This Common Osteoporosis Drug Found to Significantly Slow Aging

Aging is a major risk factor for many diseases, including sarcopenia, cardiovascular disease, cognitive impairment, arthritis, respiratory disease, and osteoporosis.

While existing treatments can single-handedly reduce the symptoms of these diseases, the overall burden of these diseases is expected to increase significantly as the elderly population increases.

Zoledronic acid is a bisphosphonate commonly used in patients with osteoporosis or bone complications caused by multiple myeloma or cancer metastases with high safety and has been approved for clinical use for nearly 20 years.

An earlier meta-analysis showed that bisphosphonate use was associated with an overall reduction in all-cause mortality and cardiovascular mortality, but did not analyze the mechanism of action of zoledronic acid.

On May 7, 2023, Professor Sundeep Khosla’s team from the Department of Endocrinology at the Mayo Clinic In the US published a paper titled “In vitro and in vivo effects of zoledronic acid on senescence and in the journal Aging senescence-associated secretory phenotype markers. This study found that zoledronic acid has the effect of anti-aging and prolonging life through in vivo and in vitro experiments.

To determine the effect of zoledronic acid on cell senescence, researchers treated human lung fibroblasts (IMR90 cells) aged by etoposide with increased concentrations of zoledronic acid and found that zoledronic acid delayed cell senescence, but showed minimal cytotoxicity to non-senescent, proliferating IMR90 cells. The results showed that zoledronic acid had strong specificity for aging.

In addition, the anti-aging effect of zoledronic acid has an extremely high selectivity index (SI) of 93.3, which is the ratio of the maximum half effective killing concentration (EC50) value of non-senescent cells to senescent cells. In general, SI value ≥ 10 indicates that the compound is worthy of further study.

Based on these in vitro data, the researchers then evaluated whether zoledronic acid might reflect aging in mice through a reduction in circulating SASP protein. After 8 weeks of zoledronic acid treatment in 24-month-old mice, a significant decrease in circulating SASP factor and a significant increase in grip strength were observed in the experimental group compared with the control group.

Overall, in this study, a variety of complementary approaches were used to evaluate the possible effects of zoledronic acid on cell aging, and it was found that zoledronic acid has an anti-aging effect and that its beneficial extra-skeletal effects may be mediated at least in part by regulating cell aging.