Donated livers can be made biologically younger
Once an organ is removed from a donor’s body, the clock starts ticking. Surgeons usually flush the organ with a preservative solution, bag it, and put it on ice—where it immediately starts to degrade.
When a donated organ is removed from a donor’s body, it starts to degrade quickly. Surgeons have two main ways to preserve it before transplantation. The first method involves flushing the organ with a preservative solution (like the University of Wisconsin solution), placing it in a sterile bag, and storing it on ice. This is called cold storage and is the most common approach. The second method, growing in popularity, uses perfusion machines that pump the organ with oxygen and nutrients for 6 to 12 hours, mimicking conditions inside a living body. This process allows doctors to assess the organ’s health and may improve its function after transplantation. Perfusion machines cost between €10,000 in Germany and $80,000 to $100,000 in the US per organ, which is a significant expense compared to the overall transplant budget.
Biological age refers to how old an organ or person appears at a molecular level, based on chemical changes to DNA and gene activity, rather than its actual age in years (chronological age). Scientists use aging clocks—tools that analyze patterns in DNA or gene activity—to measure biological age. These clocks help predict health risks and outcomes. For example, a 50-year-old organ with a biological age of 40 might function better than a 40-year-old organ with a biological age of 50. In this study, researchers used aging clocks to compare livers preserved by cold storage and perfusion, finding that perfused livers appeared biologically younger despite their chronological age.
Researchers from Brigham and Women’s Hospital and Mass General Brigham analyzed liver samples from 19 and 103 donors using aging clocks. They found that livers preserved with perfusion machines showed signs of reversed biological aging—their biological age was up to 30% lower than livers preserved on ice, even when comparing organs of the same chronological age. The perfusion process, which involves pumping the liver at 34 degrees Celsius (93.2°F) with oxygen and nutrients, activated cell pathways linked to reduced inflammation, tissue repair, and the removal of damaged cell parts. However, once transplanted, the biological age of perfused livers increased again due to the stress of surgery, though they remained younger than non-perfused livers.
The study suggests that perfusion could improve transplant outcomes by making older or less healthy organs function more like younger ones. Before perfusion machines became widely used, surgeons often avoided livers from donors over 40 who had suffered circulatory death (when the heart stops beating, reducing blood flow to organs). Today, livers from donors over 70 are being used successfully thanks to perfusion. While the research shows promising molecular changes, it is unclear how these translate to long-term benefits for recipients. Transplant surgeon Nathanael Raschzok, not involved in the study, notes that the effect of perfusion on organs from very elderly donors (e.g., 80 years old) remains unknown.
The research team aims to develop tests that assess an organ’s biological age to determine its suitability for transplantation. They are also exploring drug treatments that could mimic the effects of perfusion, potentially at a lower cost. Currently, perfusion is expensive and not universally available, limiting its use. The study highlights the need for further research to understand why perfusion reverses aging signs and whether this leads to better patient outcomes. In the meantime, perfusion is already expanding the pool of usable organs, transforming transplant surgery practices in recent years.
