Liver cell aging can cause multiorgan failure

The aging and cell destruction that occurs when the liver is damaged can spread to other organs, according to a new study conducted in mice and humans by scientists from the University of California, University of Edinburgh and CRUK Scotland Institute.

In the study, published in the journal Nature Cell Biology, the scientists demonstrated for the first time that cell destruction in a damaged liver can activate a process associated with aging and dysfunction, which is then passed on to healthy organs in other parts of the body.

The team also identified a key protein that, by targeting it, can prevent such multi-organ failure.

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

“Our results provide the first insight into why severe liver damage leads to failure of other organs, such as the brain and kidneys, and death. We were able to confirm these new and exciting observations in patients, paving the way for the development of blood biomarkers that can be measured to identify people at risk and new treatments for severe liver disease,” said Prof. Rajiv Jalan, study author from the UCLA Department of Medicine.

As the body ages, cells become fatigued and stop working efficiently. This process, called cellular aging, is a common manifestation of aging, but can also be triggered by diseases at any stage of life.

Aging liver cells after acute severe illness, which can be caused by a number of reasons including viral infections or toxins, overdose of paracetamol and other drugs, can cause irreversible damage, lead to liver failure and often multi-organ failure.

The study observed that once a large enough number of liver cells were damaged in mice with sudden liver failure, aging began to manifest itself in other organs, including the kidneys, lungs and brain, causing failure.

The researchers identified a key biological pathway involving TGFβ, a protein associated with the immune system, blocking which prevented the spread of aging liver cells to other organs in mice.

In the future, treatments that block this pathway could prevent the development of multi-organ failure in patients with severe liver damage, experts said.

The level of liver cell senescence was also a powerful indicator of disease outcome in patients with severe liver damage.

The research team studied liver tissue biopsies from 34 people with acute severe liver disease. High levels of liver cell aging in the early stages of the disease were associated with an increased risk of multi-organ failure and the need for liver transplantation.

There are currently no tests to predict how sudden liver failure will progress when it starts. Monitoring the ageing of liver cells could help identify people most at risk, including those most likely to need a liver transplant, says the research team.

The study’s principal investigator, Professor Tom Bird, from the University of Edinburgh’s Centre for Inflammation Research and Scotland’s CRUK Institute, said: “The implications of the findings are potentially very profound. They show the mechanism by which severe disease, even in one organ, can lead to the failure of many organs in the body. And it may also teach us how to prevent this from happening, both in a sudden illness and perhaps in a range of diseases that develop over many years or even decades as we age.”

The results of this study open up new ways of understanding diseases that arise during aging.