Reviewed articles

Explore our in-depth reviewed articles on sarcopenia, cachexia, and wasting disorders - conditions associated with muscle loss and functional decline.

Frailty From the literature

Are immunosenescence and mitochondrial dysfunction hallmarks of frailty?

The development of frailty has been attributed to a number of biological mechanisms, including immunosenescence and mitochondrial dysfunction. Impairments in immune cell mitochondria have been proposed to both cause and interact with immunosenescence, hypothetically leading to ageing-related increases in sterile inflammation, commonly known as ‘inflammaging’. However, despite the convincing evidence supporting these suggestions, claims regarding the effects of immunosenescence on clinical outcomes such as frailty have recently been challenged. The aim of this article was to examine the association between immunosenescence, mitochondrial dysfunction, and frailty syndrome in community-dwelling frail and non-frail older adults.

January 30, 2023

Cachexia Cancer cachexia From the literature Muscle

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.

January 20, 2023

Cachexia From the literature

Progressive development of cachexia in different organ systems: a review

Cachexia is defined as an unintentional loss of 5% or more of body weight, a complication which often negatively affects survival rates. Cachexia is caused by circulating cytokines in the body which are produced by cancer cells and immune cells, causing behavioural and systemic changes. However, how cachexia impacts different tissues is unknown; there is a large amount of information missing, as it is likely there are more tissues in the body affected by cachexia than we know. There are known differences in tissue wasting: in the heart, atrophy is seen after 2 weeks of tumour implantation, but very little wasting in any other tissues at this point. The heart and skeletal muscles are the tissues affected first and foremost. This study also discovered that tissues such as the brain which do not undergo wasting, experience functional derangement due to transcriptional changes such as the upregulation of angiotensin-converting enzyme (ACE). Using lisinopril, a drug which inhibits ACE, muscle force can be improved, even if wasting is not prevented. However, this study was completed on mice with no T lymphocytes - this is a limitation as T cells have been seen to induce or protect from cachexia, so more studies are needed to understand the involvement of T cells in cachexia. This review by Graca FA et al. aimed to summarise how cachexia affects different tissue systems in the body.

January 20, 2023

Frailty From the literature

Daily walking speed and frailty: a significant association?

Walking speed (WS) is clinically recognized as a crucial vital sign. Associations between daily walking speed (DWS) and health outcomes have been underscored by a number of studies, which have further recognized it as an accurate predictor of dependency and mortality in elderly individuals. Despite this knowledge, very few studies have examined the link between DWS and frailty. The aim of this study was to investigate a smartphone application’s ability to assess the association between DWS and frailty. This application measured DW parameters such as speed and step length and further conducted an in-app frailty assessment using the Kihon checklist.

January 16, 2023

From the literature Muscle

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.

January 16, 2023

Cancer From the literature Sarcopenia

Sarcopenia, perioperative mortality and advanced ovarian cancer: a review

All types of ovarian cancers hold a high risk of morbidity and mortality for the patients. Currently, there are many efforts to assess ovarian cancer progression, to allow for the development of accurate treatment and management plans for preventing mortality in the long-term. A physical indicator of increased vulnerability is frailty. Frailty can lead to falls, hospitalisation and increased risk of death. Generally, frailty is closely associated with poor prognosis and shorter progression-free survival in many conditions, including ovarian cancer. However, diagnosing frailty is complex, due to a lack of a set definition and due to comorbidities appearing in older patients. Although this study draws useful conclusions, its limitation holds that some confounding factors could not be adjusted for, meaning further research is needed to understand the interplay between ovarian cancer and frailty. This review by Can E et al. aimed to understand the prognostic value of frailty to predict complications and mortality in patients with ovarian cancer.

January 16, 2023

Cancer From the literature Nutrition

Nutrition and dietary supplements: a review

A consensus is held that all tumour patients should be offered the opportunity for regular screenings for nutritional disorders, and their results should be monitored. This is because after cancer treatments, there is a high risk of metabolic syndrome. Healthy diets and regular exercise can help with this. Nutritional disorders are a huge issue for cancer patients because almost half of all advanced tumour patients experience eating and weight loss issues - this increases the threat of cachexia. Food intake should be kept normal (not through enteral tube or parenteral feeding) for as much as possible, with good nutrition reducing the risk of tumour recurrence. In palliative cases, hunger and thirst should be subjectively satisfied to alleviate distress. This review by Arends J aimed to assess the role of nutrition in cancer patients, all the way to palliative cases.

