC into mature smooth muscle cells when these cells are injected into the smooth musculature of the urinary bladder. Similar findings were seen when the cells were cocultured in vitro with primary bladder smooth muscle cells. Chromosomal analysis demonstrated that microenvironment cues rather than nuclear fusion are responsible for this differentiation. We conclude that cell plasticity is present in hASCs, and their differentiation is accomplished in the absence of nuclear fusion.

  12. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( muscle-wasting disorders.

  13. Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium.

    Science.gov (United States)

    Nam, Mi-Hyun; Son, Won-Rak; Lee, Young Sik; Lee, Kwang-Won

    Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-α and interleukin-1β via extracellular-signal-regulated kinases phosphorylation and nuclear factor-κB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.

  14. Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

    Science.gov (United States)

    Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

    2015-02-01

    Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.

  15. Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice

    DEFF Research Database (Denmark)

    Ringholm, Stine; Olesen, Jesper; Pedersen, Jesper Thorhauge;

    2013-01-01

    The present study tested the hypothesis that lifelong resveratrol (RSV) supplementation counteracts an age-associated decrease in skeletal muscle oxidative capacity through peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and that RSV combined with lifelong exercise training (ET...

  16. Aging impairs the recovery in mechanical muscle function following 4 days of disuse

    DEFF Research Database (Denmark)

    Hvid, L G; Suetta, C; Nielsen, J H

    2014-01-01

    As aged individuals are frequently exposed to short-term disuse caused by disease or musculoskeletal injury, it is important to understand how short-term disuse and subsequent retraining affect lower limb mechanical muscle function. The purpose of the present study was, therefore, to investigate ...

  17. DEVELOPMENT OF MUSCLE POWER IN PRETERM INFANTS - INDIVIDUAL TRAJECTORIES AFTER TERM AGE

    NARCIS (Netherlands)

    DEGROOT, L; HOPKINS, B; TOUWEN, BCL; VANDERHOEK, AM

    1993-01-01

    In a longitudinal study individual trajectories were traced for the developing relationship between active and passive muscle power in preterm (n = 37) and fullterm (n = 20) infants from term to 24 weeks (corrected) age. Such trajectories should enable the identification of those infants at highest

  18. Protein intake and exercise for optimal muscle function with aging: Recommendations from the ESPEN Expert Group

    Science.gov (United States)

    Deutz, Nicolaas E. P.; Bauer, Jurgen M.; Barazzoni, Rocco; Biolo, Gianni; Boirie, Yves; Bosy-Westphal, Anja; Cederholm, Tommy; Cruz-Jentoft, Alfonso; Krznaric, Zeljko; Nair, K. Sreekumaran; Singer, Pierre; Teta, Daniel; Tipton, Kevin; Calder, Philip C.

    2014-01-01

    The aging process is associated with gradual and progressive loss of muscle mass along with lowered strength and physical endurance. This condition, sarcopenia, has been widely observed with aging in sedentary adults. Regular aerobic and resistance exercise programs have been shown to counteract most aspects of sarcopenia. In addition, good nutrition, especially adequate protein and energy intake, can help limit and treat age-related declines in muscle mass, strength, and functional abilities. Protein nutrition in combination with exercise is considered optimal for maintaining muscle function. With the goal of providing recommendations for health care professionals to help older adults sustain muscle strength and function into older age, the European Society for Clinical Nutrition and Metabolism (ESPEN) hosted a Workshop on Protein Requirements in the Elderly, held in Dubrovnik on November 24 and 25, 2013. Based on the evidence presented and discussed, the following recommendations are made: (1) for healthy older people, the diet should provide at least 1.0 to 1.2 g protein/kg body weight/day (2) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2 to 1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury, and (3) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible. PMID:24814383

  19. Bitter taste receptor polymorphisms and human aging.

    Directory of Open Access Journals (Sweden)

    Daniele Campa

    Full Text Available Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001 with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics.

  20. Chronological ageing of human hair keratin fibres.

    Science.gov (United States)

    Thibaut, S; de Becker, E; Bernard, B A; Huart, M; Fiat, F; Baghdadli, N; Luengo, G S; Leroy, F; Angevin, P; Kermoal, A M; Muller, S; Peron, M; Provot, G; Kravtchenko, S; Saint-Léger, D; Desbois, G; Gauchet, L; Nowbuth, K; Galliano, A; Kempf, J Y; Silberzan, I

    2010-12-01

    Examination of very long hair (length > 2.4 m) using a large range of evaluation methods including physical, chemical, biochemical and microscopic techniques has enabled to attain a detailed understanding of natural ageing of human hair keratin fibres. Scrutinizing hair that has undergone little or no oxidative aggression--because of the absence of action of chemical agents such as bleaching or dyeing--from the root to the tip shows the deterioration process, which gradually takes place from the outside to the inside of the hair shaft: first, a progressive abrasion of the cuticle, whilst the cortex structure remains unaltered, is evidenced along a length of roughly 1 m onwards together with constant shine, hydrophobicity and friction characteristics. Further along the fibre, a significant damage to cuticle scales occurs, which correlates well with ceramides and 18-Methyl Eicosanoic Acid (18-MEA) decline, and progressive decrease in keratin-associated protein content. Most physical descriptors of mechanical and optical properties decay significantly. This detailed description of natural ageing of human hair fibres by a fine analysis of hair components and physical parameters in relationship with cosmetic characteristics provides a time-dependent 'damage scale' of human hair, which may help in designing new targeted hair care formulations.

  1. The molecular responses of skeletal muscle satellite cells to continuous expression of IGF-1: implications for the rescue of induced muscular atrophy in aged rats

    Science.gov (United States)

    Chakravarthy, M. V.; Booth, F. W.; Spangenburg, E. E.

    2001-01-01

    Approximately 50% of humans older than 85 years have physical frailty due to weak skeletal muscles. This indicates a need for determining mechanisms to combat this problem. A critical cellular factor for postnatal muscle growth is a population of myogenic precursor cells called satellite cells. Given the complex process of sarcopenia, it has been postulated that, at some point in this process, a limited satellite cell proliferation potential could become rate-limiting to the regrowth of old muscles. It is conceivable that if satellite cell proliferative capacity can be maintained or enhanced with advanced age, sarcopenia could potentially be delayed or prevented. Therefore, the purposes of this paper are to describe whether IGF-I can prevent muscular atrophy induced by repeated cycles of hindlimb immobilization, increase the in vitro proliferation in satellite cells from these muscles and, if so, the molecular mechanisms by which IGF-I mediates this increased proliferation. Our results provide evidence that IGF-I can enhance aged muscle regrowth possibly through increased satellite cell proliferation. The results also suggest that IGF-I enhances satellite cell proliferation by decreasing the cell cycle inhibitor, p27Kip1, through the PI3'-K/Akt pathway. These data provide molecular evidence for IGF-I's rescue effect upon aging-associated skeletal muscle atrophy.

  2. Effects of muscle type, castration, age, and compensatory growth rate on androgen receptor mRNA expression in bovine skeletal muscle.

    Science.gov (United States)

    Brandstetter, A M; Pfaffl, M W; Hocquette, J F; Gerrard, D E; Picard, B; Geay, Y; Sauerwein, H

    2000-03-01

    The effect of testosterone on sexual dimorphism is evident by differential growth of forelimb and neck muscles in bulls and steers. Divergent hormone sensitivites may account for the differential growth rates of individual muscles. Therefore, the objective of this study was to compare androgen receptor (AR) expression in three different muscles of bulls and steers at various ages and growth rates. Thirty Montbéliard bulls and 30 steers were assigned to four slaughter age groups. Four or five animals of each sex were slaughtered at 4 and 8 mo of age. Animals in the remaining two slaughter groups (12 and 16 mo) were divided into groups of either restricted (R) or ad libitum (AL) access to feed. Five animals of each sex and diet were slaughtered at the end of the restricted intake period at 12 mo of age. To simulate compensatory growth, the remaining animals (R and AL) were allowed ad libitum access to feed until slaughter at 16 mo of age. Total RNA was extracted from samples of semitendinosus (ST), triceps brachii (TB), and splenius (SP) muscles. Androgen receptor mRNA was quantified in 200-ng total RNA preparations using an internally standardized reverse transcription (RT) PCR assay. Data were analyzed using 18S ribosomal RNA concentrations as a covariable. Steers had higher AR mRNA levels per RNA unit than bulls (P muscles (P muscle with increasing age. Between 4 and 12 mo of age, AR mRNA levels increased (P muscle AR expression, but steers exhibiting compensatory growth had higher AR mRNA levels than AL steers (P muscle-specific and may be modulated by circulating testicular hormones. These data suggest that the regulation of AR expression may be linked to allometric muscle growth patterns in cattle and compensatory gain in steers.

  3. The application of blood flow measurements to the study of aging muscle.

    Science.gov (United States)

    McCully, K K; Posner, J D

    1995-11-01

    Blood flow to skeletal muscle is a potentially important factor in the reduction of muscle function associated with aging (sarcopenia). The main influence of reduced blood flow capacity on muscle function is in limiting oxidative metabolism. Direct measures of blood flow include: intravital-microscopy, plethysmography, radioactive microspheres, 133Xenon washout, thermodilution, and Doppler ultrasound. Indirect measurement of blood flow includes arm-to-ankle pressure index and the rate of phosphocreatine recovery after exercise. Several new methodologies have been developed to evaluate muscle blood flow, including color-Doppler imaging, magnetic resonance imaging/angiography (MRI/MRA), and near-infrared spectroscopy (NIRS). As adaptations of traditional techniques, these methods promise more precise information under less invasive conditions. MRI is an expensive and technically challenging method able to measure vessel location, blood flow, and wall diameter in blood vessels throughout the cardiac cycle. Color-Doppler provides excellent temporal resolution blood flow throughout the cardiac cycle, along with some anatomical information. NIRS is an inexpensive and portable technology that can measure changes in oxygen saturation and provide information on tissue oxygen delivery in studies of frailer and more difficult-to-study subjects. Muscle blood flow is not thought to limit oxidative metabolism under normal conditions in young individuals. However, it is not clear what happens to muscle blood flow in healthy older individuals. Reduced capillary density, less maximal blood flow, and a slower hyperemic flow response have been reported in some, but not all, studies. Further studies with the newer methodologies are needed to re-examine age-related changes in muscle blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Acute effects of stretching exercise on the soleus muscle of female aged rats.

    Science.gov (United States)

    Zotz, Talita Gnoato; Capriglione, Luiz Guilherme A; Zotz, Rafael; Noronha, Lucia; Viola De Azevedo, Marina Louise; Fiuza Martins, Hilana Rickli; Silveira Gomes, Anna Raquel

    2016-01-01

    It has been shown that stretching exercises can improve the flexibility and independence of the elderly. However, although these exercises commonly constitute training programs, the morphological adaptations induced by stretching exercises in aged skeletal muscle are still unclear. To assess the acute effects of passive mechanical static stretching on the morphology, sarcomerogenesis and modulation of important components of the extracellular matrix of the soleus muscle of aged female rats. Fifteen old female rats with 26 months were divided into two groups: stretching (n=8, SG) and control (n=7, CG): The stretching protocol consisted of 4 repetitions each of 1 min with 30s interval between sets. Stretching was performed on the left soleus muscle, 3 times a week for 1 week. After three sessions, the rats were anesthetized to remove the left soleus muscle, and then euthanized. The following analyses were carried out: muscle fiber cross-sectional area and serial sarcomere number; immunohistochemistry for the quantification of collagen I, III and TGFβ-1. a decrease in muscle fiber cross-sectional area of the SG was observed when compared to the CG (p=0.0001, Kruskal-Wallis); the percentage of type I collagen was significantly lower in the SG when compared to the CG (p=0.01, Kruskal-Wallis), as well as the percentage of TGFβ-1 (p=0.04, Kruskal-Wallis); collagen III was significantly higher in the SG than in the CG (7.06±6.88% vs 4.92±5.30%, p=0.01, Kruskal-Wallis). Although the acute stretching induced muscle hypotrophy, an antifibrotic action was detected. Copyright © 2015 Elsevier GmbH. All rights reserved.

