Drugs that target and eliminate senescent cells could be beneficial for older women who are otherwise healthy. However, Mayo Clinic researchers have determined that these drugs may not be a universal solution for everyone. Their research, published on July 2 in Nature Medicine, suggests that these drugs may only be effective for individuals with a high concentration of senescent cells.
Drugs that directly eliminate senescent cells may have positive effects on the health of older women but are not a one-size-fits-all remedy, caution Mayo Clinic researchers. Specifically, these drugs may only be advantageous for individuals with a significant number of senescent cells, according to a study published in Nature Medicine.
Senescent cells are dysfunctional cells in the body that become dormant. These cells, often referred to as “zombie cells,” are unable to divide but can trigger chronic inflammation and tissue dysfunction associated with aging and chronic illnesses. Senolytic drugs help to remove senescent cells from tissues.
In a 20-week phase 2 randomized controlled trial, 60 healthy postmenopausal women were intermittently administered a combination of senolytic drugs consisting of FDA-approved dasatinib and quercetin, a natural substance found in certain foods. This trial marked the first randomized controlled study of intermittent senolytic treatment in healthy aging women, with bone metabolism serving as an indicator of effectiveness.
The combination, known as D+Q, was found to enhance bone formation but did not decrease bone resorption or the breakdown of bone tissue. Notably, D+Q demonstrated the most benefits in individuals with high levels of senescent cells. This group exhibited more significant increases in bone formation, decreases in bone resorption, and an increase in bone mineral density at the wrist.
Dr. Sundeep Khosla, an endocrinologist at Mayo Clinic in Rochester, Minnesota, and senior author of the study, pointed out, “Our findings challenge the use of commercial products like quercetin or similar compounds like fisetin by individuals seeking anti-aging solutions without understanding whether they have a sufficient number of senescent cells to derive benefits, or the appropriate dosage and treatment schedule required to be effective yet safe.”
Dr. Khosla emphasized the need for further research to identify individuals who may respond well to senolytic treatments and to develop more specific and potent senolytic drugs that could benefit a broader population. Individuals who have undergone “accelerated aging,” such as cancer survivors following chemotherapy or those with progeroid syndromes, may have elevated levels of senescent cells.
In addition to their implications for aging, senolytic drugs could be beneficial in treating various diseases, including idiopathic pulmonary fibrosis, dementia, diabetes, heart disease, and others, Dr. Khosla noted. However, these drugs would likely need to be tailored based on their potency and the concentration of senescent cells in diseased tissues.
The study received support from several National Institutes of Health grants. Co-authors of the study include a team of researchers with diverse backgrounds and expertise, some of whom have financial interests tied to the research through Mayo Clinic patents and pending patents related to senolytic drugs and their applications, while the remaining authors have disclosed no competing interests.
