#cachexia

Motivation Drain

When a person feels ill, their mental and physical motivation can often diminish. Short term, such feelings may be beneficial, promoting rest and recuperation. But, with chronic illnesses, the reduced motivation may develop into severe apathy and depression – an extreme version of this being seen in cancer patients with cachexia (wasting syndrome). Recently, scientists have identified the brain circuitry behind this illness-induced motivation slump. Using a mouse model of cachexia, they showed that the neurons (green) of a brain region called the area postrema (pictured) were responsive to interleukin 6 – an inflammatory cytokine (type of small protein) found at unusually high levels in cachexia. In turn, these neurons inhibited the release of the feel-good factor dopamine in a key part of the brain’s reward system – thus sapping the animals’ drive. Importantly, blocking this inflammation-neuronal circuitry, restored motivation in the cachectic mice, providing hope that such a strategy might benefit cancer patients too.

Written by Ruth Williams

Image by Aelita Zhu, Washington University in St. Louis - from work by Xiaoyue Aelita Zhu (朱晓悦) & Sarah Starosta et al

Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA

Image copyright held by Washington University in St. Louis

Research published in Science, April 2025

Controlling Waste

Elucidating the genes involved in early Fruit fly model of cancer-associated muscle wasting or cachexia used to identify key regulators of glucose metabolism – their imbalance induces muscle degradation

Read the published research paper here

Image from work by Pedro Saavedra and colleagues

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, August 2023

Wasting Away

Skeletal muscles connect to your bones. They allow you to perform a wide range of different movements and functions, and also make up a significant portion of your body mass. But as we get older, our muscles get weaker, but we don’t really know why that happens. There are also a range of other conditions that lead to muscle wastage like cancer or diabetes. Crucially, muscle weakening isn’t just a symptom of these conditions, it contributes to mortality. In fact, preventing the loss of skeletal muscle mass increased survival in mice with cancer. The key question is how can we prevent wastage? Researchers studied the gene Deaf1 in fruit flies and found that too much Deaf1 activity caused a decrease in muscle size (right; compare areas outlined in white). By understanding how the size of muscle fibres is regulated we can find ways to age more healthily.

Written by Sophie Arthur

Image adapted from work by Flavia A. Graca and colleagues

Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in PLOS Genetics, November 2021

Consumed by Cancer

In the late stages of cancer, patients sometimes suffer from extreme muscle deterioration and weight loss– a condition known as cachexia. But, whether this tissue degradation is advantageous to the cancer or merely a consequence of disease was not clear. Studies of tumour growth in fruit flies now suggest that indeed cancers dismantle muscle to make themselves stronger. The development of certain tumours in the flies caused healthy muscle (left) to waste away (right), which fuelled both tumour growth and further muscle destruction. The tumours were found to produce a transporter protein that enabled them to suck up amino acids – protein building blocks – from the deteriorating muscle, and use them for their own growth. Researchers have also identified a compound that blocks the transporter and that, when fed to flies, inhibited tumour growth and prevented cachexia. The hope is that such a compound may have anticancer effects in humans too.

Read more about this research at the MRC LMS here

Written by Ruth Williams

Image from work by Holly Newton and colleagues

Metabolism and Cell Growth group, Medical Research Council London Institute of Medical Sciences, London, UK

Image copyright held by the original authors

Research published in Nature Communications, September 2020

In the Mind

Weight loss and overwhelming fatigue are traits we associate with severe illness. They can be symptoms of cachexia, a wasting disorder common in AIDS, heart failure, and cancer patients. Appetite loss and fatigue are largely controlled by the brain, but it’s not clear what prompts cachexia. To investigate a theory that it's caused by malfunctioning immune cells, until recently not thought to be able to access the brain, researchers studied mice with pancreatic cancer. They found neutrophils, a type of immune cell (pictured), in the mouse brain, along with high levels of a protein called CCR2, involved in neutrophil movement. Blocking CCR2 prevented neutrophils entering the brain and reduced cachexia symptoms, but did not reduce levels of neutrophils elsewhere in the body, where they play important roles. If a drug could target CCR2 in humans, it might be able to counter cachexia without hampering the immune system’s essential work.

Written by Anthony Lewis

Image from work by Kevin G Burfeind and colleagues

Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, May 2020

The Scientific research Notes Of S. Sunkavally (years: 2002-2011).