With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages...
Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1-year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (P MRS) in a...
🗓️ 2024-04-13
📰 Publication: Journal Of Cachexia Sarcopenia And Muscle
Obesity, one of the most frequent health problems in the adult population, is a condition characterized by excessive white adipose tissue accumulation and accompanied by the increased risk to develop other disorders such as type II diabetes, cardiovascular disorders, physical...
Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with a complex pathophysiology. Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform...
🗓️ 2024-02-08
📰 Publication: International Journal Of Molecular Sciences
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...
This comprehensive review sheds light on cancer cachexia (CC), a significant condition marked by muscle wasting in cancer patients, emphasizing its molecular mechanisms and potential treatments. Highlighting the challenge CC presents, especially in older individuals, the article discusses the multifaceted approach needed to combat this syndrome.
This study investigates the connection between sarcopenia and age-related spinal deformities, focusing on lumbar paravertebral muscles (PVM) quality and volume. Results show that sarcopenic patients have higher ectopic fat infiltration in PVM, contributing to spinal deformities, highlighting the importance of understanding and addressing sarcopenia in relation to spinal health.
Muscle strength has recently been defined as sarcopenia’s main component by the revised European Working Group in Sarcopenia for Older People (EWGSOP2). This shift from muscle mass to strength has had transformative implications within clinical practice and has greatly facilitated sarcopenia’s diagnostic process. Despite this trailblazing consensus, sarcopenia remains an issue of growing concern throughout high-income countries (HICs). Although low- and middle-income countries (LMICs) are disproportionately affected by the threat of sarcopenia, their care providers and healthcare systems seem to be the least prepared to tackle it.
The aim of this article is to expose the state of sarcopenia awareness and management in LMICs. It further proposes solutions to prepare the developing world for this growing concern.
Nocturnal hypoxia commonly occurs in patients with chronic obstructive pulmonary disease (COPD), and in this context may be referred to as prolonged intermittent hypoxia (PIH). It is estimated that 1 in 5 COPD patients also suffer from sarcopenia, which may affect both respiratory and non-respiratory skeletal muscles and be causally linked to PIH. The presentation of sarcopenia alongside COPD is known to reduce quality of life and increase both hospitalisation and mortality rates in affected patients. Despite this, the adaptive cellular responses to PIH in skeletal muscle have not yet been adequately investigated.
The aim of this article was to discuss findings from a 2022 paper by Attaway and colleagues, which itself aimed to explore adaptive cellular responses to PIH.
In this study, TOV21G cancer cachexia mouse models were used to demonstrate impaired muscle function and performance which is seen in cachexia patients. With growth differentiation factor 15, GDF15, neutralization, the mice were seen to exhibit restored muscle function and performance. GDF15 is a stress-responsive cytokine which is secreted by many cells, including tumour cells and damaged cells. GDF15 functions by activating glial cell line-derived neurotrophic factor, GDNF, receptor GFRAL. This is expressed in the hindbrain and leads to reducing food intake and weight loss. This is relevant to cachexia patients, and patients with chronic diseases such as heart failure, as their GDF15 levels are significantly higher than that of healthy people. In this study, the mice were treated with mAB2, an anti-GDF15 antibody. They demonstrated weight gain in terms of fat mass and lean mass, improved muscle function and physical performance. Hence, it is thought that GDF15-related therapy may be effective for patients with cachexia. However, symptoms of cachexia such as fatigue do not appear to be related to GDF15 levels, so further exploration is necessary.
This review by Kim-Muller JY et al. aimed to explore how GDF15 levels are related to weight loss and highlight how GDF15 neutralization could be an option for treating cachexia.
It is known that traumatic muscle injury damages mitochondria, which may cause them to leak their contents into the cytoplasm and subsequently trigger calcium accumulation, cell death, endoplasmic reticulum stress, and the release of reactive oxygen species (ROS). The latter reduces mitochondrial quality and increases the number of unhealthy mitochondria present in the cell, which may delay post-injury muscle regeneration. Although this knowledge has informed studies demonstrating the beneficial effects of mitochondrial transplant therapy (MTT) on ischaemia-damaged myocardium, its effects on injured skeletal muscle remain undefined.
The aim of this article was to examine the effects of MTT on skeletal muscle function after neuromuscular injury. The latter was induced using BaCl2, which causes widespread muscle proteolysis via myofibre Ca2+ overload and hyper-contractions.
Three new definitions of sarcopenia have emerged in the past four years, proposed by the Sarcopenia Definition and Outcome Consortium (2020, SDOC), the European Working Group on Sarcopenia in Older People (2019, EWGSOP2) and the Asian Working Group on Sarcopenia (2019, AWGS2). No consensus on a unique definition of sarcopenia has yet been achieved, as the three new definitions proposed exhibit significant differences from each other. EWGSOP2’s definition of sarcopenia, for instance, characterises it as low muscle strength and mass, while the one developed by SDOC focuses on low muscle strength and gait speed instead.
The aim of this scoping review was to investigate all three recent sarcopenia definitions’ predictive validity for clinical outcomes.
The Journal of Cachexia, Sarcopenia and Muscle mainly publishes research on cachexia, sarcopenia and muscle wasting disorders, but also includes papers on cancer, heart failure, ageing and many other conditions. Before November 2022, there were seen to be 775,000 downloads of the articles within the journal, with the top three countries downloading articles being China, the US and Japan. The most downloaded and cited article is entitled, Cachexia as a major underestimated and unmet medical need: facts and numbers.
This review by Frohlich A et al. aimed to review the successes of the Journal of Cachexia, Sarcopenia and Muscle in 2022.
Muscle Wasting Disease (MWD) in Cachexia and Sarcopenia
Weight loss is the hallmark of any progressive acute or chronic disease state. In its extreme form, it involves a significant lean body mass (including skeletal muscle), and fat loss. Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Muscle wasting is related to a poor quality of life and increased morbidity/ mortality.
Two common but distinct conditions characterized by a loss of skeletal muscle mass are sarcopenia and cachexia. Sarcopenia, cachexia, and anorexic disorders (protein-energy malnutrition) represent the major causes of muscle-wasting disorders.
It has been known for millennia that muscle and fat wasting leads to poor outcomes including deaths in chronic disease states.
It is usually accompanied by physical inactivity, decreased mobility, slow gait, and poor physical endurance which are also common features of the frailty syndrome.
Fig. 1 – Framework for the suggested classification of MWD by disease etiology and disease progression.
Both cachexia and sarcopenia are characterized by an important muscle dysfunction that leads to increased morbidity and mortality.
Fig. 2 – The cachexia/ sarcopenia pyramid. Both lead to muscle dysfunction.
Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, et al. Cachexia: a new definition. Clin Nutr 2008; 27: 793–799.
Anker SD, Coats AJS, Morley JE, Rosano G, Bernabei R, Haehling S, et al. Muscle wasting disease: a proposal for a new disease classification. J Cachexia Sarcopenia Muscle 2014; 5: 1–3.
Argiles JM, Busquets S, Stemmler B, López-Soriano FJ. Cachexia and sarcopenia: mechanisms and potential targets for intervention. Current Opinion in Pharmacology 2015; 22: 100–106.
Bowen TS, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle 2015; 6: 197–207.
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