Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of certain hematologic cancers. Researchers are now exploring whether this technology could also identify and eliminate senescent cells, which accumulate with age and may contribute to conditions such as diabetes, Alzheimer’s disease, and liver fibrosis.

In 2020, Spanish researcher Corina Amor Vegas, MD, PhD, a cellular biologist specializing in cancer and aging, assistant professor, and co-leader of the Cellular Communication in Cancer program at Cold Spring Harbor Laboratory’s Cancer Center in Cold Spring Harbor, New York, and colleagues published the first study showing that CAR T cells could be used as senolytic therapy.

The researchers identified the urokinase-type plasminogen activator receptor (uPAR) as a cell-surface protein whose expression increases in several types of senescent cells but is virtually absent from healthy tissues.

Researchers hypothesized that CAR T cells engineered to recognize and destroy cancer cells could also be programmed to target senescent cells. A study published in Nature found that CAR T cells targeting uPAR eliminated senescent cells in vitro and in vivo.

In animal models, the treatment reduced senescence-associated cells and improved abnormalities related to liver fibrosis, raising the possibility of using engineered cell therapy to target processes associated with aging.

Speaking with El Médico Interactivo on Univadis, part of the Medscape Professional Network, Amor Vegas discussed the use of CAR T-cell therapy to eliminate senescent cells.

How Senolytic CAR T Cells Work

Cellular senescence is not always detrimental. It can occur temporarily during processes such as tissue repair and help prevent damaged cells from proliferating during the aging process.

Problems can arise when senescent cells are not eliminated and accumulate in tissues, where they may promote chronic inflammation, disrupt stem cell function, and contribute to age-related deterioration. Senolytics are treatments designed to eliminate these cells.

Research on senolytic treatments has largely focused on drugs that exploit the vulnerabilities of senescent cells. CAR T-cell therapy offers a different approach: It uses immune cells modified to recognize and destroy cells carrying a specific target.

CAR T cells are T lymphocytes engineered to express an artificial surface receptor called the “chimeric antigen receptor.” This receptor directs cells toward a particular target, such as a molecule expressed by cancer cells. The aim of senolytic therapy is to identify a signal associated with senescent cells that can be used to target them.

A Single Dose With Effects Lasting More Than a Year

A major breakthrough came in 2024 when Amor Vegas and colleagues published further findings in Nature Aging regarding the ability of CAR T cells targeting uPAR to prevent and ameliorate age-related metabolic abnormalities in mice.

In one experiment, researchers administered a single dose of CAR T cells targeting uPAR to young mice and monitored them as they aged. In animals treated preventively, the therapy reduced age-related metabolic dysfunction and metabolic changes associated with a high-fat diet. It also reduced the number of cells expressing uPAR in tissues including the pancreas, liver, and adipose tissue. In older mice, the treatment improved glucose tolerance and exercise capacity.

One notable finding was the effect of the duration of CAR T-cell therapy. Senolytic CAR T cells persisted and expanded for more than 15 months in treated animals as they progressed from youth to old age. Laboratory mice typically live for approximately 2 years, which represents a substantial proportion of their lifespan.

This durability distinguishes CAR T cells from conventional senolytic drugs, which generally require repeated dosing. Cell therapies can persist in the body and respond when they encounter their targets.

“T cells have the ability to develop memory and persist in the body for very long periods, which is very different from a chemical drug. For chronic conditions, that’s a huge advantage,” Amor Vegas said.

A 2025 study, published in Nature Aging, extended this research to the aging intestine. In young and old mice, eliminating cells expressing uPAR improved intestinal barrier function, regenerative capacity, inflammation, and aspects of the mucosal immune response. Researchers also observed favorable changes in gut microbiome composition.

“In both cases, we have seen that they can absorb nutrients better and have much less inflammation. Furthermore, when irritated or injured, the epithelium regenerates and heals much faster,” she said. Researchers also observed these effects in human intestinal and colorectal cells, although these findings do not establish therapeutic efficacy in patients.

