Senolytic therapy shows subtle impact on age-related bone health in women

An NIA-funded clinical trial investigating whether a senolytic drug combination could improve bone health in older women found just limited benefits compared to a control group. These findings, published in Nature Medicine, suggest that using senolytic products to reverse the effects of aging in humans has just a subtle effect despite earlier promising evidence from mouse studies. These mixed trial results for senolytics — drugs that clear out senescent cells — add to a growing body of research in this area, which remains a topic of scientific and public interest.

Each day, billions of damaged and worn-out cells in the body die and are replaced by new, healthy ones. However, as we age, some damaged cells stop dividing but do not die off; rather, they accumulate over time. Known as senescent cells, these lingering cells contribute to inflammation and possibly contribute to age-related declines, including issues such as metabolic dysfunction and reduced physical fitness. Senolytic drugs are designed to target and eliminate these cells to potentially mitigate such effects.

In this study, Mayo Clinic researchers conducted a Phase 2 randomized clinical trial involving 60 postmenopausal women ages 62-88 to assess senolytic effects on bone. Bone is continuously both formed and degraded as we age. When degradation rates exceed formation rates, bone loss occurs and can lead to osteoporosis. Participants were divided into two groups: One group of 30 women received a senolytic drug combination (dasatinib and quercetin) over 20 weeks, while a control group of 30 similar women did not receive the treatment. Researchers evaluated effects on factors influencing bone loss in both groups by measuring an indicator of rate of bone degradation (the primary outcome) and a marker of rate of bone formation (the secondary outcome). The results showed no difference between the groups in the marker of bone degradation. However, the women who took the senolytic drug mix had a higher level of the marker of bone formation at the trial’s early timepoints (two and four weeks), yet no difference compared to the control group by the 20-week mark.

These findings highlight both the potential and limitations of senolytic therapies. While promising, there is not yet clear evidence supporting their use for bone health or broader healthy aging goals. More research is needed to determine if the effects of senolytics depend on reducing underlying senescent cell burden and whether this can translate to meaningful clinical outcomes. In addition, since this study only included women, future research should also include men to better evaluate the safety and effectiveness of senolytics.

This research was funded in part by NIA grants R21AG065868, P01AG062413, R01AG076515, and R01AG055529.

Farr JN, et al. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: A phase 2 randomized controlled trial. Nature Medicine. 2024;30(9):2605-2612. doi:10.1038/s41591-024-03096-2.