Aging may be contagious… not from one person to another, but from one organ to another. This could explain why dysfunction in one organ can promote dysfunction in other organs. This is particularly the case with acute liver failure, a serious liver dysfunction caused by an infection or a toxic product (alcohol, medication, etc.). These fulminant hepatitis often lead to problems in other organs, such as kidney failure and encephalopathies, which affect the brain. A study published on November 13, 2024 in the journal Nature Cell Biology by researchers from the Universities of Glasgow and Edinburgh in Scotland shows that these liver failures accelerate cellular ageing of the liver. This then leads to premature ageing of the kidney and brain, which could contribute to their dysfunction.
Aging of liver cells causes aging of other organs
To study liver failure, the researchers used a mouse model genetically modified to no longer regulate the p53 protein, which participates in the control of the cell cycle, in hepatocytes (majority cells of the liver). This modification caused the accumulation of p53, pushing these cells towards senescence, a stage typical of aging cells, when the cell cycle is blocked and the cell can no longer divide. This aging Premature liver cell death was accompanied shortly after by the same phenomenon in the kidney, brain and lungs of mice, while only hepatocytes had this modification.
The aging of kidney cells was followed by dysfunction of this organ. The same for the brain: the mice presented cognitive disorders and dysfunction of the hippocampus, a structure that plays a role in memory, among other things. Similar damage was also observed in people with acute hepatitis: the higher the level of senescence in the liver, the more these people had kidney and brain problems, and the higher their risk of death. Confirming these results in patients gives us the opportunity to identify markers in the blood that can indicate which people are most at risk of developing dysfunction in other organs and dying from serious liver problems," hopes one of the study's authors, professor of hepatology at University College London, Rajiv Jalan.
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Aging travels through the blood
To elucidate the mode of transmission of this senescence, the researchers looked closely at the expression of genes in the livers of these mice. This highlighted the activation of several genes involved in the pro-inflammatory response characteristic of senescent cells. This response is a way of signaling the immune system of the presence of these aging cells to facilitate their elimination. But the proteins generated by this response can travel through the blood and reach distant organs. Indeed, the blood of mice with failing livers showed an increase in the level of several of these proteins. This is how senescent cells in the liver could affect the kidneys and other organs.
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To test this hypothesis, the researchers treated cells from non-genetically modified mice with plasma (the liquid part of the blood) from mice engineered to have dysfunctional livers. Soon after, these cells began to acquire characteristics of senescent cells. That is, senescence in liver cells could cause senescence in other organs through the blood. This could be the way in which a serious disease in one organ can spread and affect other organs in the body, explains the study's director, Tom Bird, in a communicates. This knowledge can also teach us how to avoid it, For sudden illnesses such as acute liver failure, but also for diseases longer, related to age.
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