Patients who receive organs from older donors are more at risk of age-related diseases, a new study shows. As a potential solution, researchers suggest the use of a new class of drugs, called senolytics, which prevents the transfer of a key aging mechanism during organ transplants.
Senolytic is a class of drugs that can selectively clear senescent cells. As people age, senescent cells accumulate in the body and these cells are associated with several age-related illnesses such as cancer, diabetes, osteoporosis, cardiovascular disease, stroke, Alzheimer’s disease and osteoarthritis.
In the latest study, presented at the European Society for Organ Transplantation (ESOT) Congress 2023, researchers from Harvard Medical School and the Mayo Clinic analyzed how transplantation can induce senescence or aging in patients who receive older organs.
“Donor age plays a crucial role in the success of transplantations, with recipients of older organs facing worse short- and long-term 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 utilizing older organs,” Maximillian J. Roesel, who presented the study, said in a news release.
In a mice experiment, researchers studied the impact of heart transplants from young mice (three months) and old (18–21 months) mice in younger recipients.
Researchers found both physical and cognitive impairments in the recipients who got organs from older donors. The recipients who got older hearts showed a higher occurrence of senescent cells in lymph nodes, livers and muscles compared to the younger heart recipients. However, treatment with senolytics in donors improved the physical fitness of the recipients.
“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,” the researchers said.
More than 100,000 people are awaiting transplantation in the U.S. and 17 people die every day waiting for an organ to become available.
Researchers hope the findings will help to expand the current organ donor pool and enhance patient outcomes in transplants.
“Moving forward, we will delve deeper into the mechanisms underpinning our current findings, with a particular focus on the potential role of Senolytics in preventing the transfer of senescence in humans. This research is extremely exciting and clinically so relevant as it may not only help us to improve outcomes but also make more organs available for transplantation,” said Stefan G. Tullius, a senior and lead author of the study.
Published by Medicaldaily.com