"This is one of the most exciting fields in all of medicine or science at the moment," said Dr. James Kirkland, director of the Kogod Center on Aging at the Mayo Clinic and lead author of the new paper.
Senescent cells play a role in many age-related chronic diseases, such as diabetes, cardiovascular disease, most cancers, dementia, arthritis, osteoporosis and blindness, Kirkland said. Therefore, senolytic drugs are a possible treatment approach for such diseases.
As a practicing physician, Kirkland said that he has grown increasingly concerned for his patients who are sick with many of these age-related conditions.
"The same processes that cause aging seem to be the root causes of age-related diseases," he said. "Why not target the root cause of all of these things? That would have been a pipe dream until a few years back."
Fourteen senolytic drugs have been discovered and are being actively studied, 11 of which Kirkland's colleagues and their collaborators found, he said.
Are these age-modifying drugs ready for human trials?
Scientists have long known that certain processes influence your body's aging on the cellular level, according to the paper. Those processes include inflammation, changes in your DNA, cell damage or dysfunction and the accumulation of senescent cells.
It turns out that those processes are linked. For instance, DNA damage causes increased senescent cell accumulation, Kirkland said.
So an intervention that targets senescent cells could attenuate other aging processes as well, according to the new paper. That is, once such an intervention is tested for efficacy and safety.
"I think senolytic drugs have a great future. If it is proven that it can reduce senescent cells and rejuvenate tissues or organs, it may be one of our potential best treatments for age-related diseases," said Dr. Kang Zhang, founding director of the Institute for Genomic Medicine at the University of California, San Diego, who was not involved in the new paper.
Yet taking senolytic drugs from mouse studies to human ones is a "big leap," Zhang said.
"So we will have to wait for clinical trials to see whether this would work in humans," he said. "One possible clinical trial strategy is to test this class of drugs in an age-related disease, such as neurodegeneration, like Parkinson's disease, to see if it can reduce clinical severity of the disease and improve tissue functions."
In the new paper, the researchers wrote that potential clinical trial scenarios include testing whether senolytic drugs could alleviate multiple chronic diseases in a single patient or whether such drugs could treat conditions that involve senescent cell accumulation in one location in the body, such as osteoarthritis.
Other potential clinical trial scenarios include testing whether the drugs could alleviate frailty in older adults or could treat conditions associated with chemotherapy or radiotherapy, since radiation can produce cellular senescence, Kirkland said.
For instance, "in mice, if you treat one leg with enough radiation, after three months, the mouse has trouble walking. If you give a single dose of these drugs, they're able to walk quite well, and that persists for two years," he said. "These drugs could mitigate the effects of therapeutic radiation."
"Some of the drugs at the moment are moderately expensive," he said.
"If we're able to reduce hospitalizations ... the savings on the medical care and hospital side might more than offset the cost of these drugs by a longshot," Kirkland said, though it remains unclear what the dosage options would be for senolytic drugs for short- or long-term use.
As for how soon he thinks human clinical trials might commence, Kirkland said doctors could have an idea of how well senolytic drugs work for serious health conditions in about a year and a half or two years.
Once the drugs are tested in humans, researchers expect many companies to be lining up to develop or manufacture senolytic drugs. Some have already expressed interest.
"In the coming decades, I believe that health care will be transformed by this class of medicine and a whole set of diseases that your parents and grandparents have will be things you only see in movies or read in books, things like age-associated arthritis," said David, whose company was not involved in the new paper.
Yet he cautioned that, while many more studies may be on the horizon for senolytic drugs, some might not be successful.
"One thing that people tend to do is, they tend to overestimate things in the short run but then underestimate things in the long run, and I think that, like many fields, this suffers from that as well," David said.
"It will take a while," he said. "I think it's important to recognize that a drug discovery is among the most important of all human activities ... but it takes time, and there must be a recognition of that, and it takes patience."
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