The Experts below are selected from a list of 498 Experts worldwide ranked by ideXlab platform
Adam P Sharples - One of the best experts on this subject based on the ideXlab platform.
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Exercise and DNA methylation in skeletal Muscle
Sports Exercise and Nutritional Genomics, 2019Co-Authors: Adam P Sharples, Robert A SeaborneAbstract:Abstract Molecular exercise physiology is the study of the underlying molecular regulatory mechanisms that underpin physiological adaptation to exercise. The molecular mechanisms studied include; inherited DNA traits and mutations (genetics), extracellular and intracellular signaling, gene expression, and protein translation in the major tissues and organs that are required for exercise, particularly skeletal Muscle. Within the molecular exercise physiology field, epigenetics is an emerging and exciting area that is beginning to enhance our understanding of how environmental exposures to exercise can affect the regulation of our inherited DNA, affecting the extent to which genes are turned on and off (gene/mRNA expression). DNA methylation is one of the major epigenetic modifications that can regulate gene expression following environmental encounters with exercise without changes to the genetic code. Therefore, this chapter provides an overview of our current understanding for the role of DNA methylation in response to acute aerobic and resistance exercise, as well as its function in regulating gene expression following chronic exercise. Finally, we review the emerging and exciting area of epigenetic Muscle Memory and the role of DNA methylation in this phenomenon, and provide important directions for future research in this area.
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does skeletal Muscle have an epi Memory the role of epigenetics in nutritional programming metabolic disease aging and exercise
Aging Cell, 2016Co-Authors: Adam P Sharples, Claire E Stewart, Robert A SeaborneAbstract:Summary 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.
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skeletal Muscle cells possess a Memory of acute early life tnf α exposure role of epigenetic adaptation
Biogerontology, 2016Co-Authors: Adam P Sharples, Ioanna Polydorou, David C Hughes, Daniel J Owens, T M Hughes, Claire E StewartAbstract:Sufficient quantity and quality of skeletal Muscle is required to maintain lifespan and healthspan into older age. The concept of skeletal Muscle programming/Memory has been suggested to contribute to accelerated Muscle decline in the elderly in association with early life stress such as fetal malnutrition. Further, Muscle cells in vitro appear to remember the in vivo environments from which they are derived (e.g. cancer, obesity, type II diabetes, physical inactivity and nutrient restriction). Tumour-necrosis factor alpha (TNF-α) is a pleiotropic cytokine that is chronically elevated in sarcopenia and cancer cachexia. Higher TNF-α levels are strongly correlated with Muscle loss, reduced strength and therefore morbidity and earlier mortality. We have extensively shown that TNF-α impairs regenerative capacity in mouse and human Muscle derived stem cells [Meadows et al. (J Cell Physiol 183(3):330-337, 2000); Foulstone et al. (J Cell Physiol 189(2):207-215, 2001); Foulstone et al. (Exp Cell Res 294(1):223-235, 2004); Stewart et al. (J Cell Physiol 198(2):237-247, 2004); Al-Shanti et al. (Growth factors (Chur, Switzerland) 26(2):61-73, 2008); Saini et al. (Growth factors (Chur, Switzerland) 26(5):239-253, 2008); Sharples et al. (J Cell Physiol 225(1):240-250, 2010)]. We have also recently established an epigenetically mediated mechanism (SIRT1-histone deacetylase) regulating survival of myoblasts in the presence of TNF-α [Saini et al. (Exp Physiol 97(3):400-418, 2012)]. We therefore wished to extend this work in relation to Muscle Memory of catabolic stimuli and the potential underlying epigenetic modulation of Muscle loss. To enable this aim; C2C12 myoblasts were cultured in the absence or presence of early TNF-α (early proliferative lifespan) followed by 30 population doublings in the absence of TNF-α, prior to the induction of differentiation in low serum media (LSM) in the absence or presence of late TNF-α (late proliferative lifespan). The cells that received an early plus late lifespan dose of TNF-α exhibited reduced morphological (myotube number) and biochemical (creatine kinase activity) differentiation vs. control cells that underwent the same number of proliferative divisions but only a later life encounter with TNF-α. This suggested that Muscle cells had a morphological Memory of the acute early lifespan TNF-α encounter. Importantly, methylation of myoD CpG islands were increased in the early TNF-α cells, 30 population doublings later, suggesting that even after an acute encounter with TNF-α, the cells have the capability of retaining elevated methylation for at least 30 cellular divisions. Despite these fascinating findings, there were no further increases in myoD methylation or changes in its gene expression when these cells were exposed to a later TNF-α dose suggesting that this was not directly responsible for the decline in differentiation observed. In conclusion, data suggest that elevated myoD methylation is retained throughout Muscle cells proliferative lifespan as result of early life TNF-α treatment and has implications for the epigenetic control of Muscle loss.
