Senolytics, a new family of medications, have the potential to prevent the transmission of senescence, a crucial process of aging, and the accompanying physical and cognitive deficits in recipients of older donor organs, according to a recent study.
The groundbreaking discovery, which was presented at the European Society for Organ Transplantation (ESOT) Congress 2023, opens up intriguing paths for increasing the pool of organ donors and improving patient outcomes.
Researchers from Harvard Medical School and the Mayo Clinic explored the impact of transplantation in producing senescence, a biological phenomenon connected to aging and age-related disorders, by transplanting older donor organs into younger recipients. The researchers transplanted hearts from young (3 months) and aged (18-21 months) mice into younger recipients.
When compared to patients who got young transplants, recipients who received elderly hearts exhibited higher frequencies of senescent cells in draining lymph nodes, livers, and muscles, as well as higher systemic mt-DNA levels. Surprisingly, aged organ transplantation resulted in not only advanced physical but also cognitive deficits in recipient animals.
Senolytics, a novel family of medications designed to directly target and remove senescent cells, were also discovered as a potential remedy to this process. When elderly donors were given Senolytics (Dasatinib and Quercetin) before organ donation, the transmission of senescence was dramatically decreased due to a decrease in the concentration of senescent cells and mt-DNA.
Recipients of elderly organs treated with Senolytics demonstrated enhanced physical fitness equivalent to findings in recipients of young organs.
“Donor age plays a crucial role in the success of transplantations, with recipients of older organs facing worse short- and long-term outcomes,” said Maximillian J. Roesel, who presented the work as part of the group at Brigham and Women’s Hospital, Harvard Medical School. Nonetheless, using older donor organs is critical to addressing the worldwide organ shortage, and this study exposes basic obstacles as well as potential solutions for employing older organs.”
The need for organ transplantation is increasing across Europe, owing to an increase in chronic illnesses. Furthermore, the rising demand significantly outnumbers the available supply of organs, with recent data showing that an average of 21 individuals die in Europe each day while waiting for a transplant.
“Moving forward, we will delve deeper into the mechanisms underlying our current findings, with a particular focus on Senolytics’ potential role in preventing the transfer of senescence in humans.” “This research is extremely exciting and clinically relevant because it may not only help us improve outcomes but also make more organs available for transplantation,” said senior and main author Stefan G. Tullius.