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The International Journal of... Oct 2013Loss of skeletal muscle mass occurs frequently in clinical settings in response to joint immobilization and bed rest, and is induced by a combination of unloading and... (Review)
Review
Loss of skeletal muscle mass occurs frequently in clinical settings in response to joint immobilization and bed rest, and is induced by a combination of unloading and inactivity. Disuse-induced atrophy will likely affect every person in his or her lifetime, and can be debilitating especially in the elderly. Currently there are no good therapies to treat disuse-induced muscle atrophy, in part, due to a lack of understanding of the cellular and molecular mechanisms responsible for the induction and maintenance of muscle atrophy. Our current understanding of disuse atrophy comes from the investigation of a variety of models (joint immobilization, hindlimb unloading, bed rest, spinal cord injury) in both animals and humans. Under conditions of unloading, it is widely accepted that there is a decrease in protein synthesis, however, the role of protein degradation, especially in humans, is debated. This review will examine the current understanding of the molecular and cellular mechanisms regulating muscle loss under disuse conditions, discussing the similarities and areas of dispute between the animal and human literature. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
Topics: Animals; Humans; Muscle Proteins; Muscular Atrophy; Protein Biosynthesis
PubMed: 23800384
DOI: 10.1016/j.biocel.2013.06.011 -
Journal of Cachexia, Sarcopenia and... Aug 2018In recent years, electrical myostimulation (EMS) is becoming more and more popular to increase muscle function and muscle weight. Especially it is applied in healthy...
In recent years, electrical myostimulation (EMS) is becoming more and more popular to increase muscle function and muscle weight. Especially it is applied in healthy individual after injury to rebuild muscle mass and in severely atrophic patients who are not able or willing to perform conventional exercise training programs. Studies in experimental models as well as in human subjects confirmed that EMS can increase muscle mass by around 1% and improve muscle function by around 10-15% after 5-6 weeks of treatment. Despite a severe increase in circulating creatine kinase during the first session, EMS can be regarded as a safe therapeutic intervention. At the molecular level, EMS improves the anabolic/catabolic balance and stimulates the regenerative capacity of satellite cells. EMS intensity should be as high as individually tolerated, and a minimum of three sessions per week [large pulses (between 300-450 μs), high frequency (50-100 Hz in young and around 30 Hz in older individuals)] for at least 5-6 weeks should be performed. EMS improved functional performances more effectively than voluntary training and counteracted fast type muscle fibre atrophy, typically associated with sarcopenia. The effect of superimposing EMS on conventional exercise training to achieve more muscle mass and better function is still discussed controversially. Nevertheless, EMS should not be regarded as a replacement of exercise training per se, since the beneficial effect of exercise training is not just relying on building muscle mass but it also exerts positive effects on endothelial, myocardial, and cognitive function.
Topics: Animals; Clinical Studies as Topic; Disease Models, Animal; Electric Stimulation Therapy; Humans; Muscular Atrophy; Treatment Outcome
PubMed: 30028092
DOI: 10.1002/jcsm.12332 -
The EMBO Journal Jul 2017Adipose tissue represents a critical component in healthy energy homeostasis. It fulfills important roles in whole-body lipid handling, serves as the body's major energy... (Review)
Review
Adipose tissue represents a critical component in healthy energy homeostasis. It fulfills important roles in whole-body lipid handling, serves as the body's major energy storage compartment and insulation barrier, and secretes numerous endocrine mediators such as adipokines or lipokines. As a consequence, dysfunction of these processes in adipose tissue compartments is tightly linked to severe metabolic disorders, including obesity, metabolic syndrome, lipodystrophy, and cachexia. While numerous studies have addressed causes and consequences of obesity-related adipose tissue hypertrophy and hyperplasia for health, critical pathways and mechanisms in (involuntary) adipose tissue loss as well as its systemic metabolic consequences are far less understood. In this review, we discuss the current understanding of conditions of adipose tissue wasting and review microenvironmental determinants of adipocyte (dys)function in related pathophysiologies.