  5. Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

    Science.gov (United States)

    Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

    2017-01-01

    This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature (P < 0.05). This result indicated that repeated local muscle cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

  6. Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

    Science.gov (United States)

    Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

    2017-07-01

    This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature ( P muscle cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

  7. Characterization of human carbonic anhydrase III from skeletal muscle.

    Science.gov (United States)

    Carter, N; Jeffery, S; Shiels, A; Edwards, Y; Tipler, T; Hopkinson, D A

    1979-10-01

    A third form of human carbonic anhydrase (CA III), found at high concentrations in skeletal muscle, has been purified and characterized. This isozyme shows relatively poor hydratase and esterase activities compared to the red cell isozymes, CA I and CA II, but is similar to these isozymes in subunit structure (monomer) and molecular size (28,000). CA III is liable to posttranslational modification by thiol group interaction. Monomeric secondary isozymes, sensitive to beta-mercaptoethanol, are found in both crude and purified material and can be generated in vitro by the addition of thiol reagents. Active dimeric isozymes, generated apparently by the formation of intermolecular disulfide bridges, also occur but account for only a small proportion of the total protein and appear only when the concentration of CA III is particularly high.

  8. Regional neuromuscular regulation within human rectus femoris muscle during gait.

    Science.gov (United States)

    Watanabe, Kohei; Kouzaki, Motoki; Moritani, Toshio

    2014-11-01

    The spatial distribution pattern of neuromuscular activation within the human rectus femoris (RF) muscle was investigated during gait by multi-channel surface electromyography (surface EMG). Eleven healthy men walked on a treadmill with three gait speeds (4, 5, and 6 km/h) and gradients (0°, 12.5°, and 25°). The spatial distribution of surface EMG was tested by central locus activation (CLA), which is calculated from 2-D multi-channel surface EMG with 46 surface electrodes. For all conditions, CLA was around the middle regions during the swing-to-stance transition and moved in a proximal direction during the stance phase and stance-to-swing transition (pphase significantly moved to proximal site with increasing gait speed (pphases, with increasing grade, CLA significantly moved distally (pgait cycle and is non-uniformly regulated longitudinally.

  9. Human eosinophil–airway smooth muscle cell interactions

    Directory of Open Access Journals (Sweden)

    J. Margaret Hughes

    2000-01-01

    Full Text Available Eosinophils are present throughout the airway wall of asthmatics. The nature of the interaction between human airway smooth muscle cells (ASMC and eosinophils was investigated in this study. We demonstrated, using light microscopy, that freshly isolated eosinophils from healthy donors rapidly attach to ASMC in vitro. Numbers of attached eosinophils were highest at 2 h, falling to 50% of maximum by 20 h. Eosinophil attachment at 2 h was reduced to 72% of control by anti-VCAM-1, and to 74% at 20 h by anti-ICAM-1. Pre-treatment of ASMC for 24 h with TNF-α, 10 nM, significantly increased eosinophil adhesion to 149 and 157% of control after 2 and 20 h. These results provide evidence that eosinophil interactions with ASMC involve VCAM-1 and ICAM-1 and are modulated by TNF-α.

  10. Presbyopia - a maverick of human aging.

    Science.gov (United States)

    Pierścionek, B K; Weale, R A

    1995-01-01

    The aim of this study was to examine the extent to which the age-related variations of properties of the human lens may be able to account for presbyopia. Dimensionless linear regressions were calculated for age-related biological functions with special reference to ocular and lenticular ones. Their intercepts on the x-(age-)axis are compared, and their distribution is analyzed. An analysis was made of the effect of the growth of the lens on the relation between its shape and the proximal zonular anchorages on the one hand and the age-related variation of the angle between the zonule and the equatorial plane of the lens. The lens is not unusual in seeming to have evolved in support of a life-span of about 120 years. Presbyopia, however, fails to fit into the general picture and this is hypothesized to result from lenticular growth and a combination of factors which are not all governed by senescence. The potential involvement of the root of the iris throws an interesting light on the apparently worldwide variation of the condition.

  11. Age-related differences of neutrophil activation in a skeletal muscle ischemia-reperfusion model.

    Science.gov (United States)

    Mowlavi, Arian; Reynolds, Christopher; Neumeister, Michael W; Wilhelmi, Bradon J; Song, Yao-Hua; Naffziger, Ryan; Glatz, Frank R; Russell, Robert C

    2003-04-01

    Free tissue transfers and replantation of amputated limbs are better tolerated by young adolescents than mature adults. The authors hypothesized that this observation may be, in part, because of an attenuated ischemia-reperfusion (IR) injury in younger patients. Because neutrophils have been identified as a critical cell line responsible for IR injury, the authors investigated the effects of animal age on the degree of neutrophil activation in a rat model. Activation was evaluated by monitoring expression of integrin surface markers (mean fluorescence intensity [MFI] of CD11b) and oxidative burst potential (MFI of dihydrorhodamine [DHR] oxidation) by flow cytometry in neutrophils analyzed after 4 hours of ischemia and 1, 4, and 16 hours of reperfusion in a gracilis muscle flap model in mature adult and young adolescent rats. Neutrophil activation was also evaluated in control sham-operated animals, which underwent elevation of gracilis muscle flaps without exposure to an ischemic insult. Muscle edema, determined by wet-to-dry muscle weight ratio, and muscle viability, determined by nitro blue tetrazolium (NBT) staining, were completed for gracilis muscles exposed to ischemia after 24 hours of reperfusion for each of the groups. Integrin expression, assessed by MFI of CD11b, was increased significantly in ischemic muscles of mature adult rats at 4 hours of reperfusion (71.10+/-3.53 MFI vs. 54.88+/-12.73 MFI, p=0.025). Neutrophil oxidative potential, assessed by MFI of DHR oxidation, was increased significantly in ischemic muscles of mature adult rats compared with young adolescent rats at 1 hour of reperfusion (78.10+/-9.53 MFI vs. 51.78+/-16.91 MFI, p=0.035) and 4 hours of reperfusion (83.69+/-15.29 MFI vs. 46.55+/-8.09 MFI, p=0.005). Increased edema formation was observed in the ischemic muscles of mature adult rats when compared with young adolescent rats (1.25+/-0.04 vs. 1.12+/-0.05, p=0.031) after 24 hours of reperfusion. A trend toward decreased muscle

  12. Noninvasive skeletal muscle lactate detection between periods of intense exercise in humans.

    Science.gov (United States)

    Mercier, B; Granier, P; Mercier, J; Foucat, L; Bielicki, G; Pradere, J; Renou, J P; Prefaut, C

    1998-06-01

    We investigated whether localized 1H nuclear magnetic resonance spectroscopy (NMRS) using stimulated echoes (STEAM) with a long mixing time (t(m)) allowed the suppression of the fat signal and detection of lactate in skeletal muscle. The 1H NMRS sequence was first validated in three isolated and perfused rabbit biceps brachii muscles. Spectra were obtained on a wide-bore spectrometer using a dual-tuned probe (1H and 31P). Death was simulated by ceasing the muscle perfusion, which allowed post-mortem changes to be followed. During and after the simulated death, changes in levels of pH and in content of energy-rich compounds were observed with 31P NMRS. Our results showed an inverse linear relationship between pH and lactate in each of the three rabbits (r = 0.93, P recovery between periods of intense exercise (force-velocity test, F-v test). Seven subjects mean age 25.1 (SEM 0.8) years participated in this study. Soleus muscle lactate was detected at rest and for 3 min 30 s of the 5-min recovery between periods using a 2.35-T 40-cm bore magnet spectrometer. Arm venous plasma lactate concentration was measured at rest, during the F-v test when the subject stopped pedalling (S1), and at the end of each 5-min recovery between periods (S2). Results showed that the venous plasma lactate concentration at S1 and S2 increased significantly from the beginning of the F-v test to peak anaerobic power (W(an,peak)) (P braking forces (P < 0.05). We concluded from these results that localized 1H NMRS using STEAM with a long t(m) allows suppression of the fat signal and repeated detection of lactate on isolated perfused skeletal muscle in animals and between periods of intense exercise in humans.

  13. Influence of knee flexion angle and age on triceps surae muscle activity during heel raises.

    Science.gov (United States)

    Hébert-Losier, Kim; Schneiders, Anthony G; García, José A; Sullivan, S John; Simoneau, Guy G

    2012-11-01

    Triceps surae and Achilles tendon injuries are frequent in sports medicine, particularly in middle-aged adults. Muscle imbalances and weakness are suggested to be involved in the etiology of these conditions, with heel-raise testing often used to assess and treat triceps surae (TS) injuries. Although heel raises are recommended with the knee straight for gastrocnemius and bent for soleus (SOL), the extent of muscle selectivity in these positions is not clear. This study aimed to determine the influence of knee angle and age on TS muscle activity during heel raises. Forty-eight healthy men and women were recruited from a younger-aged (18-25 years) and middle-aged (35-45 years) population. All the subjects performed unilateral heel raises in 0° and 45° knee flexion (KF). Soleus, gastrocnemius medialis (GM) and gastrocnemius lateralis (GL) surface electromyography signals were processed to compute root-mean-square amplitudes, and data were analyzed using mixed-effects models and stepwise regression. The mean TS activity during heel raises was 23% of maximum voluntary isometric contraction when performed in 0° KF and 21% when in 45°. Amplitudes were significantly different between TS muscles (p < 0.001) and KF angles (p < 0.001), with a significant interaction (p < 0.001). However, the age of the population did not influence the results (p = 0.193). The findings demonstrate that SOL activity was 4% greater when tested in 45° compared with 0° KF and 5% lower in the GM and GL. The results are consistent with the recommended use of heel raises in select knee positions for assessing, training, and rehabilitating the SOL and gastrocnemius muscles; however, the 4-5% documented change in activity might not be enough to significantly influence clinical outcome measures or muscle-specific benefits. Contrary to expectations, TS activity did not distinguish between middle-aged and younger-aged adults, despite the higher injury prevalence in middle age.

  14. Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration.

    Science.gov (United States)

    de la Garza-Rodea, Anabel S; Boersma, Hester; Dambrot, Cheryl; de Vries, Antoine Af; van Bekkum, Dirk W; Knaän-Shanzer, Shoshan

    2015-05-20

    To study regeneration of damaged human and murine muscle implants and the contribution of added xenogeneic mesenchymal stem cells (MSCs). Minced human or mouse skeletal muscle tissues were implanted together with human or mouse MSCs subcutaneously on the back of non-obese diabetic/severe combined immunodeficient mice. The muscle tissues (both human and murine) were minced with scalpels into small pieces (< 1 mm(3)) and aliquoted in portions of 200 mm(3). These portions were either cryopreserved in 10% dimethylsulfoxide or freshly implanted. Syngeneic or xenogeneic MSCs were added to the minced muscles directly before implantation. Implants were collected at 7, 14, 30 or 45 d after transplantation and processed for (immuno)histological analysis. The progression of muscle regeneration was assessed using a standard histological staining (hematoxylin-phloxin-saffron). Antibodies recognizing Pax7 and von Willebrand factor were used to detect the presence of satellite cells and blood vessels, respectively. To enable detection of the bone marrow-derived MSCs or their derivatives we used MSCs previously transduced with lentiviral vectors expressing a cytoplasmic LacZ gene. X-gal staining of the fixed tissues was used to detect β-galactosidase-positive cells and myofibers. Myoregeneration in implants of fresh murine muscle was evident as early as day 7, and progressed with time to occupy 50% to 70% of the implants. Regeneration of fresh human muscle was slower. These observations of fresh muscle implants were in contrast to the regeneration of cryopreserved murine muscle that proceeded similarly to that of fresh tissue except for day 45 (P < 0.05). Cryopreserved human muscle showed minimal regeneration, suggesting that the freezing procedure was detrimental to human satellite cells. In fresh and cryopreserved mouse muscle supplemented with LacZ-tagged mouse MSCs, β-galactosidase-positive myofibers were identified early after grafting at the well-vascularized periphery of

  15. Profiling of Age-Related Changes in the Tibialis Anterior Muscle Proteome of the mdx Mouse Model of Dystrophinopathy

    Directory of Open Access Journals (Sweden)

    Steven Carberry

    2012-01-01

    Full Text Available X-linked muscular dystrophy is a highly progressive disease of childhood and characterized by primary genetic abnormalities in the dystrophin gene. Senescent mdx specimens were used for a large-scale survey of potential age-related alterations in the dystrophic phenotype, because the established mdx animal model of dystrophinopathy exhibits progressive deterioration of muscle tissue with age. Since the mdx tibialis anterior muscle is a frequently used model system in muscular dystrophy research, we employed this particular muscle to determine global changes in the dystrophic skeletal muscle proteome. The comparison of mdx mice aged 8 weeks versus 22 months by mass-spectrometry-based proteomics revealed altered expression levels in 8 distinct protein species. Increased levels were shown for carbonic anhydrase, aldolase, and electron transferring flavoprotein, while the expressions of pyruvate kinase, myosin, tropomyosin, and the small heat shock protein Hsp27 were found to be reduced in aged muscle. Immunoblotting confirmed age-dependent changes in the density of key muscle proteins in mdx muscle. Thus, segmental necrosis in mdx tibialis anterior muscle appears to trigger age-related protein perturbations due to dystrophin deficiency. The identification of novel indicators of progressive muscular dystrophy might be useful for the establishment of a muscle subtype-specific biomarker signature of dystrophinopathy.

