A Cold Spring Harbor Laboratory study demonstrated CAR T-cell therapy can reverse age-related intestinal decline in mice by targeting senescent cells. While promising, experts caution on safety risks, off-target effects, dosing, and costs for human use.
Cold Spring Harbor Laboratory researchers, led by Semir Beyaz and Corina Amor, engineered CAR T-cells to target uPAR—a marker of senescent cells accumulating with age. In older mice, the therapy restored youthful stem cell-driven renewal of the gut lining (which turns over every 3-5 days), improved barrier integrity, and reduced inflammation, as detailed in initial reports.
"We didn’t just stop the ageing process, but also observed a reversal," said Amor. Beyaz noted: "The decline... is a deficit in the fitness of the stem cells," which the therapy addressed.
Experts praise the potential to mitigate age-related gut issues like infections, damage, and cancer risk (Tuomas Tammela, Memorial Sloan Kettering). However, challenges loom: uPAR appears on some healthy tissues, risking unintended effects elsewhere (Jesse Poganik, Harvard Medical School). Safety, dosing, and human efficacy remain unproven. The therapy's complexity and cost make routine use unlikely soon (Joana Neves, King’s College London).
With no existing treatments for faltering gut regeneration, this advances anti-aging research. Full study: Nature Aging (DOI: 10.1038/s43587-025-01022-w).