Topics: Adipokines; Adipose Tissue; Animals; Atrophy; Energy Metabolism; Homeostasis; Humans; Lipid Metabolism; Obesity
PubMed: 28623240
DOI: 10.15252/embj.201696206 -
Biomedicine & Pharmacotherapy =... Sep 2021Atrophy is defined as a reduction in cell, organ, or tissue size after reaching their normal mature sizes because of loss of organelles, cytoplasmic compartments, and... (Review)
Review
Atrophy is defined as a reduction in cell, organ, or tissue size after reaching their normal mature sizes because of loss of organelles, cytoplasmic compartments, and proteins. This process is also involved in the pathogenesis of human disorders. Inadequate nourishment, poor circulation, inadequate hormonal support, defects in nerve supply of the tissue, disproportionate induction of apoptosis in the tissue, and absence of exercise are some underlying causes of atrophy. Recently, several non-coding RNAs (ncRNAs) have been identified that regulate atrophy, thus participating in the pathobiology of related disorders such as neurodegenerative/ neuromuscular diseases, age-related muscle atrophy, and cardiac tissue atrophy. In the current review, we have focused on two classes of ncRNAs namely long ncRNAs (lncRNAs) and microRNAs (miRNAs) to unravel their participation in atrophy-associated disorders.
Topics: Animals; Atrophy; Humans; RNA, Long Noncoding
PubMed: 34146849
DOI: 10.1016/j.biopha.2021.111820 -
Translational Neurodegeneration Dec 2023TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal...
BACKGROUND
TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum.
METHODS
We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS-FTD patients with likely TDP-43. A Subtype and Stage Inference (SuStaIn) model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns, and we related subtypes and stages to clinical, genetic, and neuropathological features of disease.
RESULTS
SuStaIn identified three novel subtypes: two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions, and a normal-appearing group without obvious brain atrophy. The limbic-predominant subtype tended to present with more impaired cognition, higher frequencies of pathogenic variants in TBK1 and TARDBP genes, and a higher proportion of TDP-43 types B, E and C. In contrast, the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A. The normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients, higher cognitive capacity, higher proportion of lower motor neuron onset, milder motor symptoms, and lower frequencies of genetic pathogenic variants. The overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration, higher King's stage, and cognitive decline. Additionally, SuStaIn stages differed across clinical phenotypes, genotypes and types of TDP-43 pathology.
CONCLUSIONS
Our findings suggest distinct neurodegenerative subtypes of disease along the ALS-FTD spectrum that can be identified in vivo, each with distinct brain atrophy, clinical, genetic and pathological patterns.
Topics: Humans; Amyotrophic Lateral Sclerosis; Frontotemporal Dementia; Neurodegenerative Diseases; Brain; DNA-Binding Proteins; Atrophy
PubMed: 38062485
DOI: 10.1186/s40035-023-00389-3 -
Journal of Cachexia, Sarcopenia and... Dec 2017Precision (P4) medicine represents a new medical paradigm that focuses on Personalized, Predictive, Preventive and Participatory approaches. The P4 paradigm is...
Precision (P4) medicine represents a new medical paradigm that focuses on Personalized, Predictive, Preventive and Participatory approaches. The P4 paradigm is particularly appropriate for moving the care of persons with myopenia forward. Muscular dystrophies are clearly a set of genetically different diseases where genomics are the basis of diagnosis, and genetic modulation via DNA, oligonucleotides and clustered regularly interspaced short palendronic repeats hold great potential for a cure. The utility of personalized genomics for sarcopenia coupled with utilizing a predictive approach for the diagnosis with early preventive strategies is a key to improving sarcopenic outcomes. The importance of understanding different levels of patient enthusiasm and different responses to exercise should guide the participatory phase of sarcopenic treatment. In the case of cachexia, understanding the effects of the different therapies now available through the P4 approach on muscle wasting is a key to management strategies.
