Results from a new study that appeared in the journal Nature Medicine raise some hope that certain drugs aimed at getting rid of senescent cells may promote healthier aging in some post-menopausal women.
The new work carried out by Mayo Clinic researchers shows that while these drugs may be useful to otherwise healthy post-menopausal women they are not necessarily effective universally.
According to scientists, senescent cells build up in the body as we get older. These are damaged cells that have become dormant. Often tagged “zombie cells”, they can no longer divide or work as they should but they remain in the body while posing a threat. These cells promote persistent inflammation and tissue dysfunction, which play major roles in chronic diseases and aging.
Recourse is usually to senolytic drugs to clear off these problematic cells from tissues. The new study suggests that older people with a lot of senescent cells are more likely to benefit from these drugs for healthier aging.
Research findings
Preclinical evidence suggests that the number of senescent cells increases in the body with age. Also, senolytic drugs were observed to help put off bone loss and a variety of age-related disorders.
The Mayo Clinic researchers tested a senolytic combination of dasatinib and quercetin in their 20-week, phase 2 randomized controlled trial. The study subjects were 60 healthy post-menopausal women who got the combination intermittently.
Dasatinib is an FDA-approved cancer drug. Quercetin is an increasingly popular compound for fighting aging, present in certain foods and also sold in supplement form.
The researchers found that the combination – which they called D+Q – enhanced bone formation but was not that effective for reducing bone resorption.
Bone resorption is the process by which bone tissues are broken down, thereby resulting in bone loss. It brings about a decline in both bone mass and bone density.
Results showed that the combination was, in particular, beneficial to people with the most senescent cells. These individuals showed notable growth in bone formation and reduced bone resorption. They also had better wrist bone mineral density.
Read Also: Dasatinib and Quercetin a Drug Cocktail That Could Prevent Back Pain in Old Age
This randomized controlled trial is the first to probe intermittent senolytic treatment in healthy older women, with bone metabolism employed as a treatment efficacy marker.
Increased bone formation was significant in the treatment group at both two and four weeks.
Exploring the potential of senolytic drugs
Many people are already using commercial senolytic products to promote healthy aging. Researchers, however, caution against such uses.
“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,” says Sundeep Khosla, M.D., senior study author and a Mayo Clinic endocrinologist. “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.”
People who age faster than normal look more likely to benefit from this type of treatment. Examples include cancer patients who got better after chemotherapy or people aged by certain disorders. Such people tend to have a high number of senescent cells.
Diabetes, heart disease, dementia, and idiopathic pulmonary fibrosis are among disorders that scientists think senolytics could also help with beyond aging.
There is a need for more research to better pinpoint people who might benefit from senolytics, Dr. Khosla noted. This will also help to develop or customize the drugs to make them more effective.
References
Farr, J.N., Atkinson, E.J., Achenbach, S.J. et al. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial. Nat Med (2024). https://doi.org/10.1038/s41591-024-03096-2
FEEDBACK:
