Scientists at Cold Spring Harbor Laboratory have demonstrated that CAR T-cell therapy—best known for treating certain cancers—can rejuvenate aging intestines by selectively eliminating senescent cells. The research, published in Nature Aging, opens the door to future clinical trials aimed at improving gut health in elderly patients.
The study, led by Assistant Professors Corina Amor Vegas and Semir Beyaz, along with graduate student Onur Eskiocak, builds on earlier work showing that engineered immune cells can clear senescent cells—those that no longer divide but refuse to die and accumulate with age. These lingering cells have been linked to numerous age-related conditions, including diabetes, dementia, and chronic inflammation.
How It Works
The researchers used anti-uPAR CAR T cells, which are engineered to recognize and destroy cells displaying the uPAR protein—a marker commonly found on senescent cells. When delivered directly to the intestines of aged mice, these therapeutic cells selectively removed the accumulated senescent cells without harming healthy tissue.
The results were striking. Treated mice showed improved nutrient absorption, significantly reduced inflammation, and faster regeneration of the epithelial lining that protects the gut. Perhaps most remarkably, these benefits were sustained for at least one year after a single treatment dose—suggesting long-lasting therapeutic effects.
Protection Against Damage
Beyond rejuvenating aged intestines, the CAR T cells also protected against radiation-induced gut damage, a common and serious side effect of cancer treatment. The researchers additionally confirmed that the approach works in human intestinal and colorectal cells, suggesting translational potential.
"In both cases, we see really significant improvements. They are able to absorb nutrients better. They have much less inflammation," said Amor Vegas. Her colleague Beyaz added: "This is one good step toward a long journey in understanding how we can better heal the elderly."
Implications for Aging
The gut plays a central role in overall health, affecting everything from immune function to metabolism to even brain health via the gut-brain axis. Age-related decline in intestinal function contributes to malnutrition, weakened immunity, and increased frailty in older adults. A therapy that could reverse this decline would represent a significant advance in longevity medicine.
The CSHL team notes that while more research is needed before human trials, the success of CAR T therapy in other medical contexts provides a established framework for clinical development. The specificity of the anti-uPAR approach—targeting only senescent cells—may offer advantages over systemic senolytic drugs that affect the entire body.
