Researchers at Harvard Medical School and Mayo Clinic have identified that senolytic drugs can reduce the risk of physical and cognitive decline when organs from older donors are transplanted. In parallel work conducted in aged mice, these drugs also improved overall health and physical performance. The study was presented at ESOT 2023, the European Congress of Transplantation.
In the experimental setup, scientists transplanted hearts from two age groups of mice—young (about three months old) and aged (approximately 18 to 21 months old)—into younger recipient mice. Recipients of older hearts showed higher levels of senescent cells in key tissues such as lymph nodes, the liver, and skeletal muscles. Beyond physical fatigue, aged donor organs were linked to observable cognitive challenges in the recipient animals, underscoring how donor aging can influence transplant outcomes on multiple axes.
The team tested senolytics, a novel class of drugs aimed at eliminating senescent cells. By administering dasatinib and quercetin to aged donor mice prior to organ harvesting, researchers achieved a notable reduction in senescent cell burden in the donors. This pre-treatment correlated with improved post-transplant physical function in the recipients, suggesting a potential strategy to mitigate age-related problems after transplantation.
“Donor age is a significant factor affecting both short- and long-term transplant success. While there is a pressing need to expand the donor pool, the findings point to strategies that could make older donor organs safer and more effective for recipients,” explained Maximilian J. Rosel, the study’s lead author.
These findings align with ongoing efforts to address the global organ shortage through broader use of organs from older donors, while simultaneously seeking methods to preserve and enhance their function after transplantation. The research adds a new dimension to the discussion by showing how targeted cellular therapies may influence transplant outcomes at the cellular and systemic levels.
Historically, scientists have explored various approaches to extend organ viability and performance after transfer. The current work demonstrates that pre-emptive cellular cleansing in donor animals can yield tangible benefits in recipients, potentially reducing complications and improving quality of life after surgery. While these results come from animal studies, they offer a compelling rationale for further investigation in human clinical trials and may inform future guidelines for the utilization of older donor organs.
In summary, the collaboration between HMS and Mayo Clinic highlights a promising path forward in transplant medicine. By pairing donor selection with senolytic strategies, the medical community could enhance post-transplant outcomes for older organs while addressing the wider issue of organ scarcity. This line of inquiry continues to be a focal point in transplant research, with the potential to reshape how aging organs are evaluated and used in clinical practice. The study contributes to a growing body of evidence supporting aging-friendly approaches to transplantation and underscores the importance of translating laboratory findings into therapies that can benefit patients in real-world settings. The authors emphasize the need for careful clinical validation to determine safety, efficacy, and optimal treatment windows in humans, as the field moves toward broader application of senolytic strategies in transplantation.
Previous efforts to alleviate donor organ shortages have considered expanding eligibility criteria and improving organ preservation techniques. The current results add a biological lever—senescent cell clearance—that could complement these strategies and help ensure better outcomes for recipients of older donor organs, ultimately contributing to more sustainable and equitable transplantation practices.
Notes from the research team indicate that the emphasis on donor age should be paired with ongoing assessment of long-term benefits and risks, including how senolytics interact with other medications and the transplant ecosystem. The dialogue surrounding these findings continues to evolve as researchers explore the translational pathway toward human studies and potential clinical use, aiming to balance urgency with thorough safety evaluation.