Aged cells in one diseased organ can spread, causing the failure of other organs

For the first time, researchers have discovered that the accumulation of aged and failing cells, called senescent cells, in one diseased organ can spread to multiple healthy organs, causing them to fail. The findings have opened the door to preventing multi-organ - or even age-related - disease.

There has been much interest recently in senescent cells and how these tired and ineffective cells are associated with aging and can affect our overall health. Over the years, we've covered research into the effect senescent cells have on things like lower back pain and hair growth.

Now, a new study led by the University of Edinburgh and Cancer Research UK (CRUK) Scotland Institute has demonstrated for the first time that once a large enough number of senescent cells have accumulated in one sick organ, the liver, they can spread to multiple healthy organs, causing them to fail.

"Our findings provide the first insight into why severe liver injury results in the failure of other organs, such as the brain and kidneys, and death," said Professor Rajiv Jalan, a liver disease specialist at University College London and one of the study's co-authors. "We were able to validate these novel and exciting observations in patients, providing a route to develop biomarkers that can be measured in the blood to identify those at risk, and new therapies to treat severe liver disease."

Studies have shown that senescence in liver cells is highly indicative of underlying disease. As such, it's an important area for developing targeted treatment. In the present study in mice, the researchers found that liver senescence progressed to failure in other organs, such as the kidneys, lungs, and brain. By investigating the interaction between liver senescence and kidney function, particularly, they were able to show that a "critical mass" needed to be reached before the senescence spread to other organs.

To see whether these findings were relevant to human disease, the researchers examined 34 patients with severe acute liver failure. They found that elevated levels of biomarkers of liver cell senescence - taken from a biopsy - predicted disease outcome, the need for liver transplantation, and the failure of other organs.

"The implications of the findings are potentially very profound," said Professor Tom Bird from the University of Edinburgh's Center for Inflammatory Research and the CRUK Scotland Institute and the corresponding author of the study. "This may be a means by which severe disease, even in a single organ, can snowball into the failure of many organs in the body. But it can also teach us about ways to prevent this happening, both in sudden disease and potentially in a range of diseases occurring over years or even decades as we age."

The researchers identified a biological pathway involving transforming growth factor beta (TGF-beta), a protein produced by white blood cells that plays a role in the immune system. When the pathway was blocked in mice, it prevented liver senescence from spreading to other organs.

"This is an exciting set of findings, unlocking crucial new insights with the potential to transform our understanding of multi-organ failure," said Morag Foreman, head of discovery research at the Wellcome Trust, a London-based charitable research foundation that partly funded the study. "This opens new avenues of research into how our cells break down that could help us treat and prevent sudden, or even age-related disease."