Scientists have developed a novel way to target and eliminate senescent cells, which are old and dysfunctional cells that cause inflammation and contribute to ageing and many chronic diseases. The new method uses CAR-T cell technology, which is usually used for the treatment of cancer, to selectively kill senescent cells without harming healthy cells.
What are Senescent Cells and Why are They Harmful?
Senescence is a state of permanent cell cycle arrest that occurs when cells are damaged or stressed. Senescent cells stop dividing, but they do not die. Instead, they secrete various inflammatory factors, known as the senescence-associated secretory phenotype (SASP), that can damage nearby healthy cells and tissues. Senescent cells accumulate with age, as the immune system becomes less efficient at clearing them. They have been implicated in many age-related diseases, such as cancer, cardiovascular disease, osteoarthritis, stroke, and neurodegeneration.
How Does CAR-T Technology Work?
CAR-T technology is a form of immunotherapy that involves engineering T cells, which are a type of immune cell, to express a chimeric antigen receptor (CAR). The CAR is designed to recognize and bind to a specific antigen, which is a protein fragment that is present on the surface of a target cell. When the CAR-T cell binds to the antigen, it becomes activated and kills the target cell. CAR-T technology has been successfully used to treat some types of blood cancers, such as leukemia and lymphoma.
How Can CAR-T Technology Target Senescent Cells?
To use CAR-T technology to target senescent cells, the researchers had to identify an antigen that is specific to senescent cells and not expressed by healthy cells. They screened several candidates and found that the urokinase-type plasminogen activator receptor (uPAR) was highly expressed by senescent cells in both mice and humans. They then engineered CAR-T cells to recognize uPAR and tested their ability to kill senescent cells in vitro and in vivo.
What are the Benefits of Eliminating Senescent Cells?
The researchers found that their uPAR-targeted CAR-T cells were able to selectively kill senescent cells without affecting normal cells. They also showed that the CAR-T cells could reverse some of the pathological effects of senescence in mouse models of liver fibrosis, osteoarthritis, and neurodegeneration. The treatment improved liver function, reduced joint inflammation and pain, and enhanced cognitive performance in the mice. The researchers also observed no significant toxicity or adverse effects from the CAR-T therapy.
What are the Implications and Challenges of this Research?
The study demonstrates that CAR-T technology can be adapted to target senescent cells and potentially treat a range of age-related diseases. This could open new avenues for developing therapies that improve healthspan and lifespan. However, there are still some challenges and limitations that need to be addressed before this approach can be translated to humans. For example, the safety and efficacy of uPAR-targeted CAR-T cells need to be confirmed in larger and longer-term studies.
Moreover, the optimal dose, frequency, and timing of the treatment need to be determined. Furthermore, the possibility of off-target effects or immune reactions against the CAR-T cells need to be carefully monitored.
