UCLA p21+TREM2 Senolytic Macrophage Study (Salladay-Perez & Covarrubias 2026)
A 2026 UCLA paper in Nature Aging identified p21+TREM2 as a dual marker for senescent liver macrophages and showed that clearing these cells with {{ABT-263}} reversed fatty-liver phenotype in mice on a continued high-fat, high-cholesterol diet. The finding is a target-validation advance, not a near-term human therapy, because the drug is too toxic for human use and treated mice also lost 25% body weight.
Salladay-Perez, Covarrubias et al. (Nature Aging, April 2026) reported that p21+TREM2+ macrophages accumulate in aging and diseased livers and drive inflammaging and MASLD. The dual-marker signature distinguishes genuinely dysfunctional, persistently inflammatory macrophages from healthy ones that transiently express either marker alone. The p21+TREM2+ fraction of liver macrophages rises from roughly 5% in young mice to 60-80% in old mice and is elevated in human liver biopsy datasets from diseased versus healthy livers. Exposing healthy macrophages to high LDL cholesterol in vitro induced the same phenotype, including secretion of the SASP (senescence-associated secretory phenotype) cytokine program. This frames cholesterol as an active senescence inducer in immune cells rather than a passive lipid deposit. In the intervention arm, mice on a high-fat, high-cholesterol diet were treated with the senolytic ABT-263 (navitoclax), a Bcl-xL inhibitor that selectively triggers apoptosis in senescent cells. Liver weight fell from about 7% of body weight to a healthy 4-5%, livers became visibly smaller and a healthier color, and the fatty-liver phenotype reversed even though the diet was held constant. Body weight also dropped from roughly 40g to 30g, a 25% reduction the press materials did not disentangle from the drug's direct hepatic effect. The press release made no claim about fibrosis reversal, the step in MASH progression that actually drives mortality. The novelty is the p21+TREM2 biomarker, not the senolytic strategy, which has been published in the MASLD context since Ogrodnik et al. 2017. UCLA explicitly notes a follow-on drug-screening program to find safer compounds; the translational lift has not yet started.