Topics: Animals; Cachexia; Humans; Muscular Atrophy; Precision Medicine; Sarcopenia
PubMed: 28944582
DOI: 10.1002/jcsm.12231 -
American Journal of Physiology.... Jul 2022Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving... (Review)
Review
Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving health and performance across the lifespan. Based largely on cellular and animal models, there is some evidence that various forms of heat stress with or without resistance exercise may enhance skeletal muscle growth or reduce its loss. It is not clear whether these stimuli are similarly effective in humans or meaningful compared with exercise alone across various heating methodologies. Furthermore, the magnitude by which heat stress may influence whole body thermoregulatory responses and the connection to skeletal muscle adaptation remains ambiguous. Finally, the underlying mechanisms, which may include interaction between relevant heat shock proteins and intracellular hypertrophy and atrophy related factors, remain unclear. In this narrative review, we examine the relevant literature regarding heat stress alone or in combination with resistance exercise emphasizing skeletal muscle hypertrophy and atrophy across cellular and animal models, as well as human investigations. In addition, we present working mechanistic theories for heat shock protein-mediated signaling effects regarding hypertrophy and atrophy-related signaling processes. Importantly, continued research is necessary to determine the practical effects and mechanisms of heat stress with and without resistance exercise on skeletal muscle function via growth and maintenance.
Topics: Animals; Atrophy; Exercise; Heat-Shock Proteins; Heat-Shock Response; Hypertrophy; Muscle, Skeletal; Muscular Atrophy
PubMed: 35536704
DOI: 10.1152/ajpregu.00048.2022 -
The International Journal of... Oct 2013The ubiquitin proteasome system plays a critical role in skeletal muscle atrophy. A large body of research has revealed that many ubiquitin ligases are induced and play... (Review)
Review
The ubiquitin proteasome system plays a critical role in skeletal muscle atrophy. A large body of research has revealed that many ubiquitin ligases are induced and play an important role in mediating the wasting. However, relatively little is known about the roles of deubiquitinases in this process. Although it might be expected that deubiquitinases would be downregulated in atrophying muscles to promote ubiquitination and degradation of muscle proteins, this has not to date been demonstrated. Instead several deubiquitinases are induced in atrophying muscle, in particular USP19 and USP14. USP19, USP2 and A20 are also implicated in myogenesis. USP19 has been most studied to date. Its expression is increased in both systemic and disuse forms of atrophy and can be regulated through a p38 MAP kinase signaling pathway. In cultured muscle cells, it decreases the expression of myofibrillar proteins by apparently suppressing their transcription indicating that the ubiquitin proteasome system may be activated in skeletal muscle to not only increase protein degradation, but also to suppress protein synthesis. Deubiquitinases may be upregulated in atrophy in order to maintain the pool of free ubiquitin required for the increased overall conjugation and degradation of muscle proteins as well as to regulate the stability and function of proteins that are essential in mediating the wasting. Although deubiquitinases are not well studied, these early insights indicate that some of these enzymes play important roles and may be therapeutic targets for the prevention and treatment of muscle atrophy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
Topics: Animals; Humans; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Proteasome Endopeptidase Complex; Ubiquitin-Specific Proteases
PubMed: 23680672
DOI: 10.1016/j.biocel.2013.05.002 -
The British Journal of General Practice... Dec 2021
Topics: Atrophy; Humans; Urogenital System
PubMed: 34824066
DOI: 10.3399/bjgp21X717725 -
Tidsskrift For Den Norske Laegeforening... Jun 2015Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal... (Review)
Review
BACKGROUND
Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal and temporal cortices. It presents early, in the 50s or 60s, with nonspecific visual disturbances that are often misinterpreted as ophthalmological, which can delay the diagnosis. The purpose of this article is to present current knowledge about symptoms, diagnostics and treatment of this condition.
METHOD
The review is based on a selection of relevant articles in PubMed and on the authors' own experience with the patient group.
RESULTS
Posterior cortical atrophy causes gradually increasing impairment in reading, distance judgement, and the ability to perceive complex images. Examination of higher visual functions, neuropsychological testing, and neuroimaging contribute to diagnosis. In the early stages, patients do not have problems with memory or insight, but cognitive impairment and dementia can develop. It is unclear whether the condition is a variant of Alzheimer's disease, or whether it is a separate disease entity. There is no established treatment, but practical measures such as the aid of social care workers, telephones with large keypads, computers with voice recognition software and audiobooks can be useful.
INTERPRETATION
Currently available treatment has very limited effect on the disease itself. Nevertheless it is important to identify and diagnose the condition in its early stages in order to be able to offer patients practical assistance in their daily lives.
Topics: Aged; Atrophy; Cerebral Cortex; Disease Progression; Humans; Middle Aged; Neurodegenerative Diseases; Positron-Emission Tomography; Vision Disorders
PubMed: 26037756
DOI: 10.4045/tidsskr.14.1127