  16. Interstitial pH in human skeletal muscle during and after dynamic graded exercise

    DEFF Research Database (Denmark)

    Street, D; Bangsbo, Jens; Juel, Carsten

    2001-01-01

    In this study a new method has been used to measure interstitial pH continuously in human muscle during graded exercise. Human subjects performed 5 min of one-legged knee-extensor exercise at power outputs of 30, 50 and 70 W. Muscle interstitial pH was measured continuously in microdialysis...

  17. Growth factor-induced contraction of human bronchial smooth muscle is Rho-kinase-dependent

    NARCIS (Netherlands)

    Gosens, Reinout; Schaafsma, D.; Grootte Bromhaar, M.M; Vrugt, B.; Zaagsma, Hans; Meurs, Herman; Nelemans, Herman

    2004-01-01

    Growth factors have been implicated in the pathophysiology of asthma. However, the putative effects of these growth factors on human airway smooth muscle tone are still largely unknown. We performed contraction experiments using human bronchial smooth muscle ring preparations. The growth factor

  18. A microcalorimetric study of the sodium-potassium-pump and thermogenesis in human skeletal muscle.

    Science.gov (United States)

    Fagher, B; Sjögren, A; Monti, M

    1987-11-01

    Thermogenesis in human skeletal muscle was monitored by measurement of heat production using perfusion microcalorimetry. Heat production significantly correlated with relative body weight. The energy expenditure of the Na-K-pump (delta P), assessed after inhibition by ouabain in Krebs-Ringer phosphate buffer containing glucose and insulin, amounted to 6% of the total heat production in vastus lateralis muscle. Muscle potassium positively correlated with delta P (r = 0.84, P less than 0.005). For rectus abdominis muscle delta P was 8-15%; 95% confidence interval for the difference was 3-5% when comparison was made with vastus lateralis. The finding of a positive relationship between delta P and muscle magnesium (r = 0.68, P less than 0.04) is possibly explained by the dependence of ATP hydrolysis on internal magnesium. Our data on resting thermogenesis in small muscle samples agree to previous estimates of O2 consumption in human skeletal muscle in vivo.

  19. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects

    DEFF Research Database (Denmark)

    Larsen, Steen; Nielsen, Joachim; Neigaard Nielsen, Christina

    2012-01-01

    closely associated these commonly used biochemical measures are to muscle mitochondrial content and muscle oxidative capacity (OXPHOS).Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake (VO(2peak)) and muscle......Skeletal muscle mitochondrial content varies extensively between human subjects. Biochemical measures of mitochondrial proteins, enzyme activities and lipids are often used as markers of mitochondrial content and muscle oxidative capacity (OXPHOS). The purpose of this study was to determine how...... to muscle oxidative capacity followed by complex II activity.We conclude that cardiolipin content, CS and complex I activity are the biomarkers that exhibit the strongest association to mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle....

  20. Age-related differences in twitch properties and muscle activation of the first dorsal interosseous.

    Science.gov (United States)

    Miller, Jonathan D; Herda, Trent J; Trevino, Michael A; Sterczala, Adam J; Ciccone, Anthony B; Nicoll, Justin X

    2017-06-01

    To examine twitch force potentiation and twitch contraction duration, as well as electromyographic amplitude (EMGRMS) and motor unit mean firing rates (MFR) at targeted forces between young and old individuals in the first dorsal interosseous (FDI). Ultrasonography was used to assess muscle quality. Twenty-two young (YG) (age=22.6±2.7years) and 14 older (OD) (age=62.1±4.7years) individuals completed conditioning contractions at 10% and 50% maximal voluntary contraction, (MVC) during which EMGRMS and MFRs were assessed. Evoked twitches preceded and followed the conditioning contractions. Ultrasound images were taken to quantify muscle quality (cross-sectional area [CSA] and echo intensity [EI]). No differences were found between young and old for CSA, pre-conditioning contraction twitch force, or MFRs (P>0.05). However, OD individuals exhibited greater EI and contraction duration (PMFRs. Ultrasonography suggested age-related changes in muscle structure contributed to altered contractile properties in the OD. Greater muscle activation requirements can have negative implications on fatigue resistance at low to moderate intensities in older individuals. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  1. Proteomic identification of age-dependent protein nitration in rat skeletal muscle.

    Science.gov (United States)

    Kanski, Jaroslaw; Alterman, Michail A; Schöneich, Christian

    2003-11-15

    Age-related protein nitration was studied in skeletal muscle of Fisher 344 and Fisher 344/Brown Norway (BN) F1 rats by a proteomic approach. Proteins from young (4 months) and old (24 months) Fisher 344 rats and young (6 months) and old (34 months) Fisher 344/BN F1 animals were separated by 2-D gel electrophoresis. Western blot showed an age-related increase in the nitration of a few specific proteins, which were identified by MALDI-TOF MS and ESI-MS/MS. We identified age-dependent apparent nitration of beta-enolase, alpha-fructose aldolase, and creatine kinase, which perform important functions in muscle energy metabolism, suggesting that the nitration of such key proteins can be, in part, responsible for the decline of muscle motor function of the muscle. Furthermore, we have identified the apparent nitration of succinate dehydrogenase, rab GDP dissociation inhibitor beta (GdI-2), triosephosphate isomerase, troponin I, alpha-crystallin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

  2. Subcellular localization and mechanism of secretion of vascular endothelial growth factor in human skeletal muscle

    DEFF Research Database (Denmark)

    Høier, Birgitte; Prats Gavalda, Clara; Qvortrup, Klaus

    2013-01-01

    The subcellular distribution and secretion of vascular endothelial growth factor (VEGF) was examined in skeletal muscle of healthy humans. Skeletal muscle biopsies were obtained from m.v. lateralis before and after a 2 h bout of cycling exercise. VEGF localization was conducted on preparations...... of teased muscle fibers by transmission electron microscopy (TEM) and confocal microscopy (CM). Muscle interstitial fluid was sampled from microdialysis probes placed in the thigh muscle. TEM and CM analysis revealed two primary sites of localization of VEGF: in vesicles located in the subsarcolemmal...... regions and between the contractile elements within the muscle fibers; and in pericytes situated on the skeletal muscle capillaries. Quantitation of the subsarcolemmal density of VEGF vesicles, calculated on top of myonuclei, in the muscle fibers revealed a ∼50% increase (P...

  3. Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Ling Yang

    2016-01-01

    Full Text Available Calorie restriction (CR retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3–15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001. HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles.

  4. Testosterone therapy preserves muscle strength and power in aging men with type 2 diabete

    DEFF Research Database (Denmark)

    Magnussen, L V; Hvid, L G; Hermann, A P

    2017-01-01

    The purpose of the study was to evaluate whether testosterone replacement therapy improves muscle mechanical and physical function in addition to increasing lean leg mass and total lean body mass in aging men with type 2 diabetes and lowered bio-available testosterone (BioT) levels. Thirty-nine men...... aged 50-70 years with type 2 diabetes and BioT levels center. Patients were randomized to testosterone gel (testosterone replacement therapy, n = 20) or placebo (n = 19) for 24 weeks, applying a double-blinded design. Muscle mechanical...... replacement therapy for 24 weeks compared with placebo, whereas physical function (gait speed) was unchanged in aging men with type 2 diabetes and lowered BioT levels....

  5. Metabolic control of muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher

    2003-01-01

    During muscle contraction, several mechanisms regulate blood flow to ensure a close coupling between muscle oxygen delivery and metabolic demand. No single factor has been identified to constitute the primary metabolic regulator, yet there are signal transduction pathways between skeletal muscle...

  6. A predictive model of muscle excitations based on muscle modularity for a large repertoire of human locomotion conditions

    Directory of Open Access Journals (Sweden)

    Jose eGonzalez-Vargas

    2015-09-01

    Full Text Available Humans can efficiently walk across a large variety of terrains and locomotion conditions with little or no mental effort. It has been hypothesized that the nervous system simplifies neuromuscular control by using muscle synergies, thus organizing multi-muscle activity into a small number of coordinative co-activation modules. In the present study we investigated how muscle modularity is structured across a large repertoire of locomotion conditions including five different speeds and five different ground elevations. For this we have used the non-negative matrix factorization technique in order to explain EMG experimental data with a low-dimensional set of four motor components. In this context each motor components is composed of a non-negative factor and the associated muscle weightings. Furthermore, we have investigated if the proposed descriptive analysis of muscle modularity could be translated into a predictive model that could: 1 Estimate how motor components modulate across locomotion speeds and ground elevations. This implies not only estimating the non-negative factors temporal characteristics, but also the associated muscle weighting variations. 2 Estimate how the resulting muscle excitations modulate across novel locomotion conditions and subjects.The results showed three major distinctive features of muscle modularity: 1 the number of motor components was preserved across all locomotion conditions, 2 the non-negative factors were consistent in shape and timing across all locomotion conditions, and 3 the muscle weightings were modulated as distinctive functions of locomotion speed and ground elevation. Results also showed that the developed predictive model was able to reproduce well the muscle modularity of un-modeled data, i.e. novel subjects and conditions. Muscle weightings were reconstructed with a cross-correlation factor greater than 70% and a root mean square error less than 0.10. Furthermore, the generated muscle excitations

  7. A predictive model of muscle excitations based on muscle modularity for a large repertoire of human locomotion conditions.

    Science.gov (United States)

    Gonzalez-Vargas, Jose; Sartori, Massimo; Dosen, Strahinja; Torricelli, Diego; Pons, Jose L; Farina, Dario

    2015-01-01

    Humans can efficiently walk across a large variety of terrains and locomotion conditions with little or no mental effort. It has been hypothesized that the nervous system simplifies neuromuscular control by using muscle synergies, thus organizing multi-muscle activity into a small number of coordinative co-activation modules. In the present study we investigated how muscle modularity is structured across a large repertoire of locomotion conditions including five different speeds and five different ground elevations. For this we have used the non-negative matrix factorization technique in order to explain EMG experimental data with a low-dimensional set of four motor components. In this context each motor components is composed of a non-negative factor and the associated muscle weightings. Furthermore, we have investigated if the proposed descriptive analysis of muscle modularity could be translated into a predictive model that could: (1) Estimate how motor components modulate across locomotion speeds and ground elevations. This implies not only estimating the non-negative factors temporal characteristics, but also the associated muscle weighting variations. (2) Estimate how the resulting muscle excitations modulate across novel locomotion conditions and subjects. The results showed three major distinctive features of muscle modularity: (1) the number of motor components was preserved across all locomotion conditions, (2) the non-negative factors were consistent in shape and timing across all locomotion conditions, and (3) the muscle weightings were modulated as distinctive functions of locomotion speed and ground elevation. Results also showed that the developed predictive model was able to reproduce well the muscle modularity of un-modeled data, i.e., novel subjects and conditions. Muscle weightings were reconstructed with a cross-correlation factor greater than 70% and a root mean square error less than 0.10. Furthermore, the generated muscle excitations matched

  8. Modulation between bilateral legs and within unilateral muscle synergists of postural muscle activity changes with development and aging.

