Scientists are looking for answers to how to combat senescent cells, which can impair the performance of the brain and immune system, and the number of which increases with age.
The human body contains so-called zombie cells, which are called senescent cells. They no longer divide and perform their functions, but they do not die off and can harm their healthy “brethren.” Scientists believe that such cells slow down brain function and weaken the immune system, and their number, reports scientific journal Nature, increases with age.
Over the past decade, researchers have tried to eradicate them using various drugs. In 2015, scientists from the Mayo Clinic in the US found that a combination of two compounds – dasatinin and quercetin – destroyed these cells in old mice. The treatment made the animals less vulnerable, rejuvenated their hearts and increased their stamina. An important discovery gave rise to a new field of medicine called senolytics.
Additional impetus has come from recent results from animal studies and clinical trials in humans. Scientists are testing new and existing drugs that may have senolytic properties that help remove zombie cells from the body. They can help fight age-related diseases such as Alzheimer's disease and chronic lung and kidney diseases. Anirvan Ghosh, CEO of Unity Biotechnology, the company developing these drugs, says:
“I am confident that senolytics will have an impact in treatment. The only question is which drug will be the first approved.”
Scientists have created a drug called foselutoclax, which blocks the action of an anti-death protein in senescent cells. When they injected it into the eyes of diabetic mice, it destroyed the zombie cells but did not harm the healthy ones. The drug reduced the permeability of blood vessels in the retina of mice by 50%, and experimental animals began to cope better with vision tests.
The next step was a human trial. In the phase 2 study, researchers gave a single injection of the drug into the eyes of 30 people. After eleven months, those who received the drugs were able to read an average of 5.6 more letters on the eye chart compared to those who received the placebo. A few weeks later, one of the trial participants called Gaucher and said that the treatment had made his life much easier. Another noted a rapid improvement in color vision—the ability to perceive and differentiate between different colors. The team plans to publish the results later this year, but is conducting another test in the meantime.
Some scientists are using genetically modified immune CAR T cells. They can target and kill specific cells in the body and are approved to treat various types of cancer.
However, further research is needed to evaluate the safety of this therapy, said biologist Corina Amor of the Cold Spring Harbor Laboratory in New York. She says it would be nice to have a feedback lever for these cells to be able to regulate their influence and, if necessary, level it out if something goes wrong.
Other teams of researchers use gene therapy to destroy senescent cells. Scientists package the gene encoding the deadly protein into fat capsules coated with virus-derived proteins. They deliver the gene to cells in the lungs, hearts, livers, spleens and kidneys of mice and monkeys.
All of these approaches face challenges because there are many types of senescent cells. Researchers are just beginning to figure out how many there are and what their distinctive features are.
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