Back in 2015 we saw a new class of drugs emerge with huge potential when it comes to the aging process and how it might be slowed. Scientists working to improve the potency and safety of these so-called senolytic drugs have made a significant discovery, pioneering an antibody treatment that closes in on the target cells with a new level of precision, while leaving healthy cells unharmed.
The massive potential of senolytics lies in their ability to take aim at what are known as senescent cells. These are cells that have lost their ability to divide and instead accumulate in the body and accelerate the aging process. While this is a natural part of growing older, scientists have made some exciting inroads around how these cells can be cleared from the body with purpose-made drugs.
Senolytic drugs have been shown to rejuvenate old cells in rodents and also increase their lifespan, while promising advances have also been made in using them to improve healthspan, or the amount of our lives we spend healthy. Just last month we looked at an exciting example of this, in which scientists demonstrated how senolytic drugs can remove senescent cells in aging rodent spines and create space for healthy new cells to flourish, raising the prospect of new treatment for chronic back pain in humans.
The international team of scientists behind this latest study have taken aim at what they see as a shortcoming in the current generation of senolytic drugs. In their view, these drugs take something of a scattergun approach in need of refining.
“Senolytics are a new class of drugs with great potential to ameliorate aging," says the University of Leicester's Dr Salvador Macip, study author. “However, the ones we have found so far are quite unspecific and thus may have strong side effects. That is why there is much interest in a second generation of drugs, the targeted senolytics, which should eliminate senescent cells without affecting the rest."
The breakthrough builds on earlier research from the team that identified a membrane marker of senescent cells, and showed how it could be targeted to eliminate them with a high level of precision. With this marker in their crosshairs, the scientists developed a novel compound consisting of an antibody loaded with drugs toxic to senescent cells, and put it to the test on cell cultures in the lab.
These proof-of-concept experiments returned some promising results, with the antibody-drug conjugate acting like a "smart bomb," recognizing the senescent cells and pumping them with the toxic drugs to take them out of the equation. The scientists confirmed that the treatment had no effect on non-senescent cells, boding well for the precision and safety of the treatment.
“Copying an idea already in use in cancer therapies, we tweaked an antibody so it could recognize these cells and deliver a toxic cargo specifically into them," says Macip.
The scientists describe this as an entirely new method for clearing senescent cells, and the first in vitro proof of its specificity and efficiency. They hope to one day replicate this success in humans, and will use these results as the basis for further study into more targeted treatments for senescence.
The research was published in the journal Scientific Reports.
Source: University of Leicester
