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1.
Therapeutic approaches to preserve the musculature in Duchenne Muscular Dystrophy: The importance of the secondary therapies.
Angelini, G, Mura, G, Messina, G
Experimental cell research. 2022;(2):112968
Abstract
Muscular dystrophies (MDs) are heterogeneous diseases, characterized by primary wasting of skeletal muscle, which in severe cases, such as Duchenne Muscular Dystrophy (DMD), leads to wheelchair dependency, respiratory failure, and premature death. Research is ongoing to develop efficacious therapies, particularly for DMD. Most of the efforts, currently focusing on correcting or restoring the primary defect of MDs, are based on gene-addition, exon-skipping, stop codon read-through, and genome-editing. Although promising, most of them revealed several practical limitations. Shared knowledge in the field is that, in order to be really successful, any therapeutic approach has to rely on spared functional muscle tissue, restricting the number of patients eligible for clinical trials to the youngest and less compromised individuals. In line with this, many therapeutic strategies aim to preserve muscle tissue and function. This Review outlines the most interesting and recent studies addressing the secondary outcomes of DMD and how to better deliver the therapeutic agents. In the future, the effective treatment of DMD will likely require combinations of therapies addressing both the primary genetic defect and its consequences.
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2.
A new paradigm in sarcopenia: Cognitive impairment caused by imbalanced myokine secretion and vascular dysfunction.
Jo, D, Yoon, G, Kim, OY, Song, J
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112636
Abstract
Sarcopenia characterized by reduced skeletal muscle mass and decreased muscle strength is increasing in prevalence globally. The pathophysiology of sarcopenia is related to various factors including hormonal imbalance, increased intracellular oxidative stress, reduction of food intake, advanced age, low body mass index, and low physical activity. Recently, sarcopenia has been reported to be associated with cognitive decline, and the common risk factors between sarcopenia and memory loss were observed in cohort studies. Many researchers suggested that the prevalence of sarcopenia is associated with vascular disorder, such as atherosclerosis and alteration of intracellular mechanisms caused by changes in myokine secretion. We herein review the emerging evidence on the strong link between cognitive impairment and sarcopenia, focusing on myokine secretion and vascular dysfunction, and provide an understanding of the relevant mechanisms and crucial determinants in cognitive decline caused by sarcopenia.
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3.
The Impact of Vegan and Vegetarian Diets on Physical Performance and Molecular Signaling in Skeletal Muscle.
Pohl, A, Schünemann, F, Bersiner, K, Gehlert, S
Nutrients. 2021;(11)
Abstract
Muscular adaptations can be triggered by exercise and diet. As vegan and vegetarian diets differ in nutrient composition compared to an omnivorous diet, a change in dietary regimen might alter physiological responses to physical exercise and influence physical performance. Mitochondria abundance, muscle capillary density, hemoglobin concentration, endothelial function, functional heart morphology and availability of carbohydrates affect endurance performance and can be influenced by diet. Based on these factors, a vegan and vegetarian diet possesses potentially advantageous properties for endurance performance. Properties of the contractile elements, muscle protein synthesis, the neuromuscular system and phosphagen availability affect strength performance and can also be influenced by diet. However, a vegan and vegetarian diet possesses potentially disadvantageous properties for strength performance. Current research has failed to demonstrate consistent differences of performance between diets but a trend towards improved performance after vegetarian and vegan diets for both endurance and strength exercise has been shown. Importantly, diet alters molecular signaling via leucine, creatine, DHA and EPA that directly modulates skeletal muscle adaptation. By changing the gut microbiome, diet can modulate signaling through the production of SFCA.
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4.
Alteration of Flavin Cofactor Homeostasis in Human Neuromuscular Pathologies.
Tolomeo, M, Nisco, A, Barile, M
Methods in molecular biology (Clifton, N.J.). 2021;:275-295
Abstract
The aim of this short review chapter is to provide a brief summary of the relevance of riboflavin (Rf or vitamin B2) and its derived cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) for human neuromuscular bioenergetics.Therefore, as a completion of this book we would like to summarize what kind of human pathologies could derive from genetic disturbances of Rf transport, flavin cofactor synthesis and delivery to nascent apoflavoproteins, as well as by alteration of vitamin recycling during protein turnover.
