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Molecular Oncology Feb 2024Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of... (Review)
Review
Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of cancer patients succumb directly to Ccx, yet therapies that effectively address this perturbed metabolic state are rare. In recent decades, several characteristics of Ccx have been established in mice and humans, of which we here highlight adipose tissue dysfunction, muscle wasting and systemic inflammation, as they are directly linked to biomarker discovery. To counteract cachexia pathogenesis as early as possible and mitigate its detrimental impact on anti-cancer treatments, identification and validation of clinically endorsed biomarkers assume paramount importance. Ageing was recently shown to affect both the validity of Ccx biomarkers and Ccx development, but the underlying mechanisms are still unknown. Thus, unravelling the intricate interplay between ageing and Ccx can help to counteract Ccx pathogenesis and tailor diagnostic and treatment strategies to individual needs.
PubMed: 38414161
DOI: 10.1002/1878-0261.13590 -
Biology Nov 2023Exercise is widely recognized for its positive impact on human health and well-being. The process of utilizing substrates in skeletal muscle during exercise is intricate... (Review)
Review
Exercise is widely recognized for its positive impact on human health and well-being. The process of utilizing substrates in skeletal muscle during exercise is intricate and governed by complex mechanisms. Carbohydrates and lipids serve as the primary fuel sources for skeletal muscle during exercise. It is now understood that fuel selection during exercise is not solely determined by physical activity itself but is also influenced by the overall metabolic state of the body. The balance between lipid and carbohydrate utilization significantly affects exercise capacity, including endurance, fatigue, and overall performance. Therefore, comprehensively understanding the regulation of substrate utilization during exercise is of utmost importance. The aim of this review is to provide an extensive overview of the current knowledge regarding the pathways involved in the regulation of substrate utilization during exercise. By synthesizing existing research, we can gain a holistic perspective on the intricate relationship between exercise, metabolism, and fuel selection. This advanced understanding has the potential to drive advancements in the field of exercise science and contribute to the development of personalized exercise strategies for individuals looking to optimize their performance and overall health.
PubMed: 37998049
DOI: 10.3390/biology12111450 -
Dysphagia Aug 2023Muscle fatigue is the diminution of force required for a particular action over time. Fatigue may be particularly pronounced in aging muscles, including those used for... (Review)
Review
Muscle fatigue is the diminution of force required for a particular action over time. Fatigue may be particularly pronounced in aging muscles, including those used for swallowing actions. Because risk for swallowing impairment (dysphagia) increases with aging, the contribution of muscle fatigue to age-related dysphagia is an emerging area of interest. The use of animal models, such as mice and rats (murine models) allows experimental paradigms for studying the relationship between muscle fatigue and swallowing function with a high degree of biological precision that is not possible in human studies. The goal of this article is to review basic experimental approaches to the study of murine tongue muscle fatigue related to dysphagia. Traditionally, murine muscle fatigue has been studied in limb muscles through direct muscle stimulation and behavioral exercise paradigms. As such, physiological and bioenergetic markers of muscle fatigue that have been validated in limb muscles may be applicable in studies of cranial muscle fatigue with appropriate modifications to account for differences in muscle architecture, innervation ratio, and skeletal support. Murine exercise paradigms may be used to elicit acute fatigue in tongue muscles, thereby enabling study of putative muscular adaptations. Using these approaches, hypotheses can be developed and tested in mice and rats to allow for future focused studies in human subjects geared toward developing and optimizing treatments for age-related dysphagia.
