The aging and malfunctioning of cells that occurs when one part of the body is damaged can spread to other organs, a study has found. Scientists have shown for the first time that cell damage in a damaged liver can trigger a process associated with aging and dysfunction, and then spread to otherwise healthy organs in the body. They have also identified a key protein that could be manipulated to prevent such multi-organ failure. The findings could have significant implications for our understanding of how diseases in different parts of the body interact with each other and what happens in the aging process, according to experts.

Blocking a Sugnaling Pathway Could Prevent Multiple Organ Failure

As the body ages, cells become fatigued and no longer function properly. This process – known as cellular senescence – is a common effect of aging but can also be triggered by diseases at any stage of life. The senescence of liver cells after acute severe liver disease – which can be caused by a number of diseases, including viral infections or toxins such as acetaminophen overdose – can cause irreparable damage, leading to liver failure and often to multiple organ failure. The study, led by the University of Edinburgh and the CRUK Scotland Institute, found that in mice with sudden liver failure, once a large enough number of liver cells were damaged, senescence occurred in other organs, including the kidneys, lungs and brain, causing them to fail. The researchers identified an important biological pathway involving TGF-β – a protein related to the immune system – that, when blocked in mice, prevented the spread of senescence in liver cells to other organs.

In the future, treatments to block this pathway could prevent multiorgan failure in patients with severe liver damage, experts say. The degree of liver cell senescence was also a strong predictor of disease progression in patients with severe liver damage. The study team examined liver tissue biopsies from 34 people with acute severe liver disease. High levels of liver cell senescence at the onset of the disease were associated with an increased risk of multiorgan failure and the need for liver transplantation. Currently, there is no test that can predict how sudden liver failure will develop. Monitoring hepatocyte senescence could help identify those most at risk, including those who are likely to need a liver transplant, according to the research team.

New Therapies for the Treatment of Severe Liver Disease

The study, which was mainly funded by the Wellcome Trust and Cancer Research UK, was published in the journal Nature Cell Biology. The research team comprised a collaboration between groups from the CRUK Scotland Institute and Newcastle University and University College London. The study’s principal investigator, Professor Tom Bird of the University of Edinburgh’s Centre for Inflammation Research and the CRUK Scotland Institute, said: “The implications of the results are potentially very profound. This could be one way in which severe disease, even in a single organ, can lead to the failure of many organs in the body. But it can also teach us how to prevent this, both in the case of sudden illnesses and in the case of a series of illnesses that occur over the years or even decades with increasing age.”

These results provide the first insights into why severe liver damage leads to the failure of other organs, such as the brain and kidneys, and to death. The researchers were able to validate these new and exciting observations in patients, thus demonstrating a way to develop biomarkers that can be measured in the blood to identify patients at risk, as well as new therapies to treat severe liver disease.