    Science.gov (United States)

    Obata, Hiroki; Abe, Masaki O; Masani, Kei; Nakazawa, Kimitaka

    2014-01-01

    The effect of development and aging on common modulation between bilateral plantarflexors (i.e., the right and left soleus, and the right and left medial gastrocnemius) (bilateral comodulation) and within plantarflexors in one leg (i.e., the right soleus and the right medial gastrocnemius) (unilateral comodulation) was investigated during bipedal quiet standing by comparing electromyography-electromyography (EMG) coherence among three age groups: adult (23-35 years), child (6-8 years), and elderly (60-80 years). The results demonstrate that there was significant coherence between bilateral plantarflexors and within plantarflexors in one leg in the 0- to 4-Hz frequency region in all three age groups. Coherence in this frequency region was stronger in the elderly group than in the adult group, while no difference was found between the adult and child groups. Of particular interest was the finding of significant coherence in bilateral and unilateral EMG recordings in the 8- to 12-Hz frequency region in some subjects in the elderly group, whereas it was not observed in the adult and child groups. These results suggest that aging affects the organization of bilateral and unilateral postural muscle activities (i.e., bilateral and unilateral comodulation) in the plantarflexors during quiet standing.

  9. Effects of age and sex on neuromuscular-mechanical determinants of muscle strength.

    Science.gov (United States)

    Wu, Rui; Delahunt, Eamonn; Ditroilo, Massimiliano; Lowery, Madeleine; De Vito, Giuseppe

    2016-06-01

    The aim of this study was to concurrently assess the effect of age on neuromuscular and mechanical properties in 24 young (23.6 ± 3.7 years) and 20 older (66.5 ± 3.8 years) healthy males and females. Maximal strength of knee extensors (KE) and flexors (KF), contractile rate of torque development (RTD) and neural activation of agonist-antagonist muscles (surface EMG) were examined during maximal voluntary isometric contraction (MVIC). Tissue stiffness (i.e. musculo-articular stiffness (MAS) and muscle stiffness (MS)) was examined via the free-oscillation technique, whereas muscle architecture (MA) of the vastus lateralis and subcutaneous fat were measured by ultrasonography. Males exhibited a greater age-related decline for KE (47.4 %) and KF (53.1 %) MVIC, and RTD (60.4 %) when compared to females (32.9, 42.6 and 34.0 %, respectively). Neural activation of agonist muscles during KE MVIC falls markedly with ageing; however, no age and sex effects were observed in the antagonist co-activation. MAS and MS were lower in elderly compared with young participants and in females compared with males. Regarding MA, main effects for age (young 23.0 ± 3.3 vs older 19.5 ± 2.0 mm) and sex (males 22.4 ± 3.5 vs females 20.4 ± 2.7 mm) were detected in muscle thickness. For fascicle length, there was an effect of age (young 104.6 ± 8.8 vs older 89.8 ± 10.5 mm), while for pennation angle, there was an effect of sex (males 13.3 ± 2.4 vs females 11.5 ± 1.7°). These findings suggest that both neuromuscular and mechanical declines are important contributors to the age-related loss of muscle strength/function but with some peculiar sex-related differences.

  10. Reduced short-interval intracortical inhibition after eccentric muscle damage in human elbow flexor muscles.

    Science.gov (United States)

    Pitman, Bradley M; Semmler, John G

    2012-09-01

    The purpose of this study was to use paired-pulse transcranial magnetic stimulation (TMS) to examine the effect of eccentric exercise on short-interval intracortical inhibition (SICI) after damage to elbow flexor muscles. Nine young (22.5 ± 0.6 yr; mean ± SD) male subjects performed maximal eccentric exercise of the elbow flexor muscles until maximal voluntary contraction (MVC) force was reduced by ∼40%. TMS was performed before, 2 h after, and 2 days after exercise under Rest and Active (5% MVC) conditions with motor-evoked potentials (MEPs) recorded from the biceps brachii (BB) muscle. Peripheral electrical stimulation of the brachial plexus was used to assess maximal M-waves, and paired-pulse TMS with a 3-ms interstimulus interval was used to assess changes in SICI at each time point. The eccentric exercise resulted in a 34% decline in strength (P muscle strength (27%, P muscle soreness (P muscle damage. When the test MEP amplitudes were matched between sessions, we found that SICI was reduced by 27% in resting and 23% in active BB muscle 2 h after exercise. SICI recovered 2 days after exercise when muscle pain and soreness were present, suggesting that delayed onset muscle soreness from eccentric exercise does not influence SICI. The change in SICI observed 2 h after exercise suggests that eccentric muscle damage has widespread effects throughout the motor system that likely includes changes in motor cortex.

  11. Recognizing Age-Separated Face Images: Humans and Machines

    OpenAIRE

    Daksha Yadav; Richa Singh; Mayank Vatsa; Afzel Noore

    2014-01-01

    Humans utilize facial appearance, gender, expression, aging pattern, and other ancillary information to recognize individuals. It is interesting to observe how humans perceive facial age. Analyzing these properties can help in understanding the phenomenon of facial aging and incorporating the findings can help in designing effective algorithms. Such a study has two components - facial age estimation and age-separated face recognition. Age estimation involves predicting the age of an individua...

  12. Age-dependent uncoupling of mitochondria from Ca2+ release units in skeletal muscle

    Science.gov (United States)

    Ainbinder, Alina; Michelucci, Antonio; Kern, Helmut; Dirksen, Robert T.; Boncompagni, Simona; Protasi, Feliciano

    2015-01-01

    Calcium release units (CRUs) and mitochondria control myoplasmic [Ca2+] levels and ATP production in muscle, respectively. We recently reported that these two organelles are structurally connected by tethers, which promote proximity and proper Ca2+ signaling. Here we show that disposition, ultrastructure, and density of CRUs and mitochondria and their reciprocal association are compromised in muscle from aged mice. Specifically, the density of CRUs and mitochondria is decreased in muscle fibers from aged (>24 months) vs. adult (3-12 months), with an increased percentage of mitochondria being damaged and misplaced from their normal triadic position. A significant reduction in tether (13.8±0.4 vs. 5.5±0.3 tethers/100μm2) and CRU-mitochondrial pair density (37.4±0.8 vs. 27.0±0.7 pairs/100μm2) was also observed in aged mice. In addition, myoplasmic Ca2+ transient (1.68±0.08 vs 1.37±0.03) and mitochondrial Ca2+ uptake (9.6±0.050 vs 6.58±0.54) during repetitive high frequency tetanic stimulation were significantly decreased. Finally oxidative stress, assessed from levels of 3-nitrotyrosine (3-NT), Cu/Zn superoxide-dismutase (SOD1) and Mn superoxide dismutase (SOD2) expression, were significantly increased in aged mice. The reduced association between CRUs and mitochondria with aging may contribute to impaired cross-talk between the two organelles, possibly resulting in reduced efficiency in activity-dependent ATP production and, thus, to age-dependent decline of skeletal muscle performance. PMID:26485763

  13. Dietary proteins and amino acids in the control of the muscle mass during immobilization and aging: role of the MPS response.

    Science.gov (United States)

    Cholewa, Jason M; Dardevet, Dominique; Lima-Soares, Fernanda; de Araújo Pessôa, Kassiana; Oliveira, Paulo Henrique; Dos Santos Pinho, João Ricardo; Nicastro, Humberto; Xia, Zhi; Cabido, Christian Emmanuel Torres; Zanchi, Nelo Eidy

    2017-05-01

    response associated with protein ingestion. More research, however, is required to investigate if these nutrients translate to increases in MPS and, ultimately, increased lean mass in aging humans. The purpose of the present review is to discuss the role of protein/EAA intake to enhance postprandial MPS during conditions associated with muscle loss, and bring new perspectives and challenges associated nutritional interventions aimed to optimize the anabolic effects of dietary protein/EAAs ingestion.

  14. Muscle strength as a predictor of onset of ADL dependence in people aged 75 years

    DEFF Research Database (Denmark)

    Rantanen, Taina; Avlund, Kirsten; Suominen, Harri

    2002-01-01

    The aim of this prospective study over 5 years was to examine maximal isometric strength of multiple muscle groups as a predictor of losing independence in activities of daily living (ADL). The participants were from the Nordic Research on Aging (NORA75). These analyses are restricted to 567 people....... Of the 227 initially ADL independent men, 21 (9.3%) became dependent in ADL. In women, the figures were 30 (8.8%) of 340. Multiple logistic regression models were used to predict the risk of ADL dependence in groups based on strength tertiles. After confirming that the association of muscle strength...... dependent because of poor muscle strength, and who could reduce their risk by strengthening exercises....

  15. Transgenic overexpression of ADAM12 suppresses muscle regeneration and aggravates dystrophy in aged mdx mice

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Jensen, Charlotte Harken; Wewer, Ulla M;

    2007-01-01

    Muscular dystrophies are characterized by insufficient restoration and gradual replacement of the skeletal muscle by fat and connective tissue. ADAM12 has previously been shown to alleviate the pathology of young dystrophin-deficient mdx mice, a model for Duchenne muscular dystrophy. The observed...... effect of ADAM12 was suggested to be mediated via a membrane-stabilizing up-regulation of utrophin, alpha7B integrin, and dystroglycans. Ectopic ADAM12 expression in normal mouse skeletal muscle also improved regeneration after freeze injury, presumably by the same mechanism. Hence, it was suggested...... overexpressing ADAM12 (ADAM12(+)/mdx mice), even though their utrophin levels were mildly elevated compared with age-matched controls. Thus, membrane stabilization was not sufficient to provide protection during prolonged disease. Consequently, we reinvestigated skeletal muscle regeneration in ADAM12 transgenic...

  16. Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise

    DEFF Research Database (Denmark)

    Dela, Flemming; Mikines, K J; Larsen, J J

    1999-01-01

    clamp with a final 30 min of superimposed two-legged exercise at 70% of individual maximal heart rate. With superimposed exercise, leg glucose extraction decreased (P exercise, leg......Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle...... +/- 8, DM: 70 +/- 10 ml. min(-1). kg leg(-1)) compared with UT (H: 63 +/- 8, DM: 45 +/- 7 ml. min(-1). kg leg(-1)) but not different between groups (P > 0.05). From these results it can be concluded that, in both diabetic and healthy aged muscle, exercise adds to a maximally insulin-stimulated glucose...

