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.