January 16, 2023

Cancer From the literature Sarcopenia

Sarcopenia and age in cancer patients: a review

Currently, medical treatment for cancer is personalised by looking at genetic and molecular factors of cancer cells. However, for characterising patients, factors such as age, weight, BMI, comorbidities, etc are used. Hence, there is no set, universal variable(s) to be used in managing cancer. It is possible that this is the reason that many anticancer drugs perform poorly clinically, due to this variability between patients. One of the factors that can be used is chronological age, which defines the patient’s accumulated damage to their system. Age is an accurate predictor of various outcomes, including the outcomes of anticancer drug therapies. For example, patients between the ages of 65-69 are often less likely to respond well to chemotherapy. A way to index age is sarcopenia, but due to the complex, varying body compositions associated with tumour growth, it is difficult to use sarcopenia consistently as an index for age in cancer management. This review by Laviano A aimed to explore variables, such as sarcopenia and ageing, in their effects on cancer and anticancer drug successes.

January 9, 2023

Cancer From the literature Nutrition

Malnutrition in paediatric oncology: a review

Out of all non-accidental deaths in the United States, paediatric cancer is the number one cause of death. Of children with cancer, 80% experience malnutrition during their treatment programmes. This statistic is dangerous, as malnutrition, as well as cachexia, worsen toxicity of treatment and the child’s quality of life. Yet, there are no standard definitions and nutritional interventions within clinical practice, with this varying between hospitals and clinicians on how to screen for and intervene with malnutrition. For example, some studies have explored Peptamen supplements for children with acute lymphoblastic leukaemia, whilst others tried isocaloric and hypercaloric supplements. Overall, there is a significant lack of nutrition-based studies in paediatric oncology patients. Yet, overall, it has been seen that nutritional interventions in general are seen to increase the patient’s weight and decrease the risk of complications during treatment. Furthermore, incorporating nutritional screening into the patient’s management decreases their risk for malnutrition. This review by Franke J et al. aimed to explore the current available malnutrition screening and intervention methods across different hospitals and studies for childhood cancer, and to underscore the lack of a standard management system.

January 9, 2023

Exercise From the literature Muscle Sarcopenia

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.

January 5, 2023

From the literature Muscle Sarcopenia

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.

January 5, 2023

Cachexia Cancer From the literature Muscle Sarcopenia

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.

January 4, 2023

Frailty From the literature

Frailty as a predictive metric for pre- and post-transplant outcomes

Frailty is a known risk factor for negative surgical outcomes, and the Liver Frailty Index (LFI) has been shown to predict mortality in patients awaiting liver transplants. Despite this, neither a diagnosis of frailty nor a patient’s LFI holds any weight when determining their position on liver transplant waitlists. The aim of this article was to assess frailty and the LFI’s ability to predict pre- and post-transplant outcomes.

January 2, 2023

Ageing From the literature Muscle Sarcopenia

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.

January 2, 2023

Cachexia From the literature Muscle

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.

January 2, 2023

Cachexia Cancer Cancer cachexia Frailty From the literature

Review of the endocrine organ-like tumour hypothesis of cancer cachexia in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma, PDAC, is one of the most fatal types of solid tumours. It is also linked to a high prevalence of cachexia, with around 80% of PDAC patients exhibiting cachexia. There is one hypothesis, the endocrine organ–like tumour hypothesis, which aims to explain the reasons behind cancer cachexia occurring during pancreatic ductal adenocarcinoma. Some of the reasons include metabolites, epigenetic changes, hormonal disturbance and genetic instability may be behind the development of cancer cachexia. Generally, the belief is held that metabolic disruption is the process behind cachexia development, but it is also believed there is not one single factor that triggers it. This review by Yu Y et al aimed to synthesise an understanding of cancer cachexia development and the response of cachexia to current available treatments.

December 20, 2022