  17. Melatonin and aging: prospects for human treatment.

    Science.gov (United States)

    Bubenik, G A; Konturek, S J

    2011-02-01

    Human life span, with or without modern medicine is around 85-95 years. All living creatures have their inner clock that measures their daily (circadian) and their seasonal (circannual) time. These time changes are mediated by the alteration of levels of melatonin, an evolutionary ancient hormone, which is produced in many body tissues, including the pineal gland, retina and the gastrointestinal tract (GIT). Light is blocking the production of melatonin in the pineal gland, darkness is stimulating it. So, the diurnal changes of light intensity of melatonin, provide a "daily clock" and the seasonal changes provide a "seasonal clock". Finally, the reduction of melatonin observed with aging, may indicate the presence of an "age clock". Melatonin is a strong antioxidant (often it is called scavenger of free radicals), which protects the body from the effects of noxious compounds. Therefore it was hypothesized that the reduction of melatonin levels with age contributes to the aging process. So far, the only remedy to extend the life span was a 40% reduction in caloric intake, which prolonged the life in mice, rats, dogs and monkeys by 30-50%. A large group of people imitate these experiments performed on animals, but the results of these experiments will not be known for several decades. How is being hungry prolonging the life span? There is a connection between caloric reduction and melatonin levels in GIT. Several experiments indicate that fasting in animals substantially increased their production of GIT melatonin. Therefore, instead of being permanently hungry, a prolongation of human life could be achieved by a replacement melatonin therapy. A daily intake of melatonin before bed time might achieve the same effect as fasting e.g. an increase of body melatonin levels, which will protect the individual from the ravages of old age. That includes Parkinson's disease and Alzheimer's disease. There is a large group of people taking melatonin daily who believe that

  18. Aging, human immunodeficiency virus, and bone health

    Directory of Open Access Journals (Sweden)

    Kim C Mansky

    2010-09-01

    Full Text Available Kim C ManskyDivision of Orthodontics, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USAAbstract: Highly active antiretroviral therapy (HAART has had a profound impact on improving the long-term prognosis for individuals infected with human immunodeficiency virus (HIV. HAART has been available for close to two decades, and now a significant number of patients with access to HAART are over the age of 50 years. Many clinical studies have indicated that HIV infection, as well as components of HAART, can increase the risk in these individuals to a variety of noninfectious complications, including a risk to bone health. There is a significant need for detailed mechanistic analysis of the aging, HIV-infected population regarding the risk of HIV infection and therapy in order to maintain bone health. Insights from basic mechanistic studies will help to shed light on the role of HIV infection and the components of HAART that impact bone health, and will help in identifying preventative countermeasures, particularly for individuals 50 years of age and older.Keywords: osteopenia, osteomalacia, osteoporosis, bisphosphonates, tenofovir, osteoimmunology

  19. The immune system in the aging human.

    Science.gov (United States)

    Rymkiewicz, Paulina Dominika; Heng, Yi Xiong; Vasudev, Anusha; Larbi, Anis

    2012-09-01

    With the improvement of medical care and hygienic conditions, there has been a tremendous increment in human lifespan. However, many of the elderly (>65 years) display chronic illnesses, and a majority requires frequent and longer hospitalization. The robustness of the immune system to eliminate or control infections is often eroded with advancing age. Nevertheless, some elderly individuals do cope better than others. The origin of these inter-individual differences may come from genetic, lifestyle conditions (nutrition, socio-economic parameters), as well as the type, number and recurrence of pathogens encountered during life. The theory we are supporting is that chronic infections, through life, will induce profound changes in the immune system probably due to unbalanced inflammatory profiles. Persistent viruses such a cytomegalovirus are not eliminated and are a driven force to immune exhaustion. Because of their age, elderly individuals may have seen more of these chronic stimulators and have experienced more reactivation episodes ultimately leading to shrinkage of their repertoire and overall immune robustness. This review integrates updates on immunity with advancing age and its impact on associated clinical conditions.

  20. No release of interstitial glutamate in experimental human model of muscle pain

    DEFF Research Database (Denmark)

    Ashina, M.; Jørgensen, M.; Stallknecht, Bente;

    2005-01-01

    Glutamate may be released from muscle nociceptors and thereby contribute to mechanisms underlying acute and chronic muscle pain. In vivo concentration of glutamate during muscle pain has not previously been studied in either animals or humans. In the present study, we aimed to study the in vivo...... flow increased significantly over time in response to infusion of chemical mixture and placebo (p = 0.001). However, we found no difference in changes in muscle blood flow between chemical mixture and placebo (p > 0.05). In conclusion, the present study demonstrates no signs of increased release...... of glutamate from myofascial nociceptors during and after acute experimentally induced muscle pain and tenderness....

  1. The exercise-induced stress response of skeletal muscle, with specific emphasis on humans.

    Science.gov (United States)

    Morton, James P; Kayani, Anna C; McArdle, Anne; Drust, Barry

    2009-01-01

    Skeletal muscle adapts to the stress of contractile activity via changes in gene expression to yield an increased content of a family of highly conserved cytoprotective proteins known as heat shock proteins (HSPs). These proteins function to maintain homeostasis, facilitate repair from injury and provide protection against future insults. The study of the exercise-induced production of HSPs in skeletal muscle is important for the exercise scientist as it may provide a valuable insight into the molecular mechanisms by which regular exercise can provide increased protection against related and non-related stressors. As molecular chaperones, HSPs are also fundamental in facilitating the cellular remodelling processes inherent to the training response. Whilst the exercise-induced stress response of rodent skeletal muscle is relatively well characterized, data from humans are more infrequent and less insightful. Data indicate that acute endurance- and resistance-type exercise protocols increase the muscle content of ubiquitin, alphaB-crystallin, HSP27, HSP60, HSC70 and HSP70. Although increased HSP transcription occurs during exercise, immediately post-exercise or several hours following exercise, time-course studies using western blotting techniques have typically demonstrated a significant increase in protein content is only detectable within 1-2 days following the exercise stress. However, comparison amongst studies is complicated by variations in exercise protocol (mode, intensity, duration, damaging, non-damaging), muscle group examined, predominant HSP measured and, perhaps most importantly, differences in subject characteristics both within and between studies (training status, recent activity levels, nutritional status, age, sex, etc.). Following 'non-damaging' endurance-type activities (exercise that induces no overt structural and functional damage to the muscle), the stress response is thought to be mediated by redox signalling (transient and reversible

  2. Masticatory muscles in the muscular dystrophic mouse. Aspects of the age-related progression of the disease

    DEFF Research Database (Denmark)

    Vilmann, H; Kirkeby, S

    1988-01-01

    Cross-sections of normal and dystrophic digastric and masseter muscles from 7- and 35- to 40-week-old mice were studied in the light microscope. Comparisons of mean cell size, cell size variance and number of centrally positioned nuclei in a given number of fibers were carried out. The masseter m...... muscle seems at both ages to be far more affected by the disease than the digastric muscle. However, the progression of the disease from 7 to 40 weeks is more pronounced in the digastric muscle than in the masseter muscle....

  3. Sports Mass Age Therapy on the Reduction of Delayed Onset Muscle Soreness of the Quadriceps Femoris

    Directory of Open Access Journals (Sweden)

    Boguszewski Dariusz

    2014-12-01

    Full Text Available Purpose. Massage therapy is one of most commonly applied treatments during athletic training. The aim of this study was to assess the effectiveness of sports massage therapy on reducing post-exercise quadriceps muscle soreness. Methods. A sample of 29 women aged 24-26 years was divided into an experimental group (n = 15 receiving classic sports massage therapy and a control group (n = 14 given no treatment. An exercise session consisting of five sets of deep squat jumps was administered after which lower limb power as assessed via the vertical jump test. Muscle soreness was assessed using the visual analogue scale (VAS and exercise intensity with the Borg Rating of Perceived Exertion Scale. Subsequent measurements of lower limb power and muscle soreness were performed 24, 48, 72 and 96 h after the exercise session. Differences between the measurements were assessed by the Friedman and least significant difference tests while between-group comparisons involved the Mann-Whitney U test. Results. The largest decrease in lower limb power was observed between the first measurement after the exercise session and 24 h later (p < 0.01. The smallest decrease in power was observed in the massage group. The highest levels of muscle soreness were noted 24 h post-exercise in the massage group and 48 h post-exercise in the control group. The experimental group showed a decrease in muscle soreness in each subsequent measurement, with the results close to zero on the VAS 96 h postexercise. Conclusions. Massage therapy quickened recovery and improved muscle efficiency post-exercise and may serve as an effective treatment of muscle soreness. The analgesic effect of massage suggests it should be widely applied in sport, physical therapy and rehabilitation.

  4. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition

    DEFF Research Database (Denmark)

    Nielsen, Anders Rinnov; Mounier, Remi; Plomgaard, Peter

    2007-01-01

    of recovery without any changes in muscle IL-15 protein content or plasma IL-15 at any of the investigated time points. In conclusion, IL-15 mRNA level is enhanced in skeletal muscles dominated by type 2 fibres and resistance exercise induces increased muscular IL-15 mRNA levels. IL-15 mRNA levels in skeletal......The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus...... lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers (n = 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects (n = 8) not involved...

  5. Muscle quality, but not muscle thickness, is decreased in different age groups of active older women

    Directory of Open Access Journals (Sweden)

    Anthony Bouillod

    2015-05-01

    Full Text Available The aim of this study was to assess the accuracy of the Suunto Memory Belt (SMB heart rate (HR recorder compared with that of a standard electrocardiogram system (ECG and compared the heart rate variability (HRV analyses conducted with each dataset. Heart rate was simultaneously recorded using ECG and SMB in fifteen participants [mean (SD age 27.3 (13.9 years, height 177.4 (10.2 cm and body mass 66.8 (15.3 kg] during an orthostatic tilt test. The two datasets were analysed to compare the number and type of R-R interval artefacts and indices from HRV (RMSSD, pNN50, HF, LF, SD1, and SD2. For artefact detection, 16,742 R-R intervals were analysed during all recordings. Only 18 artefacts, 9 type 1 (long R-R interval and 9 type 2 (short R-R interval, were identified with the SMB. Bland-Altman analysis indicated excellent accuracy for the SMB, with limits of agreement of -2.00 and +1.94 ms. Further, the reference and SMB systems were strongly correlated. The similarity between each device indicated that the SMB could reliably record R-R intervals.

  6. Stretch-shortening cycle muscle power in women and men aged 18-81 years: Influence of age and gender.

    Science.gov (United States)

    Edwén, C E; Thorlund, J B; Magnusson, S P; Slinde, F; Svantesson, U; Hulthén, L; Aagaard, P

    2014-08-01

    This study explored the age-related deterioration in stretch-shortening cycle (SSC) muscle power and concurrent force-velocity properties in women and men across the adult life span. A total of 315 participants (women: n = 188; men: n = 127) aged 18-81 years performed maximal countermovement jumps on an instrumented force plate. Maximal SSC leg extension power expressed per kg body mass (Ppeak) was greater in men than in women across the adult age span (P < 0.001); however, this gender difference was progressively reduced with increasing age, because men showed an ∼50% faster rate of decline in SSC power than women (P < 0.001). Velocity at peak power (VPpeak) was greater in men than in women (P < 0.001) but declined at a greater rate in men than in women (P = 0.002). Vertical ground reaction force at peak power (FPpeak) was higher in men than in women in younger adults only (P < 0.001) and the age-related decline was steeper in men than in women (P < 0.001). Men demonstrated a steeper rate of decline in Ppeak than women with progressive aging. This novel finding emerged as a result of greater age-related losses in men for both force and velocity. Consequently, maximal SSC power production was observed to converge between genders when approaching old age.

  7. Effects of ageing on expression of the muscle-specific E3 ubiquitin ligases and Akt-dependent regulation of Foxo transcription factors in skeletal muscle.

    Science.gov (United States)

    Wagatsuma, Akira; Shiozuka, Masataka; Takayama, Yuzo; Hoshino, Takayuki; Mabuchi, Kunihiko; Matsuda, Ryoichi

    2016-01-01

    Controversy exists as to whether the muscle-specific E3 ubiquitin ligases MAFbx and MuRF1 are transcriptionally upregulated in the process of sarcopenia. In the present study, we investigated the effects of ageing on mRNA/protein expression of muscle-specific E3 ubiquitin ligases and Akt/Foxo signalling in gastrocnemius muscles of female mice. Old mice exhibited a typical sarcopenic phenotype, characterized by loss of muscle mass and strength, decreased amount of myofibrillar proteins, incidence of aberrant muscle fibres, and genetic signature to sarcopenia. Activation levels of Akt were lower in adult and old mice than in young mice. Consequently, Akt-mediated phosphorylation levels of Foxo1 and Foxo3 proteins were decreased. Nuclear levels of Foxo1 and Foxo3 proteins showed an overall increasing trend in old mice. MAFbx mRNA expression was decreased in old mice relative to adult mice, whereas MuRF1 mRNA expression was less affected by ageing. At the protein level, MAFbx was less affected by ageing, whereas MuRF1 was increased in old mice relative to adult mice, with ubiquitin-protein conjugates being increased with ageing. In conclusion, we provided evidence for no mRNA upregulation of muscle-specific E3 ubiquitin ligases and disconnection between their expression and Akt/Foxo signalling in sarcopenic mice. Their different responsiveness to ageing may reflect different roles in sarcopenia.