Topics: Humans; Rats; Mice; Animals; Muscle Fatigue; Deglutition Disorders; Muscle, Skeletal; Tongue; Deglutition
PubMed: 36401630
DOI: 10.1007/s00455-022-10537-y -
Journal of Cachexia, Sarcopenia and... Oct 2023There is increasing evidence that neurodegenerative disorders including the Parkinsonian syndromes are associated with impaired skeletal muscle health, manifesting as... (Review)
Review
There is increasing evidence that neurodegenerative disorders including the Parkinsonian syndromes are associated with impaired skeletal muscle health, manifesting as wasting and weakness. Many of the movement problems, lack of muscle strength and reduction in quality of life that are characteristic of these syndromes can be attributed to impairments in skeletal muscle health, but this concept has been grossly understudied and represents an important area of unmet clinical need. This review describes the changes in skeletal muscle health in idiopathic Parkinson's disease and in two atypical Parkinsonian syndromes, the most aggressive synucleinopathy multiple system atrophy, and the tauopathy progressive supranuclear palsy. The pathogenesis of the skeletal muscle changes is described, including the contribution of impairments to the central and peripheral nervous system and intrinsic alterations. Pharmacological interventions targeting the underlying molecular mechanisms with therapeutic potential to improve skeletal muscle health in affected patients are also discussed. Although little is known about the mechanisms underlying these conditions, current evidence implicates multiple pathways and processes, highlighting the likely need for combination therapies to protect muscle health and emphasizing the merit of personalized interventions for patients with different physical capacities at different stages of their disease. As muscle fatigue is often experienced by patients prior to diagnosis, the identification and measurement of this symptom and related biomarkers to identify early signs of disease require careful interrogation, especially for multiple system atrophy and progressive supranuclear palsy where diagnosis is often made several years after onset of symptoms and only confirmed post-mortem. We propose a multidisciplinary approach for early diagnosis and implementation of personalized interventions to preserve muscle health and improve quality of life for patients with typical and atypical Parkinsonian syndromes.
PubMed: 37574254
DOI: 10.1002/jcsm.13312 -
Clinical Neurophysiology Practice 2024Though a common symptom, fatigue is difficult to define and investigate, occurs in a wide variety of neurological and systemic disorders, with differing pathological... (Review)
Review
Though a common symptom, fatigue is difficult to define and investigate, occurs in a wide variety of neurological and systemic disorders, with differing pathological causes. It is also often accompanied by a psychological component. As a symptom of long-term COVID-19 it has gained more attention. In this review, we begin by differentiating fatigue, a perception, from fatigability, quantifiable through biomarkers. Central and peripheral nervous system and muscle disorders associated with these are summarised. We provide a comprehensive and objective framework to help identify potential causes of fatigue and fatigability in a given disease condition. It also considers the effectiveness of neurophysiological tests as objective biomarkers for its assessment. Among these, twitch interpolation, motor cortex stimulation, electroencephalography and magnetencephalography, and readiness potentials will be described for the assessment of central fatigability, and surface and needle electromyography (EMG), single fibre EMG and nerve conduction studies for the assessment of peripheral fatigability. The purpose of this review is to guide clinicians in how to approach fatigue, and fatigability, and to suggest that neurophysiological tests may allow an understanding of their origin and interactions. In this way, their differing types and origins, and hence their possible differing treatments, may also be defined more clearly.
PubMed: 38274859
DOI: 10.1016/j.cnp.2023.12.004 -
PloS One 2023Post-Covid-19 syndrome is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The most...
PURPOSE
Post-Covid-19 syndrome is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The most common symptoms include reduced exercise tolerance and capacity, fatigue, neurocognitive problems, muscle pain and dyspnea. The aim of our work was to investigate exercise capacity and markers of subjective wellbeing and their independent relation to post-COVID-19 syndrome.
PATIENTS AND METHODS
We examined a total of 69 patients with post-COVID-19 syndrome (23 male/46 female; age 46±12 years; BMI 28.9±6.6 kg/m2) with fatigue and a score ≥22 in the Fatigue Assessment Scale (FAS). We assessed exercise capacity on a cycle ergometer, a 6-minute walk test, the extent of fatigue (FAS), markers of health-related quality of life (SF-36 questionnaire) and mental health (HADS).
