Mayo Clinic researchers have found that drugs targeting “zombie” cells in otherwise healthy older women may benefit health.
Zombie cells, also known as senescent cells, are cells that malfunction because of age. They are called zombie cells because they have slipped into a dormant stage: They’re not dead, but not really alive, either. What’s more, they can’t divide or reproduce as do normal cells. Instead, these cells drive inflammation and tissue dysfunction linked to aging and chronic diseases, including Alzheimer’s, arthritis, and certain cancers.
However, a new study published in Nature Medicine found that senolytic drugs can help clear tissues of these senescent cells.
Women With More Zombie Cells Benefited Most
In a 20-week trial, researchers intermittently gave 60 healthy, postmenopausal women a combination of senolytic drugs: dasatinib, an anti-cancer medication approved by the U.S. Food and Drug Administration (FDA) shown to target zombie cells, and quercetin, a chemical from plants (such as onion) that has antioxidizing and anti-inflammatory properties.
Other animal studies have shown that the combination of dasatinib and quercetin kills zombie cells.
The research team found that the combination, called D+Q, benefited the women’s bone formation but did not reduce bone breakdown or removal of bone tissue. In addition, women with the highest senescent cell level benefited the most from D+Q. These women showed the most significant improvements in bone formation, decreases in bone resorption, and increases in bone mineral density at the wrist.
The positive response to D+Q regarding bone metabolism seemed to differ individually, with those with the highest senescent cell load benefiting the most, the authors wrote.
While most women showed only a temporary improvement in bone metabolism at Week 2, women with the highest senescent cell load continued to have higher bone metabolism activity at Week 20. Some improvements, such as decreased bone resorption, remained temporary. For instance, by Week 2, bone breakdown returned to baseline levels.
The authors, therefore, argued that the drug combination may be helpful only to women who have the highest senescent load and that their study may not have included enough numbers of such women.
“Our findings argue against what many people are already doing—using commercial products like quercetin or related compounds like fisetin that may show some senolytic properties,” Dr. Sundeep Khosla, an endocrinologist at the Mayo Clinic and senior author of the study, said in a statement. “They’re using them as anti-aging agents without knowing if they have high enough senescent cell numbers to benefit, or what dose or dosing regimen is needed to be effective yet safe.”
Clinical trials are underway on the effect of senolytic drugs on numerous diseases, such as diabetes, Alzheimer’s, and COVID-19.
Cocktails such as D+Q can come with adverse effects. For example, in the Mayo Clinic study, potential side effects included headache, experienced by 53 percent of participants; diarrhea, 23 percent; nausea, 17 percent; body pain, 17 percent; fatigue, 13 percent; and constipation, 10 percent.
Are Senescent Cells All Bad?
While anti-aging medications such as senolytic drugs are a hot trend, some researchers wonder if they’re necessary.
Research has shown that some senescent cells are beneficial and shouldn’t be killed off. A 2022 University of California (UC)–San Francisco study found that some senescent cells can actually heal. The researchers found that more senescent cells exist in young and healthy tissues than previously thought and that, as they form, they secrete a growth hormone that stimulates stem cells to grow and repair tissues.
“The studies suggest that senolytics research should focus on recognizing and precisely targeting harmful senescent cells, perhaps at the earliest signs of disease, while leaving helpful ones intact,” Leanne Jones, director of the UC San Francisco Bakar Aging Research Institute, said in a 2022 statement. “These findings emphasize the need to develop better drugs and small molecules that will target specific subsets of senescent cells that are implicated in disease rather than in regeneration.”
In the statement, Dr. Khosla said that senolytic drugs could be helpful against certain diseases and noted that they may help patients with idiopathic pulmonary fibrosis, dementia, diabetes, and heart disease. However, the drugs must be customized according to the potency and amounts of senescent cells in the diseased tissues, he said.