Chimeric Antigen Receptors Target Senescent Cells, Can Be Reprogrammed to Slow Down and Reverse Aging

For ages, humans have searched for a way to stay young, inspiring explorers to look for the fountain of youth. As it turns out, the secret to resisting aging has been inside us all along.

Cellular Senescence

As we age, our bodies accumulate a whole host of damaged cells that have stopped multiplying but have not died off. They stay in the body and release chemicals that can trigger inflammation.

These cellular oddballs are called senescent cells and lead to a myriad of age-related diseases. As we age, a decreased immune system function, combined with increased tissue damage, accumulates senescent cells.

Scientists have been actively searching for the genes and other biological factors that make these cells resilient for many years. It even includes testing a class of drugs called senolytics developed to wipe them out. Existing drugs can eliminate these cells, but they must be taken repeatedly.

Fountain of Youth

In a new study, experts from Cold Spring Harbor Laboratory have found a way to reprogram chimeric antigen receptor (CAR) T cells to target the senescent cells. Their research results are discussed in the paper "Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction."

T cells have been known to play significant roles in the body's immune system. They can act as 'killer cells' which attack cells infected with a virus or other pathogens. They can also function as 'helper cells,' which support B cells in making antibodies.

Another feature of T cells is their ability to be engineered to fight cancer. In CAR T cell therapy, the T cells of a patient are modified in the laboratory to produce surface proteins. They use these proteins to recognize and bind to specific antigens on the surface of cancer cells, which they destroy afterward. If given the right set of genetic conditions, these white blood cells can attack another group of cells, such as senescent cells.

Senescent cells are found to carry the cell-surface protein urokinase plasminogen activator receptor (uPAR). Knowing this, the researchers first investigated the association between the protein and aged tissues.

Led by CSHL assistant professor Corina Amor Vegas, the scientists extracted T cells from mice and genetically engineered them to express a CAR on their surface. Using this process, they could remove senescent cells, which improved mice's health without harming their tissues. The animals also gained better metabolism, lower body weight, increased physical activity, and glucose tolerance. The process promotes rejuvenation in old mice and slows aging in younger ones.

According to the authors, a good thing about CAR T cells is their ability to have a long-lasting impact with only one treatment in early life. A single dose can successfully protect against health conditions like diabetes and obesity, which usually show up later in life.

Since 2017, CAR T cells have been approved by the US Food and Drug Authority (FDA) to treat blood cancers. Meanwhile, Amor Vegas is one of the first researchers to prove that the medical potential of CAR T cells goes even further than cancer.