  8. AGE WISE HISTOMORPHOLOGICAL CHANGES IN HUMAN LIVER

    Directory of Open Access Journals (Sweden)

    Tribeni

    2015-11-01

    Full Text Available CONTEXT: Hepato cellular carcinoma (HCC results in between 2.5 lakhs to 1million deaths globally per annum. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure. AIMS: Keeping this concept in view, a study was conducted in the Guwahati Zone of Northeast India, to compare the histomorphological features of the human liver in different age groups. SETTING AND DESIGN: Apparently healthy livers were obtained from 21 subjects on whom medicolegal post-mortems had been performed. Their ages varied from newborn to 90 years. Subjects were divided into 3 groups. 7 specimens were taken from each group. (1 Pediatric (2 Adult (3 Old age. METHODS AND MATERIALS: In all the above age groups, immediately after removal of the livers, they were washed in normal saline, dried with blotting paper and weighed in an electronic weighing machine. Sections of liver were fixed, processed, cut and stained with Harris Haematoxylin and Eosin stain. RESULTS: The liver loses weight from 50 years onwards. There appears to be racial and environmental differences in the change in liver weight in old age. Autopsy studies show a diminution of nearly 46% in liver weight between the 3rd and 10th decades of life. The liver decreases in size with age. The hepatocytes are radially disposed in the liver lobule. They are piled up, forming a layer one cell thick (except in young children in a fashion similar to the bricks of a wall. These plates are directed from the periphery of the lobule to its centre and anastomose freely forming a complex labyrinthine and sponge-like structure. CONCLUSIONS: From the findings in the present study it can be concluded that: 1. Nowadays, the measurement of liver volume has gained practical use in relation to liver transplantation. 2. We have compared the histomorphology of adult liver with a child. The findings in both the groups are very similar. This feature is important, since in

  9. Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application.

    Science.gov (United States)

    Sinha, Sanjay; Iyer, Dharini; Granata, Alessandra

    2014-06-01

    Vascular smooth muscle cells (SMCs) arise from multiple origins during development, raising the possibility that differences in embryological origins between SMCs could contribute to site-specific localization of vascular diseases. In this review, we first examine the developmental pathways and embryological origins of vascular SMCs and then discuss in vitro strategies for deriving SMCs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We then review in detail the potential for vascular disease modeling using iPSC-derived SMCs and consider the pathological implications of heterogeneous embryonic origins. Finally, we touch upon the role of human ESC-derived SMCs in therapeutic revascularization and the challenges remaining before regenerative medicine using ESC- or iPSC-derived cells comes of age.

  10. Alterations in intrinsic mitochondrial function with aging are fiber type-specific and do not explain differential atrophy between muscles.

    Science.gov (United States)

    Picard, Martin; Ritchie, Darmyn; Thomas, Melissa M; Wright, Kathryn J; Hepple, Russell T

    2011-12-01

    To determine whether mitochondrial dysfunction is causally related to muscle atrophy with aging, we examined respiratory capacity, H(2) O(2) emission, and function of the mitochondrial permeability transition pore (mPTP) in permeabilized myofibers prepared from four rat muscles that span a range of fiber type and degree of age-related atrophy. Muscle atrophy with aging was greatest in fast-twitch gastrocnemius (Gas) muscle (-38%), intermediate in both the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscles (-21%), and non-existent in adductor longus (AL) muscle (+47%). In contrast, indices of mitochondrial dysfunction did not correspond to this differential degree of atrophy. Specifically, despite higher protein expression for oxidative phosphorylation (oxphos) system in fast Gas and EDL, state III respiratory capacity per myofiber wet weight was unchanged with aging, whereas the slow Sol showed proportional decreases in oxphos protein, citrate synthase activity, and state III respiration. Free radical leak (H(2) O(2) emission per O(2) flux) under state III respiration was higher with aging in the fast Gas, whereas state II free radical leak was higher in the slow AL. Only the fast muscles had impaired mPTP function with aging, with lower mitochondrial calcium retention capacity in EDL and shorter time to mPTP opening in Gas and EDL. Collectively, our results underscore that the age-related changes in muscle mitochondrial function depend largely upon fiber type and are unrelated to the severity of muscle atrophy, suggesting that intrinsic changes in mitochondrial function are unlikely to be causally involved in aging muscle atrophy. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  11. FES Training in Aging: interim results show statistically significant improvements in mobility and muscle fiber size

    Directory of Open Access Journals (Sweden)

    Helmut Kern

    2012-03-01

    Full Text Available Aging is a multifactorial process that is characterized by decline in muscle mass and performance. Several factors, including reduced exercise, poor nutrition and modified hormonal metabolism, are responsible for changes in the rates of protein synthesis and degradation that drive skeletal muscle mass reduction with a consequent decline of force generation and mobility functional performances. Seniors with normal life style were enrolled: two groups in Vienna (n=32 and two groups in Bratislava: (n=19. All subjects were healthy and declared not to have any specific physical/disease problems. The two Vienna groups of seniors exercised for 10 weeks with two different types of training (leg press at the hospital or home-based functional electrical stimulation, h-b FES. Demografic data (age, height and weight were recorded before and after the training period and before and after the training period the patients were submitted to mobility functional analyses and muscle biopsies. The mobility functional analyses were: 1. gait speed (10m test fastest speed, in m/s; 2. time which the subject needed to rise from a chair for five times (5x Chair-Rise, in s; 3. Timed –Up-Go- Test, in s; 4. Stair-Test, in s; 5. isometric measurement of quadriceps force (Torque/kg, in Nm/kg; and 6. Dynamic Balance in mm. Preliminary analyses of muscle biopsies from quadriceps in some of the Vienna and Bratislava patients present morphometric results consistent with their functional behaviors. The statistically significant improvements in functional testings here reported demonstrates the effectiveness of h-b FES, and strongly support h-b FES, as a safe home-based method to improve contractility and performances of ageing muscles.

  12. Muscle metabolism changes with age and maturation: How do they relate to youth sport performance?

    Science.gov (United States)

    Armstrong, Neil; Barker, Alan R; McManus, Alison M

    2015-07-01

    To provide an evidence-based review of muscle metabolism changes with sex-, age- and maturation with reference to the development of youth sport performance. A narrative review of data from both invasive and non-invasive studies, from 1970 to 2015, founded on personal databases supported with computer searches of PubMed and Google Scholar. Youth sport performance is underpinned by sex-, age- and maturation-related changes in muscle metabolism. Investigations of muscle size, structure and metabolism; substrate utilisation; pulmonary oxygen uptake kinetics; muscle phosphocreatine kinetics; peak anaerobic and aerobic performance; and fatigue resistance; determined using a range of conventional and emerging techniques present a consistent picture. Age-related changes have been consistently documented but specific and independent maturation-related effects on muscle metabolism during exercise have proved elusive to establish. Children are better equipped for exercise supported primarily by oxidative metabolism than by anaerobic metabolism. Sexual dimorphism is apparent in several physiological variables underpinning youth sport performance. As young people mature there is a progressive but asynchronous transition into an adult metabolic profile. The application of recent developments in technology to the laboratory study of the exercising child and adolescent has both supplemented existing knowledge and provided novel insights into developmental exercise physiology. A sound foundation of laboratory-based knowledge has been established but the lack of rigorously designed child-specific and sport-specific testing environments has clouded the interpretation of the data in real life situations. The primary challenge remains the translation of laboratory research into the optimisation of youth sports participation and performance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Models of Accelerated Sarcopenia: Critical Pieces for Solving the Puzzle of Age-Related Muscle Atrophy

    Science.gov (United States)

    Buford, Thomas W.; Anton, Stephen D.; Judge, Andrew R.; Marzetti, Emanuele; Wohlgemuth, Stephanie E; Carter, Christy S.; Leeuwenburgh, Christiaan; Pahor, Marco; Manini, Todd M.

    2013-01-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia. PMID:20438881

  14. Suction-modified needle biopsy technique for the human soleus muscle.

    Science.gov (United States)

    Cotter, Joshua A; Yu, Alvin; Kreitenberg, Arthur; Haddad, Fadia H; Baker, Michael J; Fox, John C; Adams, Gregory R

    2013-10-01

    The needle biopsy technique for the soleus muscle is of particular interest because of the muscle's unique fiber type distribution, contractile properties, and sensitivity to unloading. Unlike other commonly biopsied muscles, the soleus is not fully superficial and is in close proximity to neurovascular structures, resulting in a more challenging biopsy. Because of this, a standardized protocol for performing needle biopsies on the human soleus muscle that is safe, reliable, and repeatable is presented. Ultrasonography was used on an initial set of 12 subjects to determine the optimal biopsy zone, thereby guiding the location of the incision site. There were 45 subjects recruited who attended 2 separate biopsy sessions. Each biopsy session incorporated 3 passes of the biopsy needle proximal, posterior, and distal using suction from a portable vacuum source producing 3 separate muscle specimens. There were 84 soleus muscle biopsy procedures which were successfully conducted yielding 252 total samples without complication. Ultrasonography was used to confirm biopsy needle infiltration of the soleus muscle. Average sample weight obtained per pass was 61.5 +/- 15.7 mg. Histochemistry and molecular analyses demonstrated a considerably higher amount of slow type I MHC in comparison to the vastus lateralis, providing verification for the successful sampling of the soleus muscle. The procedure presented consists of a detailed protocol to accurately and consistently obtain muscle biopsy samples from the human soleus muscle. We have demonstrated that the human soleus biopsy is a safe, reliable, and repeatable procedure providing ample tissue for multiple types of analyses.

  15. Efflux of creatine kinase from isolated soleus muscle depends on age, sex and type of exercise in mice.

    Science.gov (United States)

    Baltusnikas, Juozas; Venckunas, Tomas; Kilikevicius, Audrius; Fokin, Andrej; Ratkevicius, Aivaras

    2015-06-01

    Elevated plasma creatine kinase (CK) activity is often used as an indicator of exercise-induced muscle damage. Our aim was to study effects of contraction type, sex and age on CK efflux from isolated skeletal muscles of mice. The soleus muscle (SOL) of adult (7.5-month old) female C57BL/6J mice was subjected to either 100 passive stretches, isometric contractions or eccentric contractions, and muscle CK efflux was assessed after two-hour incubation in vitro. SOL of young (3-month old) male and female mice was studied after 100 eccentric contractions. For adult females, muscle CK efflux was larger (p resistance to exercise-induced CK efflux depends on age and sex of mice. Key pointsMuscle lengthening contractions induce the highest CK efflux in vitro compared with similar protocol of isometric contractions or passive stretches.Muscle CK efflux in vitro is applicable in studying changes of sarcolemma permeability/integrity, a proxy of muscle damage, in response to muscle contractile activity.Isolated muscle resistance to exercise-induced CK efflux is greater in female compared to male mice of young age and is further increased in adult female mice.

  16. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure

    DEFF Research Database (Denmark)

    Aagaard, P; Suetta, C; Caserotti, P

    2010-01-01

    to elicit effective countermeasures in elderly individuals even at a very old age (>80 years) by evoking muscle hypertrophy along with substantial changes in neuromuscular function, respectively. Notably, the training-induced changes in muscle mass and nervous system function leads to an improved functional......Aging is characterized by loss of spinal motor neurons (MNs) due to apoptosis, reduced insulin-like growth factor I signaling, elevated amounts of circulating cytokines, and increased cell oxidative stress. The age-related loss of spinal MNs is paralleled by a reduction in muscle fiber number...... and size (sarcopenia), resulting in impaired mechanical muscle performance that in turn leads to a reduced functional capacity during everyday tasks. Concurrently, maximum muscle strength, power, and rate of force development are decreased with aging, even in highly trained master athletes. The impairment...

  17. Observation of Age-Related Decline in the Performance of the Transverse Abdominis Muscle.

    Science.gov (United States)

    Davies, Paul; Grace, Fergal M; Lewis, Mark P; Sculthorpe, Nicholas

    2016-01-01

    Previous research has shown that the performance of skeletal muscle declines with advancing age. Coordination of the transverse abdominis (TrA), a deep postural muscle, has been shown to be reduced in persons with low back pain. No previous research has studied the effect of age on the activation on this muscle. To assess the effect of age on TrA activation in response to rapid arm abduction. Cross-sectional cohort study. University exercise physiology laboratory. A total of 18 adult men (aged 27 ± 7.0 years) for the younger group and 11 older adults (5 men and 6 women, aged 59.6 ± 4.0 years) were recruited for this study. Participants were positioned on a treatment table and performed a series of rapid arm abduction movements with their right arm while the activation of the TrA muscle was recorded using ultrasound imaging. Onset of arm abduction was measured using surface electromyography and synchronized with the ultrasound through the ultrasound unit's electrocardiogram channel. The mean time difference between the 2 events was calculated during post-hoc analysis. A Mann-Whitney test was performed to test for differences in the onset performance of the TrA muscle between the 2 groups. Results showed that the older group was significantly slower than the younger group in engaging their TrA in response to the rapid arm abduction (P = .036). A separate analysis of the older group data showed that no significant differences existed between the male and female participants that could potentially have acted as a confounding factor for the main finding (P = .126). This study shows that older adults were slower than younger adults in activating their TrA muscle in response to rapid arm abduction. This delay has the potential to lead to increased occasions when the low back is unprotected, increasing the likelihood of injury or low back pain. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  18. Heparin inhibits human coronary artery smooth muscle cell migration.