The Challenge: Identifying Which Cells to Eliminate

The goal is to program the immune system to recognize harmful senescent cells, eliminate them, and continue searching for harmful senescent cells if they reappear. However, cellular senescence is not a molecular state that is identical in all cells. No single type of senescent cell or universal marker can identify all senescent cells. This diversity is a major obstacle to the development of more precise senolytic treatments, including CAR T-cell therapies.

A study published in Molecular Cell in 2026, called SenCat, examined this problem in depth. The study was led by Carlos Anerillas, PhD, from the Fundación Agencia Aragonesa para la Investigación y el Desarrollo in Zaragoza, Spain.

The study involved the Severo Ochoa Molecular Biology Center, Spanish National Research Council in Madrid, Spain, and Aragon Health Sciences Institute in Zaragoza. Researchers analyzed the molecular profiles of 14 types of primary human cells subjected to more than 30 models of senescence. The findings showed that senescent cells share certain biological pathways but lack a universal marker that identifies them in every context.

Researchers also developed molecular signatures using machine learning to identify and quantify features of senescence across different human and mouse datasets. These tools may improve the identification of senescent cells; however, the findings also highlight a central challenge: CAR T cells must distinguish cells that need to be eliminated from those that need to be preserved.

uPAR Is Not the Only Potential Target

The uPAR protein is not a marker exclusive to senescent cells because it is involved in physiologic processes, including extracellular matrix remodeling and tissue repair, and may be expressed by certain immune cells. Lack of specificity is one of the main challenges that must be addressed before CAR T cells targeting uPAR can be considered for clinical use.

Therefore, research is focusing not only on enhancing CAR T-cell potency but also on improving specificity by identifying new targets that enable more precise recognition of distinct senescent cell populations.

One potential target is the family of NKG2D ligands, whose expression is increased in cells exposed to certain types of stress. A study published in Science Translational Medicine in 2023 developed CAR T cells that targeted these ligands. These cells eliminated human senescent cells in several experimental models. In aged mice, this approach improved several age-related abnormalities. Researchers also tested autologous CAR T cells in nonhuman primates, where treatment eliminated senescent cells without adverse effects.

Although these findings remain preclinical, they suggest another direction for future research. Rather than relying on a single protein associated with senescence, researchers may need to identify combinations of signals that can distinguish between specific populations of senescent cells. The central questions are which cells and tissues should be eliminated, at what point, and through which targets.

Safety Will Be Critical

Translating this strategy from the laboratory to clinical practice presents an important challenge: Aging is not the same as cancer. CAR T-cell therapy has shown substantial efficacy against certain hematologic cancers, but it can cause serious adverse effects, including cytokine release syndrome and neurologic toxicities. The balance between benefit and risk differs when treating a life-threatening disease vs targeting processes associated with aging, as discussed in a 2026 review published in Frontiers in Immunology.

Age-related changes in the immune system may also affect T-cell responses in older adults, raising questions about how autologous cell therapies should be manufactured and administered in this population. Other challenges include the complexity of manufacturing these treatments, monitoring how long the modified cells persist, and minimizing off-target effects.

Senolytic CAR T cells are still in the preclinical stage. No therapies of this type have been approved for the treatment of aging.

Research Moves Toward Neurodegenerative Disease

Amor Vegas’ research is now extending to another major area of age-related diseases: neurodegeneration. In March 2026, she received the MIND Prize from the Pershing Square Foundation, worth $750,000, to develop CAR T-cell therapies targeting neurodegenerative diseases, including Alzheimer’s disease.

The project aims to investigate how senescent cells outside the brain may contribute to neurodegeneration and to develop CAR T-cell therapies that could be safer and easier to scale.

The transition from animal models to clinical studies in patients could be a major step forward. However, researchers still need to determine whether engineered immune cells can distinguish harmful senescent cells from those that serve useful physiologic functions with sufficient precision. That distinction will be central to developing safe and effective senolytic therapies.

This article was translated from El Médico Interactivo on Univadis.