Scientists Discover Potential Liver Disease Treatment Through Removal of "Zombie" Cells

A hidden army of "zombie" immune cells may be quietly accelerating aging and fatty liver disease inside the body, according to striking new research from UCLA. Scientists found that removing these dysfunctional cells in mice dramatically reversed liver damage, even while the animals continued eating an unhealthy, high-fat diet.

The study, published in Nature Aging, focused on senescent cells, often nicknamed “zombie cells.” These are damaged cells that stop dividing but refuse to die. Instead, they remain trapped in tissues, releasing inflammatory chemicals that harm nearby cells and fuel chronic disease.

Researchers discovered that a specific type of immune cell called macrophages can become senescent with age and metabolic stress. Macrophages normally help clean up waste and defend tissues, but once they enter this dysfunctional state, they appear to drive persistent inflammation.

The UCLA team identified two proteins, p21 and TREM2, that together act as a clear signature for these harmful macrophages. In young mice, only about 5% of liver macrophages showed this senescent pattern. In older mice, however, the number jumped to as high as 80%, matching the rise in age-related liver inflammation.

Scientists also found that excess LDL cholesterol can trigger the process. When healthy macrophages were exposed to high cholesterol levels in the lab, they stopped functioning normally and began producing inflammatory signals linked to tissue damage.

To test whether removing these cells could reverse disease, researchers treated mice with a drug called ABT-263, which selectively destroys senescent cells. The results were dramatic. Fatty, enlarged livers shrank back toward healthy size, inflammation dropped sharply, and body weight fell significantly — all without changing the animals’ unhealthy diet.

Researchers then examined human liver biopsy data and found the same senescent macrophage signature strongly elevated in people with fatty liver disease, suggesting the mechanism may also occur in humans.

Although the drug used in the study is currently too toxic for routine human use, researchers are now searching for safer therapies that can specifically target and remove these harmful “zombie” cells before they trigger widespread tissue damage.

REFERENCE: Ivan A. Salladay-Perez; p21 TREM2 senescent macrophages fuel inflammaging and metabolic dysfunction-associated steatotic liver disease. Nature Aging, 2026; DOI: 10.1038/s43587-026-01101-6