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Does skeletal Muscle have an ‘epi’-Memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise
Aging Cell, 2016Co-Authors: Adam P Sharples, Claire E Stewart, Robert A SeaborneAbstract:Summary 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.
Joonyoung Park - One of the best experts on this subject based on the ideXlab platform.
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a cellular mechanism of Muscle Memory facilitates mitochondrial remodelling following resistance training
The Journal of Physiology, 2018Co-Authors: Junchul Shin, Sudarsan Rajan, Jingwei Wu, Xiongwen Chen, Michael D Brown, Joonyoung ParkAbstract:Key points Referring to the Muscle Memory theory, previously trained Muscles acquire strength and volume much faster than naive Muscles. Using extreme experimental models such as synergist ablation or steroid administration, previous studies have demonstrated that the number of nuclei increases when a Muscle becomes enlarged, which serves as a cellular Muscle Memory mechanism for the Muscle. In the present study, we found that, when rats were subjected to physiologically relevant resistance training, the number of myonuclei increased and was retained during a long-term detraining period. The acquired myonuclei were related to a greater degree of Muscle hypertrophic and mitochondrial biogenesis processes following subsequent hypertrophic conditions. Our data suggest a cellular mechanism supporting the notion that exposing young Muscles to resistance training would help to restore age-related Muscle loss coupled with mitochondrial dysfunction in later life. Abstract Muscle hypertrophy induced by resistance training is accompanied by an increase in the number of myonuclei. The acquired myonuclei are viewed as a cellular component of Muscle Memory by which Muscle enlargement is promoted during a re-training period. In the present study, we investigated the effect of exercise preconditioning on mitochondrial remodelling induced by resistance training. Sprague-Dawley rats were divided into four groups: untrained control, training, pre-training or re-training. The training groups were subjected to weight loaded-ladder climbing exercise training. Myonuclear numbers were significantly greater (up to 20%) in all trained Muscles compared to untrained controls. Muscle mass was significantly higher in the re-training group compared to the training group (∼2-fold increase). Mitochondrial content, mitochondrial biogenesis gene expression levels and mitochondrial DNA copy numbers were significantly higher in re-trained Muscles compared to the others. Oxidative myofibres (type I) were significantly increased only in the re-trained Muscles. Furthermore, in vitro studies using insulin-like growth factor-1-treated L6 rat myotubes demonstrated that myotubes with a higher myonuclear number confer greater expression levels of both mitochondrial and nuclear genes encoding for constitutive and regulatory mitochondrial proteins, which also showed a greater mitochondrial respiratory function. These data suggest that myonuclei acquired from previous training facilitate mitochondrial biogenesis in response to subsequent retraining by (at least in part) enhancing cross-talk between mitochondria and myonuclei in the pre-conditioned myofibres.
Robert A Seaborne - One of the best experts on this subject based on the ideXlab platform.
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Exercise and DNA methylation in skeletal Muscle
Sports Exercise and Nutritional Genomics, 2019Co-Authors: Adam P Sharples, Robert A SeaborneAbstract:Abstract Molecular exercise physiology is the study of the underlying molecular regulatory mechanisms that underpin physiological adaptation to exercise. The molecular mechanisms studied include; inherited DNA traits and mutations (genetics), extracellular and intracellular signaling, gene expression, and protein translation in the major tissues and organs that are required for exercise, particularly skeletal Muscle. Within the molecular exercise physiology field, epigenetics is an emerging and exciting area that is beginning to enhance our understanding of how environmental exposures to exercise can affect the regulation of our inherited DNA, affecting the extent to which genes are turned on and off (gene/mRNA expression). DNA methylation is one of the major epigenetic modifications that can regulate gene expression following environmental encounters with exercise without changes to the genetic code. Therefore, this chapter provides an overview of our current understanding for the role of DNA methylation in response to acute aerobic and resistance exercise, as well as its function in regulating gene expression following chronic exercise. Finally, we review the emerging and exciting area of epigenetic Muscle Memory and the role of DNA methylation in this phenomenon, and provide important directions for future research in this area.
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does skeletal Muscle have an epi Memory the role of epigenetics in nutritional programming metabolic disease aging and exercise
Aging Cell, 2016Co-Authors: Adam P Sharples, Claire E Stewart, Robert A SeaborneAbstract:Summary 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.
