Cell ageing in one organ can snowball into multi-organ failure

Scientists have shown for the first time that the deterioration of cells in a damaged liver can activate a process associated with ageing and impaired function, which then transmits to otherwise healthy organs elsewhere in the body.

They also identified a key protein that could be manipulated to prevent such multi-organ failure. 

The findings could have major implications for our understanding of how diseases in different parts of the body interact with each other, and what happens as people age, experts say.

As the body gets older, cells become tired and stop working effectively. This process – called cell senescence – is a common effect of ageing but can also be triggered by diseases at any stage of life. 

Senescence of liver cells following acute severe liver disease – which can be caused by a number of diseases including viral infections or toxins such as paracetamol overdose – can cause irreparable damage, leading to liver failure and can often lead to multi-organ failure.

The study, led by the University of Edinburgh and CRUK Scotland Institute, identified that in mice with sudden liver failure, once a large enough number of liver cells were damaged, senescence started to appear in other organs, including the kidneys, lungs and brain, causing them to fail.

Researchers identified a key biological pathway involving TGFβ – a protein linked to the immune system – which, when blocked in mice, prevented the senescence in liver cells from spreading to other organs. 

In the future, treatments to block this pathway could prevent multi-organ failure in patients with severe liver injury, experts say.

Levels of liver cell senescence were also a powerful indicator of disease outcome 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 early in disease were linked to an increased risk of multi-organ failure and the need for liver transplantation. 

There is currently no test to predict how sudden liver failure will progress when it begins. Monitoring liver cell senescence could help to identify those most at risk, including those likely to need a liver transplant, the research team says.

The study, principally funded by the Wellcome Trust and Cancer Research UK, is published in the journal Nature Cell Biology. 

The research team involved a collaboration between groups located at the CRUK Scotland Institute and those at Newcastle University and University College London.

This study was led by Tom Bird, Principal Investigator and also involved researchers David Baird and Eoin O' Sullivan who are part of David Ferenbach’s research group at the Centre for Inflammation Research, Institute of Regeneration and Repair, University of Edinburgh.