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UCLA Identifies Senescent Immune Cells Driving Fatty Liver, Reverses Damage in Mice

A new p21–TREM2 marker singles out dysfunctional macrophages for potential targeted senolytics.

Overview

  • UCLA researchers, whose Nature Aging study published Thursday, defined a p21–TREM2 signature that flags senescent, inflammation‑driving macrophages.
  • Using this marker, they found these cells rose from about 5% of liver macrophages in young mice to roughly 60–80% in old mice.
  • Lab tests showed high LDL cholesterol pushed healthy macrophages into this senescent state, linking overnutrition to accelerated cell aging.
  • Clearing the cells in mice with the senolytic ABT‑263 cut liver size from about 7% of body weight to 4–5% and reduced body weight by roughly 25% without diet changes.
  • Analysis of human liver biopsy data found the same signature enriched in diseased livers, prompting a search for safer macrophage‑targeting drugs than ABT‑263.