As the human body grows older, its tissues accumulate higher concentrations of what are known as senescent cells, which no longer possess the ability to divide and instead accelerate the aging process. By investigating this process in discs in the spine, scientists have shown how so-called senolytic drugs that removes these destructive cells can prevent age-related deterioration, raising the prospect of a new opioid-free treatment for back pain in humans.
Since their emergence in 2015, senolytic drugs that take aim at senescent cells have shown significant promise in anti-aging research efforts. We've seen how this relatively new class of drugs can increase the lifespan of mice, but a huge part of their promise lies in their potential to improve our healthspan, or the amount of our lives we spend healthy, with scientists also showing how they can be used to rejuvenate old cells in rodents and make them behave like young cells once again.
Age-related back pain is common condition and one in direct conflict with the idea of a lengthy healthspan, but through further experiments in rodents scientists have shown how senolytic drugs again could flip the script. Much of the chronic back pain afflicting adults is tied to the deterioration of spinal discs that offer support for the vertebrae, and while surgery and steroid injections can help, they aren't suitable for all and can have limited effectiveness. Opioid-based painkillers, meanwhile, are strong and effective but carry a risk of addiction.
Senescent cells do much of their damage by secreting harmful enzymes and inflammatory proteins that affect neighboring tissues, and by taking them out of the equation, senolytic drugs create space for healthy new cells to replace them and improve function of these tissues. While they have shown promise in a number of areas, the authors of the new study note there are no guarantees when it comes to how they will perform in new locations in the body.
“Just because the drugs work in one tissue doesn’t mean they will also work in another,” says study author Makarand Risbud, from Thomas Jefferson University. “Every tissue is different.”
The research team carried out experiments in which young, middle-aged and elderly mice were all given a weekly cocktail of senolytic drugs consisting of dasatinib and quercetin, two drugs that are currently the subject of clinical trials for treating scarred lung tissue. The treatment did indeed have an effect, but not in exactly the way the scientists had expected.
The researchers anticipated the drugs would have the most profound effect on the older animals with larger concentrations of senescent cells, but it was actually the younger animals that experienced the greatest benefit. These, along with the middle-aged mice, showed less disc degeneration and featured fewer senescent cells by the time they reached old age than a group of control mice given a placebo.
“We anticipated that in tissues with a lot of senescence, removing the senescent cells would make a big difference, but it didn’t,” Dr. Risbud says. “The therapy was most effective when we started treating the mice when those senescent cells were just beginning to emerge. Our findings show that if given early, senolytic drugs can actually slow disc degeneration. This is a novel preventive approach."
That the mice required weekly injections of the senolytic drugs from a young age is a clear downside to the approach in its current form, but importantly, the researchers report no adverse effects from this long-term treatment. By showing that they can mitigate the age-related degeneration of spinal discs, the study does lay a promising foundation for further investigations into how they might one day alleviate back pain in human sufferers.
“This research paves the way for translating these studies first to a preclinical animal model and then to a clinical trial in humans,” says Dr. Risbud says.
The research was published in the journal Nature Communications.
Source: Thomas Jefferson University
