UCLA scientists have removed a harmful group of immune cells in mice and reversed fatty liver disease without changing the animals’ unhealthy diet.
How removing zombie cells repaired liver damage
The study, published in Nature Aging on April 16, 2026, identified senescent macrophages marked by the proteins p21 and TREM2 as drivers of chronic inflammation in aging and diseased livers. In young mice, only about 5% of liver macrophages showed this signature, but in older mice, the proportion rose to between 60 and 80%, closely matching increased inflammation. Clearing these cells reduced inflammation and reversed liver damage even while mice continued eating a high-cholesterol diet.
Why cholesterol accelerates cellular aging
Excess LDL cholesterol, not aging alone, can push healthy macrophages into a senescent state where they stop dividing but release inflammatory proteins. Ivan Salladay-Perez, first author and graduate student in the Covarrubias lab, explained that while macrophages normally handle cholesterol metabolism, chronic overload turns this process pathological. This mechanism links overnutrition directly to biological aging at the cellular level in fatty liver disease.
What the p21-TREM2 marker reveals
For years, researchers debated whether macrophages could become senescent because healthy versions share molecular features with dysfunctional ones. The UCLA team solved this by identifying the p21-TREM2 combination as a reliable signature of truly senescent macrophages that still drive tissue inflammation. Using this marker, they tracked how senescent macrophage accumulation increases with age and cholesterol exposure, providing a clear tool to distinguish harmful cells from normal immune activity.
What this means for future treatments
The findings suggest that selectively clearing senescent macrophages could become a new therapeutic strategy for fatty liver disease, which affects an estimated 30-40% of Los Angeles residents according to related UCLA research. Since liver damage reversed in mice without dietary changes, targeting these cells may help patients who struggle to maintain strict diets. However, the researchers caution that results in mice do not guarantee similar outcomes in humans, and clinical applications remain under investigation.
How did researchers identify senescent macrophages?
They used the combination of p21 and TREM2 proteins as a molecular signature to mark macrophages that are truly senescent and dysfunctional while still driving inflammation.
Can this treatment work without diet changes?
Yes, in mice, clearing senescent macrophages reversed liver damage and reduced inflammation even while the animals remained on an unhealthy, high-cholesterol diet.
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