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5.
Muscle-strengthening activities and risk of cardiovascular disease, type 2 diabetes, cancer and mortality: A review of prospective cohort studies.
Giovannucci, EL, Rezende, LFM, Lee, DH
Journal of internal medicine. 2021;(4):789-805
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Abstract
The benefits of aerobic moderate-to-vigorous physical activity (MVPA) on major non-communicable diseases (NCDs) are well established. However, much less is known whether muscle-strengthening activities (i.e., resistance/weight/strength training) confer similar benefits. Herein, we conducted a narrative literature review and summarized the existing evidence from large prospective cohort studies on muscle strengthening activities and risk of major chronic diseases and mortality in adults generally free of major NCDs at baseline. Current epidemiologic evidence suggests that engagement in muscle-strengthening activities over 1-2 sessions (or approximately 60-150 min) per week was associated with reduced risk of cardiovascular disease (seven studies; approximately 20%-25% reduction), type 2 diabetes (four studies; approximately 30% reduction), cancer mortality (four studies; approximately 15%-20% reduction) as well as all-cause mortality (six studies; approximately 20%-25% reduction). For diabetes, the risk appears to lower further with even higher levels of muscle-strengthening activities, but some studies for cardiovascular and all-cause mortality suggest a reversal whereby higher levels (≥2.5 h/week) have less benefit, or are even harmful, relative to lower levels of activity. The likely mechanisms contributing to a benefit include improvement in body composition, lipid profile, insulin resistance and inflammation. The evidence supports engaging in 1-2 sessions (up to 2.5 h) per week, preferably performed complementary to the recommended levels of aerobic MVPA. Although data are limited, caution is suggested for training exceeding 2.5 h per week. Further studies are required to better understand the influence of frequency, duration and intensity of muscle-strengthening activities on major NCDs and mortality in diverse populations.
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6.
The clinical relevance and mechanism of skeletal muscle wasting.
Duan, K, Gao, X, Zhu, D
Clinical nutrition (Edinburgh, Scotland). 2021;(1):27-37
Abstract
Skeletal muscle wasting occurs in both chronic and acute diseases. Increasing evidence has shown this debilitating process is associated with short- and long-term outcomes in critical, cancer and surgical patients. Both muscle quantity and quality, as reflected by the area and density of a given range of attenuation in CT scan, impact the patient prognosis. In addition, ultrasound and bioelectrical impedance analysis (BIA) are also widely used in the assessment of body composition due to their bedside viability and no radioactivity. Mechanism researches have revealed complicated pathways are involved in muscle wasting, which include altered IGF1-Akt-FoxO signaling, elevated levels of myostatin and activin A, activation of NF-κB pathway and glucocorticoid effects. Particularly, central nervous system (CNS) has been proven to participate in regulating muscle wasting in various conditions, such as infection and tumor. Several promising therapeutic agents have been under developing in the treatment of muscle atrophy, such as myostatin antagonist, ghrelin analog, non-steroidal selective androgen receptor modulators (SARMs). Notably, nutritional therapy is still the fundamental support in combating muscle wasting. However, the optimizing and tailored nutrition regimen relies on accurate metabolism measurement and large clinical trials in the future. Here, we will discuss the current understanding of muscle wasting and potential treatment in clinical practice.
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Evidence for the Contribution of Gut Microbiota to Age-Related Anabolic Resistance.
