Cold Spring Harbor Laboratory
Many people notice that certain foods become harder to tolerate with age. One possible reason is damage to the intestinal epithelium, a thin, single layer of cells that lines the intestine. This lining is essential for digestion and overall gut health. In healthy conditions, the intestinal epithelium renews itself every three to five days. Aging or exposure to cancer radiation can disrupt this renewal process, slowing or stopping regeneration altogether. When that happens, inflammation can rise and conditions such as leaky gut syndrome may develop.
Scientists at Cold Spring Harbor Laboratory (CSHL) have now identified a promising way to jump-start intestinal repair. Their strategy relies on CAR T-cell therapy, a powerful form of immunotherapy best known for treating certain cancers. By applying this approach to the gut, the researchers hope to open the door to future clinical trials aimed at improving intestinal health, particularly in people affected by age-related decline.
Targeting Aging Cells That Refuse to Die
This work builds on earlier research led by CSHL Assistant Professor Corina Amor Vegas, whose laboratory studies cellular senescence. As the body ages, it accumulates senescent cells, which no longer divide but also do not die off. These lingering cells have been linked to many age-related conditions, including diabetes and dementia. In earlier studies, Amor Vegas and her team engineered immune cells known as anti-uPAR CAR T cells that selectively remove senescent cells in mice, leading to major improvements in the animals’ metabolism.
The researchers next asked whether removing senescent cells could help restore the intestine’s ability to heal. Amor Vegas partnered with CSHL Assistant Professor Semir Beyaz and graduate student Onur Eskiocak to investigate. They delivered CAR T cells directly to the intestines of both younger and older mice. According to Amor Vegas, the results were striking. “In both cases, we see really significant improvements,” she says. “They’re able to absorb nutrients better. They have much less inflammation. When irritated or injured, their epithelial lining is able to regenerate and heal much faster.”
Protection Against Radiation-Induced Gut Damage
Leaky gut syndrome is particularly common among cancer patients who receive pelvic or abdominal radiation therapy. To model this, the team exposed mice to radiation that damaged their intestinal epithelial cells. Mice treated with CAR T cells recovered far more effectively than those that did not receive the therapy. Notably, a single dose of CAR T-cell treatment continued to support healthier gut function for at least one year.
The researchers also found compelling evidence that anti-uPAR CAR T cells encourage regeneration in human intestinal and colorectal cells, Eskiocak notes. While the precise biological mechanisms behind this effect are still being explored, the findings point to strong therapeutic potential. Beyaz emphasizes the broader significance of the work. “This is one good step toward a long journey in understanding how we can better heal the elderly,” he said.
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