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Does skeletal Muscle have an ‘epi’-Memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise
Aging Cell, 2016Co-Authors: Adam P Sharples, Claire E Stewart, Robert A SeaborneAbstract:Summary 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.
Claire E Stewart - One of the best experts on this subject based on the ideXlab platform.
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does skeletal Muscle have an epi Memory the role of epigenetics in nutritional programming metabolic disease aging and exercise
Aging Cell, 2016Co-Authors: Adam P Sharples, Claire E Stewart, Robert A SeaborneAbstract:Summary 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.
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skeletal Muscle cells possess a Memory of acute early life tnf α exposure role of epigenetic adaptation
Biogerontology, 2016Co-Authors: Adam P Sharples, Ioanna Polydorou, David C Hughes, Daniel J Owens, T M Hughes, Claire E StewartAbstract:Sufficient quantity and quality of skeletal Muscle is required to maintain lifespan and healthspan into older age. The concept of skeletal Muscle programming/Memory has been suggested to contribute to accelerated Muscle decline in the elderly in association with early life stress such as fetal malnutrition. Further, Muscle cells in vitro appear to remember the in vivo environments from which they are derived (e.g. cancer, obesity, type II diabetes, physical inactivity and nutrient restriction). Tumour-necrosis factor alpha (TNF-α) is a pleiotropic cytokine that is chronically elevated in sarcopenia and cancer cachexia. Higher TNF-α levels are strongly correlated with Muscle loss, reduced strength and therefore morbidity and earlier mortality. We have extensively shown that TNF-α impairs regenerative capacity in mouse and human Muscle derived stem cells [Meadows et al. (J Cell Physiol 183(3):330-337, 2000); Foulstone et al. (J Cell Physiol 189(2):207-215, 2001); Foulstone et al. (Exp Cell Res 294(1):223-235, 2004); Stewart et al. (J Cell Physiol 198(2):237-247, 2004); Al-Shanti et al. (Growth factors (Chur, Switzerland) 26(2):61-73, 2008); Saini et al. (Growth factors (Chur, Switzerland) 26(5):239-253, 2008); Sharples et al. (J Cell Physiol 225(1):240-250, 2010)]. We have also recently established an epigenetically mediated mechanism (SIRT1-histone deacetylase) regulating survival of myoblasts in the presence of TNF-α [Saini et al. (Exp Physiol 97(3):400-418, 2012)]. We therefore wished to extend this work in relation to Muscle Memory of catabolic stimuli and the potential underlying epigenetic modulation of Muscle loss. To enable this aim; C2C12 myoblasts were cultured in the absence or presence of early TNF-α (early proliferative lifespan) followed by 30 population doublings in the absence of TNF-α, prior to the induction of differentiation in low serum media (LSM) in the absence or presence of late TNF-α (late proliferative lifespan). The cells that received an early plus late lifespan dose of TNF-α exhibited reduced morphological (myotube number) and biochemical (creatine kinase activity) differentiation vs. control cells that underwent the same number of proliferative divisions but only a later life encounter with TNF-α. This suggested that Muscle cells had a morphological Memory of the acute early lifespan TNF-α encounter. Importantly, methylation of myoD CpG islands were increased in the early TNF-α cells, 30 population doublings later, suggesting that even after an acute encounter with TNF-α, the cells have the capability of retaining elevated methylation for at least 30 cellular divisions. Despite these fascinating findings, there were no further increases in myoD methylation or changes in its gene expression when these cells were exposed to a later TNF-α dose suggesting that this was not directly responsible for the decline in differentiation observed. In conclusion, data suggest that elevated myoD methylation is retained throughout Muscle cells proliferative lifespan as result of early life TNF-α treatment and has implications for the epigenetic control of Muscle loss.
-
Does skeletal Muscle have an ‘epi’-Memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise
Aging Cell, 2016Co-Authors: Adam P Sharples, Claire E Stewart, Robert A SeaborneAbstract:Summary 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.
Carl Johan Sundberg - One of the best experts on this subject based on the ideXlab platform.
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the impact of endurance training on human skeletal Muscle Memory global isoform expression and novel transcripts
PLOS Genetics, 2016Co-Authors: Malene E Lindholm, Stefania Giacomello, Beata Werne Solnestam, Helene Fischer, Mikael Huss, Sanela Kjellqvist, Carl Johan SundbergAbstract:Regularly performed endurance training has many beneficial effects on health and skeletal Muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal Muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional Memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal Muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal Muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein-coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal Muscle Memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity.
