Once an organ is removed from a donor's body, time becomes a critical factor. Surgeons typically flush the organ with a preservative solution, place it in a bag, and store it on ice. However, this method causes the organ to degrade relatively quickly, leaving doctors with only a few hours to transplant it into a recipient. To extend the viability of organs, some hospitals use perfusion machines—devices that circulate nutrients and remove waste, mimicking the body’s natural processes. These machines can keep organs functional for up to 12 hours, giving surgeons more time to assess their quality and potentially improve their chances of successful transplantation. Recent research suggests that organs treated with perfusion may perform better after being transplanted, possibly because the process helps "rejuvenate" them at a molecular level. Scientists have uncovered molecular clues that may explain why organs from younger donors tend to have higher success rates and why perfused organs are less likely to fail after transplantation. Researchers, including Poganik and colleagues at Mass General Brigham, used "aging clocks"—tools that measure biological age, which reflects an organ's health rather than just its chronological age—to analyze donated livers. In one study, they examined DNA samples from 37 livers and found that those stored on perfusion machines showed a lower biological age compared to those kept on ice. This was particularly striking because the perfused livers came from older donors. Additional experiments with 208 liver samples confirmed that machine-perfused livers were biologically younger, even when compared to younger organs. The process of pumping the livers with oxygen and nutrients at a body-like temperature appeared to reverse their biological age. Despite these improvements, the biological age of all livers increased once they were transplanted into recipients, likely due to the stress of the procedure. However, the perfused organs remained biologically younger than their non-perfused counterparts. Transplant surgeon Nathanael Raschzok, not involved in the study, called the findings impressive but noted that the long-term impact on recipients remains unclear. The study focused on organs from donors in their 30s, 40s, and 50s, and Raschzok is interested in understanding how perfusion might affect livers from much older donors, such as those in their 70s or 80s. Understanding the molecular mechanisms behind the rejuvenation effect could lead to new therapies that mimic perfusion’s benefits using drugs, which would be significantly cheaper than the current perfusion process. Perfusion is expensive, costing around €10,000 in Germany and up to $100,000 in the U.S. per organ. Researchers are also exploring ways to test the biological age of organs before transplantation, which could help determine which ones are most suitable for use. Meanwhile, perfusion has already transformed transplant practices. Surgeons who once avoided using livers from older donors or those who had suffered circulatory death are now using them more frequently, thanks to the improved viability offered by perfusion. As research continues, the goal is to further enhance the success rates of organ transplants, making life-saving procedures more accessible and effective.