Watson, MD, Cross, BL, Grosicki, GJ
Nutrients. 2021;(2)
Abstract
Globally, people 65 years of age and older are the fastest growing segment of the population. Physiological manifestations of the aging process include undesirable changes in body composition, declines in cardiorespiratory fitness, and reductions in skeletal muscle size and function (i.e., sarcopenia) that are independently associated with mortality. Decrements in muscle protein synthetic responses to anabolic stimuli (i.e., anabolic resistance), such as protein feeding or physical activity, are highly characteristic of the aging skeletal muscle phenotype and play a fundamental role in the development of sarcopenia. A more definitive understanding of the mechanisms underlying this age-associated reduction in anabolic responsiveness will help to guide promyogenic and function promoting therapies. Recent studies have provided evidence in support of a bidirectional gut-muscle axis with implications for aging muscle health. This review will examine how age-related changes in gut microbiota composition may impact anabolic response to protein feeding through adverse changes in protein digestion and amino acid absorption, circulating amino acid availability, anabolic hormone production and responsiveness, and intramuscular anabolic signaling. We conclude by reviewing literature describing lifestyle habits suspected to contribute to age-related changes in the microbiome with the goal of identifying evidence-informed strategies to preserve microbial homeostasis, anabolic sensitivity, and skeletal muscle with advancing age.
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8.
[Sarcopenia - 2021: Pathophysiology, diagnosis, therapy].
Pár, A, Hegyi, JP, Váncsa, S, Pár, G
Orvosi hetilap. 2021;(1):3-12
Abstract
Összefoglaló. A sarcopenia progresszív, generalizált vázizombetegség az izomtömeg fogyásával és az izomfunkció romlásával, számos szövődménnyel, rossz prognózissal. A sarcopeniát eredetileg életkorfüggő, idősekben jelentkező kórképnek írták le (primaer sarcopenia). Később derült ki, hogy fiatal- és középkorú személyeknél is előfordul, különböző betegségekhez társulva (secundaer sarcopenia). A közlemény áttekintést ad a betegség patofiziológiájáról, a fizikai inaktivitás, az inzulinrezisztencia, a krónikus gyulladás, a citokinek, hepatokinek és miokinek szerepéről az izomkárosodásban, valamint az izom, a zsírszövet és a máj funkcionális kapcsolatairól nem alkoholos zsírmájban és cirrhosisban. A diagnózis felállítását számos funkcionális próba, illetve vizsgálóeljárás teszi lehetővé. Az izomerő-csökkenés igazolása a legfontosabb paraméter (kézszorító erő). Az izomtömegvesztést kettős energiájú röntgenabszorpciometria, bioelektromosimpedancia-analízis, komputertomográfia vagy mágneses rezonanciás képalkotó vizsgálat mutathatja ki, megerősítve a kórismét, a fizikai teljesítmény csökkenése pedig a sarcopenia súlyosságát jelzi. A sarcopenia kezelése és a progresszió prevenciója a fiatalkorban elkezdett és élethosszig tartó rendszeres fizikai aktivitáson, a protein-kalória túltápláláson és a gyógyszeres terápián alapul, beleértve a D-vitamin és a tesztoszteron pótlását, az elágazó láncú aminosavak és az L-karnitin adását. Másodlagos sarcopeniában az alapbetegség kezelése is szükséges. Orv Hetil. 2021; 162(1): 3-12. Summary. Sarcopenia is a progressive, generalized skeletal muscle disease with the loss of muscle mass and function, associated with adverse outcomes and poor prognosis. Sarcopenia first was regarded as an age-related disorder of older people (primary sarcopenia). Later it turned out that it can also occur in young age due to a range of chronic disorders such as cancer, anorexia or malnutrition (secondary sarcopenia). This paper overviews the pathophysiology of sarcopenia and the factors involved in the muscle mass loss, i.e., physical inactivity, insulin resistance, low-grade chronic inflammation, hepatokines and myokines. The basic feature is the imbalance between proteolysis and protein synthesis that leads to muscle atrophy. We discuss the relationship between liver, muscle and adipose tissue in non-alcoholic fatty liver disease and cirrhosis. To diagnose sarcopenia, there are a range of tests and tools that measure muscle strength and muscle mass as well as physical performance. The low muscle strength (hand grip strength) is the primary parameter of the diagnosis, the best measure of muscle function. The loss of skeletal muscle mass assessed by dual-energy X-ray absorptiometry, bioelectric impedance analysis, computer tomography, or magnetic resonance imaging confirms diagnosis, while the decrease in physical performance reflects severe sarcopenia. For the treatment and prevention of progression, the most important is the regular physical activity started from early adulthood, and healthy diet containing protein-calorie hyperalimentation. In addition, a pharmacotherapy with the supplementation of vitamin D and testosterone, furthermore, the administration of L-carnitine and branched-chain amino acids can be recommended. In the case of secondary sarcopenia, the underlying disease also requires treatment. Orv Hetil. 2021; 162(1): 3-12.
