GDF15 and muscle function in cancer cachexia: a review
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.
Effects of mitochondrial transplant therapy on the reparation of injured skeletal muscle
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.
Exercise, nutrition, or combined interventions: which is the most effective treatment for sarcopenia?
No pharmacologic intervention has yet been approved for the treatment of sarcopenia. Only exercise and nutritional support via increased protein intake have been shown to significantly improve this condition. As such, lifestyle interventions aiming to increase physical exercise and/or protein intake are recommended for the prevention, management, and treatment of sarcopenia.
The aim of this systematic review was to assess the intervention (exercise or nutrition alone, against a combination of both) best able to improve sarcopenia. This improvement was measured in older adults using the skeletal muscle index (SMI), handgrip, and gait speed.
Current sarcopenia definitions and clinical outcomes: a need for homogeneity?
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.
2022: A year of research in JCSM
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.
Explaining and combatting the knowledge gaps surrounding sarcopenia
Sarcopenia is characterised by an age-related decline in muscle mass and strength combined with impairments in physical function. The risk of falls, fractures, and death is doubled in individuals with sarcopenia compared to those without. This patient population also frequently possesses comorbid diseases, including diabetes, cardiovascular disease, dementia, and chronic obstructive pulmonary disease. This may significantly increase their risk of suffering adverse outcomes post-surgery.
The aim of this editorial was to expose the serious nature of sarcopenia and underscore associated knowledge gaps in clinical practice.
The inflammatory response in muscle homeostasis and plasticity: a review
Around half of a healthy person’s body weight is made up of skeletal muscle. This type of muscle is able to demonstrate high levels of plasticity. In muscle homeostasis, as well as repair processes, there are satellite cells and inflammatory cells which play key roles. However, if the recruitment of inflammatory cells is not carefully controlled, muscle atrophy and fibrosis may occur, leading to muscle function impairment. Hence, the inflammation occurring in muscle repair as a double-edged sword. This is because inflammatory mediators play a role in fighting pathogens as well as in the formation of mature myofibres, but may also cause damage to the muscle. For example, inflammation is also associated with cachexia - specifically, there is a correlation between cachexia and high levels of circulating cytokines.
This paper also ends with a summary of approaches to treating muscle wasting disorders, such as cachexia, discussing exercise, nutritional interventions and targeting inflammatory pathways.
This review by Bouredji Z et al. aimed to discuss inflammation in muscle homeostasis and repair, as well as some management approaches to muscle wasting disorders such as cachexia.
The bone-muscle connection in breast cancer: a review
Breast cancer treatments often lead to musculoskeletal morbidity; muscle loss in general is seen as a complication of breast cancer, affecting survival and quality of life. Emerging new research into the biochemical and molecular links between the skeletal and muscular systems is beginning to be taken into account, alongside the well-known anatomical relationship, to improve our understanding of these effects. This paper discussed treatments such as anti-oestrogen therapy, which deteriorates bone health and muscle mass, and the significance of these effects in lower survival rates and worse outcomes for patients. In this sense, exercise is concluded to be of aid for patients with breast cancer in improving their outcomes.
This review by Ballinger T et al. aimed to understand the relevance of musculoskeletal health to breast cancer, and the strategies that could aid patients in this disease.