New drug class prevents key ageing mechanism in organ transplants
A novel study has shown that Senolytics, a new class of drugs, have the potential to prevent the transfer of senescence, a key mechanism of ageing, in recipients of older donor organs.
The pioneering research, presented today at the European Society for Organ Transplantation (ESOT) Congress 2023, opens promising avenues for expanding the organ donor pool and enhancing patient outcomes.
By transplanting older donor organs into younger recipients, researchers from Harvard Medical School and the Mayo Clinic investigated the role of transplantation in inducing senescence, a biological mechanism linked to ageing and age-related diseases. The researchers conducted age-disparate heart transplants from both young (3 months) and old (18–21 months) mice into younger recipients. Recipients of old hearts showed augmented frequencies of senescent cells in draining lymph nodes, livers, and muscles, in addition to augmented systemic mt-DNA levels, compared to recipients that received young grafts. Strikingly, transplanting old organs led to advanced physical and cognitive impairments in recipients.
The research also uncovered a potential solution to this process by utilising Senolytics – a new class of drugs designed to target and eliminate senescent cells. When old donors were treated with Senolytics (Dasatinib and Quercetin) prior to organ procurement, the transfer of senescence was significantly reduced through a diminished accumulation of senescent cells and mt-DNA. Recipients who received old organs treated with Senolytics showed improved physical fitness that was comparable to observations in recipients of young organs.
Maximillian J. Roesel, presenting the study as part of the group at Brigham and Women’s Hospital, Harvard Medical School, commented, “Donor age plays a crucial role in transplant success, with recipients of older organs facing worse outcomes. Nevertheless, the use of older donor organs is essential to tackle the global organ shortage, and this research illuminates fundamental challenges and potential solutions for utilising older organs.”
“Moving forward, we will further investigate the potential role of Senolytics in preventing the transfer of senescence in humans. This research is extremely exciting as it may help us improve outcomes and also make more organs available for transplantation,” concluded Stefan G. Tullius, the lead author of the study.