As people grow older, changes happen inside the body that are not always easy to see. Some of these changes can quietly raise the risk of serious disease.
Now, researchers at the Mayo Clinic have discovered an important clue about how aging cells may help drive a dangerous and increasingly common liver condition known as metabolic dysfunction-associated steatohepatitis, or MASH.
MASH is a severe form of fatty liver disease. It develops when fat builds up in the liver and then triggers long-lasting inflammation and scarring.
Over time, this damage can stop the liver from working properly. In the most serious cases, MASH can lead to liver failure or liver cancer, and many patients eventually need a liver transplant to survive. As obesity and metabolic diseases continue to rise around the world, doctors expect MASH to become even more common in the coming years.
In a study published in Nature Communications, the Mayo Clinic team focused on a group of aging cells often called “zombie cells.”
These cells are also known as senescent cells. They are cells that have stopped dividing but refuse to die. In younger people, the immune system usually clears these cells away. But as the body ages, zombie cells can build up and remain active inside tissues.
Even though they no longer divide, zombie cells are far from harmless. They release many substances that cause inflammation and damage nearby healthy cells. Scientists have long suspected that these aging cells play a role in age-related diseases, including liver disease, but the exact process has not been clear.
The research team, led by Dr. Stella Victorelli, discovered a key mechanism that explains how zombie cells can make liver disease worse. Inside every cell are tiny structures called mitochondria. These structures act like power plants, producing energy that keeps cells alive. Mitochondria also contain their own genetic material, known as mitochondrial RNA.
Under normal conditions, this RNA stays safely inside the mitochondria. But the researchers found that in zombie cells, mitochondrial RNA can leak out into the main part of the cell. When this happens, the cell becomes confused. It mistakes its own leaked RNA for a virus.
This triggers internal alarm systems called antiviral sensors. Two of these sensors are known as RIG-I and MDA5. These sensors normally activate when a virus enters a cell, telling the immune system to respond. In zombie cells, however, they are activated by the cell’s own leaked material. This false alarm sets off strong inflammation signals.
As a result, the liver becomes filled with inflammatory messages that harm surrounding healthy tissue. Over time, this ongoing inflammation leads to scarring, worsening liver function, and faster progression of MASH.
The researchers then tested what would happen if they blocked these sensors. When RIG-I and MDA5 were shut down, inflammation dropped sharply. This showed that the sensors play a central role in driving liver damage.
The team also discovered how the mitochondrial RNA escapes in the first place. Two proteins, called BAX and BAK, help open tiny pores in the membrane of the mitochondria.
These openings allow mitochondrial RNA to leak out. In a laboratory model that mimics MASH, blocking BAX and BAK stopped the RNA from escaping. This led to lower inflammation levels and healthier liver tissue.
Rather than trying to remove zombie cells entirely, the researchers focused on calming their harmful signals. According to senior author Dr. João Passos, this approach may offer wider benefits. Zombie cells tend to build up with age and contribute to many diseases, not just liver problems. Quieting their inflammatory signals early could help prevent damage before it becomes severe.
The research team believes that understanding these processes opens the door to new treatments. By targeting the pathways that cause zombie cells to trigger inflammation, doctors may one day slow or prevent the progression of MASH and other age-related diseases.
This could reduce the number of people who develop advanced liver disease and lower the need for liver transplants in the future.
The study also highlights the importance of basic cell biology in understanding human disease. A process meant to protect the body from viruses can, under certain conditions, turn against it. Aging cells that send the wrong danger signals can quietly cause long-term harm.
In reviewing these findings, the study offers strong evidence that zombie cells play an active and damaging role in MASH. It clearly shows how mitochondrial damage, immune sensors, and inflammation are connected. While the research was done in preclinical models, the results are convincing and provide a clear direction for future treatments.
More studies will be needed to confirm whether these findings apply fully to humans, but the mechanism identified is biologically sound and fits with what is already known about aging, inflammation, and liver disease.
Overall, this research adds an important piece to the puzzle of why fatty liver disease becomes so dangerous with age. It suggests that stopping harmful signals from aging cells may be just as important as treating fat buildup itself.
If future therapies can safely quiet these signals, they could change how doctors prevent and treat serious liver disease in aging populations.
If you care about liver health, please read studies that refined fiber is link to liver cancer, and the best and worst foods for liver health.
For more health information, please see recent studies about how to boost your liver naturally, and simple ways to detox your liver.
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