RESULTS
On average the Fatigue Assessment Scale was 35.0±7.4 points. Compared with normative values the VO2max/kg was reduced by 8.6±5.8 ml/min/kg (27.7%), the 6MWT by 71±96 m (11.9%), the health-related quality of life physical component score by 15.0±9.0 points (29.9%) and the mental component score by 10.6±12.8 points (20.6%). Subdivided into mild fatigue (FAS score 22-34) and severe fatigue (FAS score ≥35), patients with severe fatigue showed a significant reduction of the 6-minute walk test by 64±165 m (p<0.01) and the health-related quality of life physical component score by 5.8±17.2 points (p = 0.01). In multiple regression analysis age (β = -0.24, p = 0.02), sex (β = 0.22, p = 0.03), mental (β = -0.51, p<0.01) and physical (β = -0.44, p<0.01) health-related quality of life and by trend the 6-minute walk test (β = -0.22, p = 0.07) were associated with the FAS.
CONCLUSION
Patients with post-COVID-19 syndrome show reduced maximal and submaximal physical performance as well as limitations in quality of life, particularly pronounced in the physical components. These results are essentially influenced by the severity of fatigue and implicating the need for targeted treatments.
Topics: Humans; Male; Female; Adult; Middle Aged; Quality of Life; Post-Acute COVID-19 Syndrome; COVID-19; SARS-CoV-2; Fatigue
PubMed: 37870989
DOI: 10.1371/journal.pone.0292928 -
Foods (Basel, Switzerland) Aug 2023Due to today's fast-paced lifestyle, most people are in a state of sub-health and face "unexplained fatigue", which can seriously affect their health, work efficiency,... (Review)
Review
Due to today's fast-paced lifestyle, most people are in a state of sub-health and face "unexplained fatigue", which can seriously affect their health, work efficiency, and quality of life. Fatigue is also a common symptom of several serious diseases such as Parkinson's, Alzheimer's, cancer, etc. However, the contributing mechanisms are not clear, and there are currently no official recommendations for the treatment of fatigue. Some dietary polysaccharides are often used as health care supplements; these have been reported to have specific anti-fatigue effects, with minor side effects and rich pharmacological activities. Dietary polysaccharides can be activated during food processing or during gastrointestinal transit, exerting unique effects. This review aims to comprehensively summarize and evaluate the latest advances in the biological processes of exercise-induced fatigue, to understand dietary polysaccharides and their possible molecular mechanisms in alleviating exercise-induced fatigue, and to systematically elaborate the roles of gut microbiota and the gut-muscle axis in this process. From the perspective of the gut-muscle axis, investigating the relationship between polysaccharides and fatigue will enhance our understanding of fatigue and may lead to a significant breakthrough regarding the molecular mechanism of fatigue. This paper will provide new perspectives for further research into the use of polysaccharides in food science and food nutrition, which could help develop potential anti-fatigue agents and open up novel therapies for sub-health conditions.
PubMed: 37628082
DOI: 10.3390/foods12163083 -
Journal of the International Society of... Dec 2023Post-exercise muscle soreness and fatigue can negatively affect exercise performance. Thus, it is desirable to attenuate muscle soreness and fatigue and promote recovery... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Post-exercise muscle soreness and fatigue can negatively affect exercise performance. Thus, it is desirable to attenuate muscle soreness and fatigue and promote recovery even for daily exercise habits aimed at maintaining or improving health.
METHODS
This study investigated the effects of dietary collagen peptides (CPs) on post-exercise physical condition and fitness in healthy middle-aged adults unfamiliar with exercise. Middle-aged males ( = 20, 52.6 ± 5.8 years) received the active food (10 g of CPs per day) or the placebo food for 33 days in each period of the randomized crossover trial (registered at the University Hospital Medical Information Network Clinical Trials Registry with UMIN-CTR ID of UMIN000041441). On the 29th day, participants performed a maximum of five sets of 40 bodyweight squats. Muscle soreness as the primary outcome, fatigue, the maximum knee extension force during isometric muscle contraction of both legs, the range of motion (ROM), and the blood level of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) were assessed before and after the exercise load.
