International Business Department           Liu Bojia           January 29, 2023

  Speaking of CAR-T cells (antigen chimeric receptor T cells), many readers know that this cell therapy has shown extraordinary strength in the field of cancer treatment, especially for blood cancers.In October 2017, the world's first CAR-T therapy was approved by the FDA in the U.S., and it was the first to benefit patients with acute lymphoblastic leukemia.In 2021, CAR-T therapy was also approved for marketing in China , for the treatment of large B-cell lymphoma.

  However, to some scientists, the medical potential of CAR-T cells goes far beyond fighting cancer. Professor Corina Amor Vegas and colleagues at Cold Spring Harbor Laboratory (CSHL) have recently found a way to reprogramme T-cells in a way that allows CAR-T cells to fight aging. Their new proof-of-concept experiments, published in Nature Aging, a subseries of Nature, show that, with a single injection, these CAR-T cells can provide long-term benefits, helping to slow down aging in young mice or rejuvenate older mice to reduce "age-related diseases".

  Similar to the cancer-treating CAR-T cells, the anti-aging CAR-T cells in the new study were modified to target and eliminate specific cells, except that whereas the cancer-fighting CAR-T cells allow the T cells to identify and kill tumour cells, the anti-aging CAR-T cells identify and destroy senescent cells.

  Senescent cells are cells that have reached the limit of proliferation after dividing over and over again, but have not died, and are figuratively called "zombie cells". As the body accumulates senescent cells with age, they secrete and produce a range of pro-inflammatory factors that induce excessive inflammation, leading to a range of age-related tissue lesions.

  Effective removal of senescent cells, therefore, is seen as a promising anti-aging strategy and has been demonstrated in several animal experiments. In this new study, scientists gave CAR-T cells a new knack for targeting senescent cells and removing them.

  To do this, they "navigated" the T cells by reprogramming them to target a receptor on the surface of senescent cells, uPAR (urokinase-type fibrinogen agonist receptor). Experimentally, it was shown that uPAR-positive senescent cells increased with age in several tissues during the ageing process.

  In preclinical trials, this new strategy for removing senescent cells helped to rejuvenate older mice to a certain extent, not only improving age-related metabolic dysfunctions such as impaired glucose tolerance and liver metabolic deficiencies, but also significantly increasing the exercise capacity of the older mice after a period of treatment.

  The researchers further tested the long-lasting effects of anti-aging CAR-T cells on young mice. 3-month-old young mice received a single dose of anti-uPAR CAR-T cells, and uPAR CAR-T cells were detected to persist and expand throughout their lives. And from several metabolic and physical performance indicators, this preventive administration brought about a delayed aging effect in young mice, and also prevented the early development of metabolic dysfunctions that accelerate aging, such as obesity and diabetes, in young mice on a high-fat diet.

  The paper points out that most of the current anti-aging therapies targeting senescent cells focus on small molecule drugs (senolytics), which usually require multiple doses over time; in contrast, the new CAR-T cells, as a kind of "living" drug, can continue to exert their effects for many years with a single dose, and even have a lifelong impact, preventing common age-related diseases.

  The team says they are continuing to test the life-extending effects of the anti-aging CAR-T cells to see if they can keep mice healthy and alive for a long time. We'll see.