Senolytics may be the key to a cure-all anti-aging pill

Intensifying anti-aging research in the field of senolytics is unlocking potential treatments that could help treat a wide range of age-related diseases. While getting old is generally considered to be a blessing, it also means fighting a war you’ll never win. Our bodies slow down as we age, exposing us to multiple chronic diseases. Research to understand the complex causes of these diseases has been the focus of scientists for decades. And while much progress has been made, there’s still a long way to go before definitive cures are developed to address the root cause of this deterioration. In an attempt to better solve the maladies of aging, researchers have explored what happens to the body’s cells when they are damaged. When cells are damaged beyond repair, they enter a protective state known as cellular senescence. This is a state in which a cell loses its power to divide and grow. The body responds by automatically engaging a self-destructing process known as apoptosis to prevent damaged or cancerous cells from spreading or containing damage within our bodies. However, in some cases, damaged cells may resist apoptosis and begin to leach out a harmful blend of proteins and compounds that cause inflammation and harm the cells around them. Researchers have found that as we grow older, the number of senescent cells will continue to build up, something that has been linked to conditions ranging from diabetes and arthritis to cardiovascular diseases. “It’s very hard to kill [senescent cells]. If you grow them under conditions that would kill a normal cell … they’ll survive and sometimes survive for years under those conditions,” said Dr. James Kirkland, a Mayo Clinic researcher who specializes in cellular senescence. Past studies have demonstrated that eliminating senescent cells might help alleviate some of the diseases of aging. Dr. Kirkland began research on the removal of senescent cells as far back as 2004. 11 years later in 2015, his team published a paper in the journal Aging Cell proving that two existing drugs could help to selectively remove senescent cells from human tissue. These two compounds – dasatinib and quercetin – were referred to as ‘senolytics’. Dasatinib is approved by the FDA for the treatment of cancer, while quercetin is a plant pigment that is naturally found in many fruits and vegetables. Dr. Kirkland’s team found that each one of these compounds targeted multiple cellular pathways that kept senescent cells alive. The researchers found that combining both of these compounds was effective in killing senescent cells. “We found there were senescent cells that wouldn’t respond to dasatinib or quercetin, but when we combined the two, we would kill them,” asserted Dr. Kirkland. A mice study conducted in 2017 examined the impact of these two senolytics on idiopathic pulmonary fibrosis (a fatal disease that is characterized by lung scarring). Mice that received a blend of dasatinib and quercetin showed a significant improvement, indicating that removing senescent cells could be used as a viable treatment. These findings were so promising that Kirkland started clinical trials using a small group of diabetic kidney patients in 2019. The researchers found that administering both senolytics for three days reduced the number of senescent cells in the patients’ bodies. The team is now conducting further research to prove how the compounds work, a key step towards securing FDA approval. Separate studies have supported Dr. Kirkland’s work on the removal of senescent cells. A 2015 paper published in Nature showed that another compound – navitoclax – was effective in removing senescent cells from mice that had been exposed to high levels of radiation. Navitoclax also helped replenish stem cells that had gone senescent. “Not only do you get rid of the bad cells, you also promote healthy stem cell expansion to regenerate normal cell tissues. So that’s almost like the fountain of youth … you may be able to rejuvenate your aged stem cells … and they can generate normal healthy cells to repopulate the tissues,” said Dr. Daohong Zhou, a study author, and professor at the University of Florida’s College of Pharmacy. Numerous other studies are examining senolytics for the treatment of conditions as varied as osteoporosis, Alzheimer’s, and macular degeneration. Scientists ultimately hope that as more breakthroughs are made, it may be possible to develop a cure-all pill that can tackle the ills of aging. But Dr. Kirkland cautions that such a treatment may still be years away from FDA approval. More research and larger clinical trials are needed to prove that these compounds work, as well as ascertain their safety. Kirkland is haunted by the possibility of dangerous side effects, “I think anything that sounds too good to be true probably is. I think we’re going to find side effects along the way, but I don’t know what they are.” Dr. John Morley, a geriatrician based at St. Louis University, also believes that more work is due before senolytic treatments can come to fruition. “You really need to study people over a huge amount of time to know whether the drugs work, if they work in everybody, and whether they have side effects on some people and not in others,” he says.