RESULTS
The analysis set was the per-protocol set ( = 18, 52.6 ± 6.0 years) for efficacy and the full analysis set ( = 19, 52.8 ± 5.9 years) for safety. The visual analog scale (VAS) of muscle soreness immediately after the exercise load was significantly lower in the active group than in the placebo group (32.0 ± 25.0 mm versus 45.8 ± 27.6 mm, < 0.001). The VAS of fatigue immediately after the exercise load was also significantly lower in the active group than in the placebo group (47.3 ± 25.0 mm versus 59.0 ± 22.3 mm, < 0.001). Two days (48 hours) afterthe exercise load, muscle strength was significantly higher in the active group than in the placebo group (85.2 ± 27.8 kg versus 80.5 ± 25.3 kg, = 0.035). The level of CPK did not change over time. The level of LDH increased slightly but was not different between the groups. No safety-related issues were observed.
CONCLUSIONS
These results showed that dietary CPs alleviated muscle soreness and fatigue and affected muscle strength after exercise load in healthy middle-aged males.
Topics: Adult; Male; Middle Aged; Humans; Myalgia; Cross-Over Studies; Exercise; Diet; Fatigue; Muscle, Skeletal; Dietary Supplements
PubMed: 37133292
DOI: 10.1080/15502783.2023.2206392 -
Frontiers in Cardiovascular Medicine 2024Fabry disease (FD) is a lysosomal storage disorder due to the impaired activity of the -galactosidase A (GLA) enzyme which induces Gb3 deposition and multiorgan... (Review)
Review
Fabry disease (FD) is a lysosomal storage disorder due to the impaired activity of the -galactosidase A (GLA) enzyme which induces Gb3 deposition and multiorgan dysfunction. Exercise intolerance and fatigue are frequent and early findings in FD patients, representing a self-standing clinical phenotype with a significant impact on the patient's quality of life. Several determinants can trigger fatigability in Fabry patients, including psychological factors, cardiopulmonary dysfunctions, and primary alterations of skeletal muscle. The "metabolic hypothesis" to explain skeletal muscle symptoms and fatigability in Fabry patients is growing acknowledged. In this report, we will focus on the primary alterations of the motor system emphasizing the role of skeletal muscle metabolic disarrangement in determining the altered exercise tolerance in Fabry patients. We will discuss the most recent findings about the metabolic profile associated with Fabry disease offering new insights for diagnosis, management, and therapy.
PubMed: 38327490
DOI: 10.3389/fcvm.2024.1341590 -
International Journal of Molecular... Jan 2024Patients suffering from chronic fatigue syndrome (CFS) or post-COVID syndrome (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial...
Patients suffering from chronic fatigue syndrome (CFS) or post-COVID syndrome (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial function and morphology may play a pivotal role. Thus, we aimed to measure the muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity and assess mitochondrial morphology in CFS and PCS patients in comparison to healthy controls (HCs). Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers using high-resolution respirometry. Mitochondrial morphology (subsarcolemmal/intermyofibrillar mitochondrial form/cristae/diameter/circumference/area) and content (number and proportion/cell) were assessed via electron microscopy. Analyses included differences in OXPHOS between HC, CFS, and PCS, whereas comparisons in morphology/content were made for CFS vs. PCS. OXPHOS capacity of complex I, which was reduced in PCS compared to HC. While the subsarcolemmal area, volume/cell, diameter, and perimeter were higher in PCS vs. CFS, no difference was observed for these variables in intermyofibrillar mitochondria. Both the intermyofibrillar and subsarcolemmal cristae integrity was higher in PCS compared to CFS. Both CFS and PCS exhibit increased fatigue and impaired mitochondrial function, but the progressed pathological morphological changes in CFS suggest structural changes due to prolonged inactivity or unknown molecular causes. Instead, the significantly lower complex I activity in PCS suggests probably direct virus-induced alterations.
Topics: Humans; Fatigue Syndrome, Chronic; COVID-19; Mitochondria, Muscle; Mitochondria; Muscle Fibers, Skeletal
PubMed: 38338957
DOI: 10.3390/ijms25031675