The T Guardian Cells: Armies for a Timeless Body

Cellular senescence is a stress response program that is distinguished by sustained cell cycle arrest and the formation of the senescence-associated secretory phenotype (SASP), which contains pro-inflammatory cytokines and matrix remodeling enzymes. In physiological settings in young people (for example, wound healing, tumor suppression), the SASP helps to the recruitment of immune cells, whose job is to clear senescent cells and enable the restoration of tissue homeostasis.

Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs called senolytics may eliminate senescent cells, they require continuous administration. 

With adequate genetic alterations, these white blood cells may target senescent cells. While various medications are already available to remove these cells, many must be taken frequently over time. Researchers found that a "living" medication known as CAR (chimeric antigen receptor) T cells could possibly be programmed to remove senescent cells in mice. (CAR) T cells target the urokinase plasminogen activator receptor (uPAR), a molecule associated with senescence. The uPAR-positive senescent cells accumulate with age and can be safely targeted with senolytic CAR T cells. Treatment with anti-uPAR CAR T cells enhances exercise capacity in physiological aging and alleviates metabolic dysfunction. 

Importantly, as T cells unlike chemical drugs, can establish memory and stay in your body for extended periods of time, a single dose of these senolytic CAR T cells is enough to have long-term therapeutic and preventative effects. CAR T cells have been utilized to treat a variety of blood malignancies, and the FDA approved its usage in 2017. However, new discoveries indicate that the medical promise of CAR T cells extends beyond cancer.

REFERENCES:

Amor C, Fernández-Maestre I, Chowdhury S, Ho YJ, Nadella S, Graham C, Carrasco SE, Nnuji-John E, Feucht J, Hinterleitner C, Barthet VJ. Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nature Aging. 2024 Jan 24:1-4.

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