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Reviewed articles

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

Tumour derived exosomes and cancer cachexia: a review

Exosomes are extracellular vesicles that contain cargo such as proteins, lipids, nucleic acids and more. Their function is to alter cell signalling in the cell it releases its cargo into. For example, exosomes have been seen to alter muscle and adipose tissue metabolism. This has led to the thought that they may be involved in cancer cachexia. Inhibiting tumour derived exosome release therefore may improve survival and cancer cachexia in patients. Specifically, tumour derived exosome micro-RNAs have been associated with muscle wasting and tumour presence. Furthermore, they may package inflammatory cytokines. This could play a causal role in cancer cachexia as increase cytokine circulation is thought to precede the loss of appetite in cachexia, holding a causal role in the disease progression. This review by Pitzer CR et al. aimed to summarise the potential involvement of tumour derived exosomes in cancer cachexia.

Sarcopenia, unpreparedness, and the developing world: an urgent concern?

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.

PIH and sarcopenia in COPD: a causal relationship?

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.

Latest treatments for cancer cachexia: a review

Currently, there are many interventions and treatments for cancer cachexia. Early nutritional intervention and care are essential to ensure that sufficient nutritional requirements are met for the patients. This includes oral nutrition where possible, as well as nutrition and exercise therapy. Furthermore, preventive care to minimise loss of skeletal muscle mass is vital. Pharmacological options are also available. These include many options, such as non-steroidal anti-inflammatory drugs, anti-cytokine therapy and eicosapentaenoic acid. Furthermore, steroids are often used for cachexia. However, they have limited effects are limited, so recently, anamorelin hydrochloride, a ligand with a similar action to that of ghrelin, was developed. It is used to treat weight loss by increasing appetite and has been approved for use in cachexia. Anamorelin hydrochloride holds great promise to function as an effective therapeutic drug for cancer cachexia. This review by Watanabe H & Oshima T aimed to review the current treatments of cancer cachexia, as well as anamorelin hydrochloride, a new and promising treatment.

Body composition in colorectal cancer: a review

Personalised therapy is a challenge in advanced colorectal cancer care. Much research has been carried out on prognostic and predictive markers of this disease, and a strong correlation was found between sarcopenia and survival in such patients. Currently, selecting personalised strategies for patients is based on very few parameters, not making sufficient use of all available clinical information. Therefore, this paper suggests that it is possible to use body composition and liver tumour burden through automated extraction from CT images. Such automated segmentation would allow one to extract prognostic parameters from the routine imaging data which is collected from patients. This could provide personalised survival modelling for colorectal cancer patients. Specifically, the inclusion of body composition as a factor holds great promise in improving current strategy making for patient care. This review by Keyl J et al. aimed to explore automated assessment of body composition and liver metastases from CT images can improve personalised risk assessment.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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