    Science.gov (United States)

    Kohno, M; Yokokawa, K; Yasunari, K; Minami, M; Kano, H; Mandal, A K; Yoshikawa, J

    1998-09-01

    Heparin, an anticoagulant, has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies, but the clinical trials of heparin in coronary balloon angioplasty have been negative. The current study, therefore, examined the effect of heparin on basal or stimulated migration by serum and platelet-derived growth factor (PDGF)-BB in cultured human coronary artery smooth muscle cells (SMCs) by Boyden's chamber method. In addition, the reversibility of the heparin effect on human coronary artery SMC migration was examined. Fetal calf serum (FCS) and PDGF-BB stimulated SMC migration in a concentration-dependent manner. Heparin in moderate to high concentration (10 to 100 U/mL) exhibited concentration-related inhibition of FCS- and PDGF-BB-stimulated SMC migration; however, a low concentration (1 U/mL) of heparin had no inhibitory effects. Heparin also had weak inhibitory effects on nonstimulated SMC migration. The SMCs that were exposed to a high concentration (100 U/mL) of heparin for 6 hours were capable of migrating after a short lag period of removal of heparin from the culture medium. These SMCs also showed recovery of responses to FCS and PDGF-BB by migrating significantly greater than the nonstimulated level. Furthermore, heparin-containing medium did not contain detached cells. These results indicate that heparin inhibits human coronary artery SMC migration, especially when stimulated by FCS or PDGF-BB, and that this inhibitory effect of heparin is reversible and not simply a function of killing cells.

  19. Task-dependent spatial distribution of neural activation pattern in human rectus femoris muscle.

    Science.gov (United States)

    Watanabe, Kohei; Kouzaki, Motoki; Moritani, Toshio

    2012-04-01

    Compartmentalization of skeletal muscle by multiple motor nerve branches, named as neuromuscular compartment (NMC), has been demonstrated in animals as well as humans. While different functional roles among individual NMCs were reported in the animal studies, no studies have clarified the region-specific functional role within a muscle related with NMCs arrangement in human skeletal muscle. It was reported that the rectus femoris (RF) muscle is innervated by two nerve branches attached at proximal and distal parts of the muscle. The purpose of the present study is to clarify the possible region-specific functional role in the human RF muscle. Multi-channel surface electromyography (SEMG) were recorded from the RF muscle by using 128 electrodes during two different submaximal isometric contractions that the muscle contributes, i.e. isometric knee extension and hip flexion, at 20%, 40%, 60% and 80% of maximal voluntary contraction (MVC). Results indicated that the central locus activation for the amplitude map of SEMG during hip flexion located at more proximal region compared with that during knee extension. Significant higher normalized root mean square (RMS) values were observed at the proximal region during the hip flexion in comparison to those at middle and distal regions at 60% and 80% of MVC (pMVC (p<0.05). The results of the present study suggest possible region-specific functional role in the human RF muscle.

  20. Ultrastructural features of skeletal muscle in adult and aging Ts65Dn mice, a murine model of Down syndrome.

    Science.gov (United States)

    Cisterna, Barbara; Costanzo, Manuela; Scherini, Elda; Zancanaro, Carlo; Malatesta, Manuela

    2013-10-01

    Patients with Down syndrome (DS) suffer from muscle hypotonia and an altered motor coordination whose basic mechanisms are still largely unknown. Interestingly, they show muscle weakness like healthy aged subjects, suggesting possible similarity with sarcopenia: to test this hypothesis, the Ts65Dn mouse, a suitable animal model of DS, was employed. The fine structure of skeletal fibres of the quadriceps femoris muscle was analysed in adult (12 months) and aging (19 months) animals and their age-matched euploid controls by combining morphometry and immunocytochemistry at transmission electron microscopy. Results demonstrated structural alterations of mitochondria and myonuclei reminiscent of those observed in age-related sarcopenia, supporting the hypothesis that trisomy leads to an early aging of skeletal muscle consistent with the multi-systemic premature aging typical of DS.

  1. Impaired mitochondrial degradation by autophagy in the skeletal muscle of the aged female interleukin 10 null mouse.

    Science.gov (United States)

    Ko, Fred; Abadir, Peter; Marx, Ruth; Westbrook, Reyhan; Cooke, Carol; Yang, Huanle; Walston, Jeremy

    2016-01-01

    Mitochondrial dysfunction, chronic inflammation and muscle aging are closely linked. Mitochondrial clearance is a process to dampen inflammation and is a critical pre-requisite to mitobiogenesis. The combined effect of aging and chronic inflammation on mitochondrial degradation by autophagy is understudied. In interleukin 10 null mouse (IL-10(tm/tm)), a rodent model of chronic inflammation, we studied the effects of aging and inflammation on mitochondrial clearance. We show that aging in IL-10(tm/tm) is associated with reduced skeletal muscle mitochondrial death signaling and altered formation of autophagosomes, compared to age-matched C57BL/6 controls. Moreover, skeletal muscles of old IL-10(tm/tm) mice have the highest levels of damaged mitochondria with disrupted mitochondrial ultrastructure and autophagosomes compared to all other groups. These observations highlight the interface between chronic inflammation and aging on altered mitochondrial biology in skeletal muscles.

  2. Age Related Differences in the Surface EMG Signals on Adolescent's Muscle during Contraction

    Science.gov (United States)

    Uddin Ahamed, Nizam; Taha, Zahari; Alqahtani, Mahdi; Altwijri, Omar; Rahman, Matiur; Deboucha, Abdelhakim

    2016-02-01

    The aim of this study was to investigate whether there are differences in the amplitude of the EMG signal among five different age groups of adolescent's muscle. Fifteen healthy adolescents participated in this study and they were divided into five age groups (13, 14, 15, 16 and 17 years). Subjects were performed dynamic contraction during lifting a standard weight (3-kg dumbbell) and EMG signals were recorded from their Biceps Brachii (BB) muscle. Two common EMG analysis techniques namely root mean square (RMS) and mean absolute values (MAV) were used to find the differences. The statistical analysis was included: linear regression to examine the relationships between EMG amplitude and age, repeated measures ANOVA to assess differences among the variables, and finally Coefficient of Variation (CoV) for signal steadiness among the groups of subjects during contraction. The result from RMS and MAV analysis shows that the 17-years age groups exhibited higher activity (0.28 and 0.19 mV respectively) compare to other groups (13-Years: 0.26 and 0.17 mV, 14-years: 0.25 and 0.23 mV, 15-Years: 0.23 and 0.16 mV, 16-years: 0.23 and 0.16 mV respectively). Also, this study shows modest correlation between age and signal activities among all age group's muscle. The experiential results can play a pivotal role for developing EMG prosthetic hand controller, neuromuscular system, EMG based rehabilitation aid and movement biomechanics, which may help to separate age groups among the adolescents.

  3. Dysregulation of SIRT-1 in aging mice increases skeletal muscle fatigue by a PARP-1-dependent mechanism.

    Science.gov (United States)

    Mohamed, Junaith S; Wilson, Joseph C; Myers, Matthew J; Sisson, Kayla J; Alway, Stephen E

    2014-10-01

    Accumulation of reactive oxygen species (ROS) in skeletal muscles and the resulting decline in muscle performance are hallmarks of sarcopenia. However, the precise mechanism by which ROS results in a decline in muscle performance is unclear. We demonstrate that isometric-exercise concomitantly increases the activities of Silent information regulator 1 (SIRT-1) and Poly [ADP-ribose] polymerase (PARP-1), and that activated SIRT-1 physically binds with and inhibits PARP-1 activity by a deacetylation dependent mechanism in skeletal muscle from young mice. In contrast, skeletal muscle from aged mice displays higher PARP-1 activity and lower SIRT-1 activity due to decreased intracellular NAD+ content, and as a result reduced muscle performance in response to exercise. Interestingly, injection of PJ34, a PARP-1 inhibitor, in aged mice increased SIRT-1 activity by preserving intracellular NAD+ content, which resulted in higher skeletal muscle mitochondrial biogenesis and performance. We found that the higher activity of PARP-1 in H2O2-treated myotubes or in exercised-skeletal muscles from aged mice is due to an elevated level of PARP-1 acetylation by the histone acetyltransferase General control of amino acid synthesis protein 5-like 2 (GCN-5). These results suggest that activation of SIRT-1 and/or inhibition of PARP-1 may ameliorate skeletal muscle performance in pathophysiological conditions such as sarcopenia and disuse-induced atrophy in aging.

  4. Muscle triacylglycerol and hormone-sensitive lipase activity in untrained and trained human muscles

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Biba, Taus O; Galbo, Henrik

    2006-01-01

    During exercise, triacylglycerol (TG) is recruited in skeletal muscles. We hypothesized that both muscle hormone-sensitive lipase (HSL) activity and TG recruitment would be higher in trained than in untrained subjects in response to prolonged exercise. Healthy male subjects (26 +/- 1 years, body ...

  5. SUPERNORMAL MUSCLE-FIBER CONDUCTION-VELOCITY DURING INTERMITTENT ISOMETRIC-EXERCISE IN HUMAN MUSCLE

    NARCIS (Netherlands)

    VANDERHOEVEN, JH; LANGE, F

    1994-01-01

    Muscle fiber conduction velocity (MFCV) and surface electromyographic parameters were studied in the brachial biceps muscle of healthy males during voluntary intermittent isometric contractions at 50% of maximum force. Recovery in the following 15 min was then observed. The measurements were perform

  6. Provocation of delayed-onset muscle soreness in the human jaw-closing muscles

    NARCIS (Netherlands)

    Türker, K.S.; Koutris, M.; Sümer, N.C.; Atis, E.S.; Linke, I.R.; Lobbezoo, F.; Naeije, M.

    2010-01-01

    Eccentric contractions of jaw-closing muscles are difficult to perform. This may explain why fatigue-inducing experiments performed so far suggest the jaw-closing muscles to be fatigue resistant. Aim of this study was to construct an apparatus that can impose intense eccentric contractions to the ja

  7. Resveratrol modulates the angiogenic response to exercise training in skeletal muscle of aged men

    DEFF Research Database (Denmark)

    Gliemann Hybholt, Lasse; Olesen, Jesper; Biensø, Rasmus S

    2014-01-01

    Aim: The polyphenol resveratrol has in animal studies been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Methods: Forty-three healthy...... physically inactive aged men (65±1 years) were divided into A) a training group that conducted 8 weeks of intense exercise training where half of the subjects received a daily intake of either 250 mg trans resveratrol (n=14) and the other half received placebo (n=13); and B) a non-training group...... that received either 250 mg trans resveratrol (n=9) or placebo (n=7). Results: The group that trained with placebo showed a ~20% increase in capillary to fiber (C:F) ratio, an increase in the muscle protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2, and tissue inhibitor of matrix...

  8. Testosterone therapy preserves muscle strength and power in aging men with type 2 diabete

    DEFF Research Database (Denmark)

    Magnussen, L V; Hvid, L G; Hermann, A P

    2017-01-01

    The purpose of the study was to evaluate whether testosterone replacement therapy improves muscle mechanical and physical function in addition to increasing lean leg mass and total lean body mass in aging men with type 2 diabetes and lowered bio-available testosterone (BioT) levels. Thirty-nine men...... aged 50-70 years with type 2 diabetes and BioT levels testosterone gel (testosterone replacement therapy, n = 20) or placebo (n = 19) for 24 weeks, applying a double-blinded design. Muscle mechanical...... effect of intervention. Maximal isometric contraction (b = 18.4 Nm, p = 0.039), RFD100 (b = 195.0 Nm/s, p = 0.017) and Dyn180 (b = 10.2 Nm, p = 0.019) increased during testosterone replacement therapy compared with placebo. No changes were observed in leg power or gait speed. Total lean body mass (b = 1...

