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.
Failing cells
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 Cancer Research UK 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.
Block spread
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.