Imagine if your gut could heal itself-even after years of wear and tear. Scientists at Cold Spring Harbor Laboratory (CSHL) have discovered a way to help aging intestines do just that using a powerful immune technology originally developed for cancer treatment. The study, published in Nature Aging, found that CAR T-cell therapy can rejuvenate damaged intestinal tissue, reduce inflammation, and boost nutrient absorption in mice. Even more impressively, a single dose protected against radiation-induced damage and maintained gut health for up to a year.
As we age, our intestines lose their ability to repair themselves efficiently. The intestinal lining, or epithelium—a single layer of cells responsible for digestion and nutrient absorption—normally renews every few days. But with time or exposure to cancer treatments like radiation, this renewal process slows down, leading to inflammation and conditions such as “leaky gut.” The CSHL team set out to reverse that decline by targeting one of its underlying causes: senescent cells. These are aged cells that stop dividing yet refuse to die, releasing inflammatory molecules that damage surrounding tissue.
Amor Vegas and her team used a specially engineered form of immunotherapy known as anti-uPAR CAR T-cell therapy. Originally designed to fight senescent cells in metabolic diseases, these modified T cells were delivered directly into the guts of both young and old mice. The results were striking—treated animals showed faster healing of intestinal injuries, healthier epithelial linings, less inflammation, and improved nutrient uptake.
To test whether the therapy could protect against extreme damage, the team exposed mice to gut-harming radiation like that used in cancer therapy. Those given CAR T-cell treatment recovered dramatically better than untreated mice. Further experiments on human intestinal and colorectal cells produced similar results, suggesting strong potential for translation to clinical applications.
The findings hint at a future where CAR T-cell therapy could do more than fight cancer—it could also rejuvenate the body from the inside out, restoring one of its most vital organs.
REFERENCE: Onur Eskiocak, Joseph Gewolb, Vyom Shah, James A. Rouse, Saria Chowdhury, Erdogan O. Akyildiz, Inés Fernández-Maestre, Jacob A. Boyer, Aveline Filliol, Alexander S. Harris, Raditya Utama, Guangran Guo, Carolina Castro-Hernández, Emmanuella Nnuji-John, Charlie Chung, Arianna Anderson, Sara Flowers, Jill Habel, Paul B. Romesser, Ross L. Levine, Scott W. Lowe, Michel Sadelain, Semir Beyaz, Corina Amor. Anti-uPAR CAR T cells reverse and prevent aging-associated defects in intestinal regeneration and fitness. Nature Aging, 2025; DOI: 10.1038/s43587-025-01022-w
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