  9. Muscles within muscles: a tensiomyographic and histochemical analysis of the normal human vastus medialis longus and vastus medialis obliquus muscles.

    Science.gov (United States)

    Travnik, Ludvik; Djordjevič, Srdjan; Rozman, Sergej; Hribernik, Marija; Dahmane, Raja

    2013-06-01

    The aim of this study was to show the connection between structure (anatomical and histochemical) and function (muscle contraction properties) of vastus medialis obliquus (VMO) and vastus medialis longus (VML). The non-invasive tensiomyography (TMG) method was used to determine the contractile properties (contraction time; T(c)) of VML and VMO muscle, as a reflection of the ratio between the slow and fast fibers in two groups of nine young men. VML and VMO significantly (P knee, and to the VMO, which maintains the stable position of the patella in the femoral groove. Our results obtained by TMG provided additional evidence that muscle fibers within the segments of VM muscle were not homogenous with regard to their contractile properties, thereby confirming the histochemical results. T(c) can be attributed to the higher percentage of slow-twitch fibers - type 1. The statistically shorter T(c) (P ≤ 0.001) of VMO (22.8 ± 4.0 ms) compared with VML (26.7 ± 4.0 ms) in our study is consistent with previously found differences in histochemical, morphological and electrophysiological data. In conclusion, the results of this study provide evidence that the VML and VMO muscles are not only anatomically and histochemically different muscles, but also functionally different biological structures.

  10. Low muscle glycogen and elevated plasma free fatty acid modify but do not prevent exercise-induced PDH activation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian; Gudmundsson, Mikkel; Birk, Jesper Bratz;

    2010-01-01

    Objective: Test the hypothesis that FFA and muscle glycogen modify exercise-induced regulation of PDH in human skeletal muscle through regulation of PDK4 expression. Research Design and Methods: On two occasions, healthy male subjects lowered (by exercise) muscle glycogen in one leg (LOW) relativ...

  11. Higher Daily Physical Activities Continue to Preserve Muscle Strength After Mid-Life, But Not Muscle Mass After Age of 75.

    Science.gov (United States)

    Hwang, An-Chun; Zhan, Yu-Rui; Lee, Wei-Ju; Peng, Li-Ning; Chen, Liang-Yu; Lin, Ming-Hsien; Liu, Li-Kuo; Chen, Liang-Kung

    2016-05-01

    The objective of this study is to explore the impact of aging and daily physical activities (PA) on muscle mass and muscle strength among community-dwelling people in Taiwan.The design is a cross-sectional study. Setting is a population-based community study.One thousand eight hundred thirty-nine community-dwelling people aged 50 years and older in Taiwan participated in the study.Measurements include demographic characteristics, Charlson Comorbidity Index (CCI) for multimorbidity, mini-nutritional assessment (MNA) for nutritional evaluation, functional autonomy measurement system (SMAF) for functional capacity, Chinese version mini mental state examination (MMSE), 5-item Taiwan Geriatric Depression Scale (TGDS-5), Chinese version of International Physical Activity Questionnaire (IPAQ), height-adjusted skeletal muscle index (SMI) by dual-energy X-ray absorptiometry, handgrip strength, timed 6-m walking test for usual gait speed. Laboratory measurements include testosterone, sex-hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), high-sensitivity C-reactive protein (hsCRP), 25-OH vitamin D, and insulin resistance.After adjusted for age, the lowest PA tertile was associated with multimorbidity, poorer functional capacity and nutritional status, more depressive symptoms, lower SMI and lower handgrip strength, and lower free androgen index (FAI) in men. The negative association between PA and low SMI was more significant among subjects aged younger than 65 and the association decreased with older age. For subjects aged younger than 65, moderate daily PA (Q2) group had lower risk of low SMI compared with Q1 participants (OR: 0.62, 95% CI = 0.39-0.98, P = 0.040). For muscle strength, higher daily PA was associated with lower risk of low handgrip strength after age of 65 and the effect was dose-dependent. The effect was attenuated by potential confounders during age 65 to 74, while after age 75, the

  12. Effects of muscle activation on shear between human soleus and gastrocnemius muscles.

    Science.gov (United States)

    Finni, T; Cronin, N J; Mayfield, D; Lichtwark, G A; Cresswell, A G

    2017-01-01

    Lateral connections between muscles provide pathways for myofascial force transmission. To elucidate whether these pathways have functional roles in vivo, we examined whether activation could alter the shear between the soleus (SOL) and lateral gastrocnemius (LG) muscles. We hypothesized that selective activation of LG would decrease the stretch-induced shear between LG and SOL. Eleven volunteers underwent a series of knee joint manipulations where plantar flexion force, LG, and SOL muscle fascicle lengths and relative displacement of aponeuroses between the muscles were obtained. Data during a passive full range of motion were recorded, followed by 20° knee extension stretches in both passive conditions and with selective electrical stimulation of LG. During active stretch, plantar flexion force was 22% greater (P muscles, at least at flexed knee joint angles, which may serve to facilitate myofascial force transmission. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    DEFF Research Database (Denmark)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng;

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees......, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy...

  14. HIV Infection Is Associated with Increased Fatty Infiltration of the Thigh Muscle with Aging Independent of Fat Distribution.

    Science.gov (United States)

    Natsag, Javzandulam; Erlandson, Kristine M; Sellmeyer, Deborah E; Haberlen, Sabina A; Margolick, Joseph; Jacobson, Lisa P; Palella, Frank J; Koletar, Susan L; Lake, Jordan E; Post, Wendy S; Brown, Todd T

    2017-01-01

    Lower muscle density on computed tomography (CT) provides a measure of fatty infiltration of muscle, an aspect of muscle quality that has been associated with metabolic abnormalities, weakness, decreased mobility, and increased fracture risk in older adults. We assessed the cross-sectional relationship between HIV serostatus, age, thigh muscle attenuation, and thigh muscle cross-sectional area (CSA). Mean CT-quantified Hounsfield units (HU) of the thigh muscle bundle and CSA were evaluated in 368 HIV-infected and 145 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study (MACS) Cardiovascular Substudy using multivariable linear regression. Models all were adjusted for HIV serostatus, age, race, and body mass index (BMI); each model was further adjusted for covariates that differed by HIV serostatus, including insulin resistance, hepatitis C, malignancy, smoking, alcohol use, and self-reported limitation in physical activity. HIV-infected men had greater thigh muscle CSA (pmuscle density (pMuscle density remained lower in HIV-infected men (p = 0.001) when abdominal visceral adiposity, and thigh subcutaneous adipose tissue area were substituted for BMI in a multivariable model. Muscle density decreased by 0.16 HU per year (pincreasing age among the HIV-infected men, but not in the HIV-uninfected men (HIV x age interaction -0.20 HU; p = 0.002). HIV-infected men had lower thigh muscle density compared to HIV-uninfected men, and a more pronounced decline with increasing age, indicative of greater fatty infiltration. These findings suggest that lower muscle quality among HIV-infected persons may be a risk factor for impairments in physical function with aging.

  15. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle

    Science.gov (United States)

    Vandenburgh, H.; Del Tatto, M.; Shansky, J.; Goldstein, L.; Russell, K.; Genes, N.; Chromiak, J.; Yamada, S.

    1998-01-01

    Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.

  16. Effect of postural angle on back muscle activities in aging female workers performing computer tasks

    OpenAIRE

    Kamil, Nabilla Sofia Mohd; Dawal, Siti Zawiah Md

    2015-01-01

    [Purpose] This study investigated the effects of postural angle on back muscle activity during a computer task in aging women. [Subjects] Seventeen women ≥50 years old participated. [Methods] The participants were instructed to perform computer-related tasks for 20 minutes on a workstation that simulated typical office working conditions. Back posture was measured from the measured trunk and pelvic angles. Electromyography activities were recorded simultaneously from the cervical erector spin...

  17. Functional Compartmentalization of the Human Superficial Masseter Muscle

    OpenAIRE

    Guzmán-Venegas, Rodrigo A.; Biotti Picand, Jorge L.; Francisco J Berral de la Rosa

    2015-01-01

    Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM) muscle's motor units using high-density surface e...

  18. Functional Echomyography of the human denervated muscle: first results

    Directory of Open Access Journals (Sweden)

    Riccardo Zanato

    2011-03-01

    Full Text Available In this study we followed with ultrasound three patients with permanent denervation to evaluate changes in morphology, thickness, contraction and vascularisation of muscles undergoing the home-based electrical stimulation program of the Rise2-Italy project. During a period of 1 year for the first subject, 6 months for the second subject and 3 months for the third subject we studied with ultrasound the denervated muscle comparing it (if possible to the contralateral normal muscle. We evaluated: 1. Changes in morphology and sonographic structure of the pathologic muscle; 2. Muscular thickness in response to the electrical stimulation therapy; 3. Short-term modifications in muscle perfusion and arterial flow patterns after stimulation; 4. Contraction-relaxation kinetic induced by volitional activity or electrical stimulation. Morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete muscular atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third than in the proximal and distal third of the denervated muscle, reaching in the last measurements of the first subject approximately the same thickness as the contralateral normal muscle. In all the measurements done within this study, arterial flow of the denervated muscle showed at rest a low-resistance pattern with Doppler Ultra Sound (US, and a pulsed pattern after electrical stimulation. The stimulation- induced pattern is similar to the trifasic high-resistance pattern of the normal muscle. Contraction- relaxation kinetic, measured by recording the muscular movements during electrical stimulation, showed an abnormal behaviour of the denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle (880 msec in the denervated muscle vs 240 msec in the contralateral normal one

  19. Multi-frequency bioimpedance in human muscle assessment

    DEFF Research Database (Denmark)

    Bartels, Else Marie; Sørensen, Emma Rudbæk; Harrison, Adrian Paul

    2015-01-01

    Bioimpedance analysis (BIA) is a well-known and tested method for body mass and muscular health assessment. Multi-frequency BIA (mfBIA) equipment now makes it possible to assess a particular muscle as a whole, as well as looking at a muscle at the fiber level. The aim of this study was to test......, contracted state, and cell transport/metabolic activity, which relate to muscle performance. Our findings indicate that mfBIA provides a noninvasive, easily measurable and very precise momentary assessment of skeletal muscles....

  20. Age-related changes in consolidation of perceptual and muscle-based learning of motor skills

    Directory of Open Access Journals (Sweden)

    Rebecca M. C. Spencer

    2013-11-01

    Full Text Available Improvements in motor sequence learning come about via goal-based learning of the sequence of visual stimuli and muscle-based learning of the sequence of movement responses. In young adults, consolidation of goal-based learning is observed after intervals of sleep but not following wake, whereas consolidation of muscle-based learning is greater following intervals with wake compared to sleep. While the benefit of sleep on motor sequence learning has been shown to decline with age, how sleep contributes to consolidation of goal-based versus muscle-based learning in older adults has not been disentangled. We trained young (n=62 and older (n=50 adults on a motor sequence learning task and re-tested learning following 12 hr intervals containing overnight sleep or daytime wake. To probe consolidation of goal-based learning of the sequence, half of the participants were re-tested in a configuration in which the stimulus sequence was the same but, due to a shift in stimulus-response mapping, the movement response sequence differed. To probe consolidation of muscle-based learning, the remaining participants were tested in a configuration in which the stimulus sequence was novel, but now the sequence of movements used for responding was unchanged. In young adults, there was a significant condition (goal-based v. muscle-based learning by interval (sleep v. wake interaction, F(1,58=6.58, p=.013: Goal-based learning tended to be greater following sleep compared to wake, t(29=1.47, p=.072. Conversely, muscle-based learning was greater following wake than sleep, t(29=2.11, p=.021. Unlike young adults, this interaction was not significant in older adults, F(1,46=.04, p=.84, nor was there a main effect of interval, F(1,46=1.14, p=.29. Thus, older adults do not preferentially consolidate sequence learning over wake or sleep.