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9.
Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Elderly Body Composition and Muscle Strength: A Review of Clinical Trials.
Costa Riela, NA, Alvim Guimarães, MM, Oliveira de Almeida, D, Araujo, EMQ
Annals of nutrition & metabolism. 2021;(1):16-22
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Abstract
BACKGROUND The aging process has great impact on body composition, such as the increase of adipose tissue in abdominal region, and the decrease of lean body mass, due to skeletal muscle loss. A reduction in muscle mass is associated to high risk of fractures and falls, loss of mobility, and increased number of hospitalizations. Beta-hydroxy-beta-methylbutyrate (HMB) is a biological substance derived from leucine metabolism, with anabolic and anticatabolic properties. Some HMB effects are tissue repair stimulation and protein anabolism. AIMS We aimed to evaluate the effects of HMB supplementation on body composition and muscle strength in elderly, as well as to identify the efficient dosages to reach these effects. METHODS This review included studies that evaluated muscle mass and muscle strength, associated or not with physical exercise and diet in elderly people. Only studies published from 2008 to 2019 were selected for analysis. RESULTS Six articles were included in the review. The used doses varied from 1.5 to 3 g. In 5 studies, HMB supplementation was associated with calcium; only 1 study did not use the oral administration route. Two studies used 4 g of maltodextrin as a vehicle; 1 used HMB with a hypercaloric and hyperproteic supplement; 1 associated HMB with lysine and arginine; and 1 with arginine and glutamine. Supplementation of 3 g of HMB has shown to be most beneficial in improving strength and body composition in people over 65 years, especially in bed rest and untrained conditions. CONCLUSION Our findings suggest that HMB has a positive effect on body composition and strength, especially in bedridden or sedentary elderly, due to its anticatabolic properties.
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Prevalence and Nonpharmacological Interventions for Sarcopenia among Cirrhotic Patients.
Abdelbasset, WK, Nambi, G, Elsayed, SH, Moawd, SA, Ibrahim, AA, Verma, A, Tantawy, SA, Kamel, DM, Saleh, AK, Aldhafian, OR, et al
Disease markers. 2021;:8866093
Abstract
Sarcopenia is the most common feature of hepatic cirrhosis characterized by progressive loss of muscle mass and function and increases permanently the mortality and morbidity rates among those patients. The incidence of sarcopenia in cirrhotic patients ranged 40-70% associating with impaired quality of life and augmented rates of infection. Based on these issues, this review is aimed at determining the prevalence and main causes of sarcopenia among cirrhotic patients and recognizing the recent diagnostic and physical treatment modalities that prevent risk factors for sarcopenia in those patients. No ideal modality is currently demonstrated for diagnosing sarcopenia in hepatic diseases, particularly cirrhosis; however, recent studies reported different diagnostic modalities for muscle function in different individuals including handgrip strength, skeletal muscle index, six-min walk test, liver frailty index, short physical performance battery, and radiological assessments for quadriceps and psoas muscles. Exercise training and therapeutic nutrition are strongly recommended for controlling sarcopenia in cirrhotic patients. The exercise program is designed and carried out on a frequent basis within an extensive scheduled time aimed at improving functional performance, aerobic capacity, and healthy conditions. Finally, a combination of exercise training and therapeutic nutrition is powerfully recommended to control sarcopenia in cirrhosis.