Sirolimus Use In Allogeneic Hematopoietic Cell Transplant Recipients: Assessing Its Senotherapeutic Role In A High Risk Population
Undergoing a blood stem cell transplant, a vital treatment for various blood cancers and disorders, can unfortunately accelerate the aging process in patients. This happens because the intense treatments involved can lead to an accumulation of “senescent cells”—cells that have stopped dividing and can release harmful substances, contributing to inflammation and tissue damage, a process sometimes called “inflammaging.”
A medication called rapamycin (also known as sirolimus) has shown promise in slowing down aging and clearing these senescent cells in various studies, particularly when administered at lower doses. Interestingly, this same medication is routinely used at higher doses in transplant patients to prevent a serious complication called Graft-versus-Host Disease, where the donated cells attack the recipient’s body.
Researchers wondered if the doses of rapamycin already being used to prevent transplant complications might also offer a “senotherapeutic” or anti-aging benefit to these high-risk patients. They compared patients receiving rapamycin-based treatment to those on another standard regimen, looking for changes in markers of cellular aging over time.
However, the study found that at the doses typically used to prevent transplant complications, there was no statistically significant reduction in these markers of senescent cells. While a slight, non-significant trend towards lower aging markers was observed in the rapamycin group, the findings suggest that the specific daily dosing used for preventing transplant complications may not be sufficient to provide the anti-aging benefits seen with different dosing strategies. This highlights that the anti-aging effects of rapamycin might depend on a specific “therapeutic window”—perhaps lower or intermittent doses—different from what’s currently used in transplant care. This research underscores the need for continued investigation into how best to integrate anti-aging strategies for individuals undergoing life-saving transplants.