Machine Perfusion Makes Donated Livers Biologically Younger, Study Finds

Once an organ is removed from a donor’s body, the clock starts ticking. Surgeons usually flush it with a preservative solution, bag it and put it on ice, where it immediately starts to degrade. They have hours to get it into a recipient. An increasingly popular alternative, especially for organs that are not in the healthiest state, is to put them on machines that pump them with nutrients and remove waste products, usually for around six to 12 hours. This allows doctors to assess the organs, and recent studies suggest that time spent on these perfusion machines helps them do better once they are transplanted.

Jesse Poganik, who studies aging at Brigham and Women’s Hospital in Boston and coauthored the study, and colleagues including Heidi Yeh and Alban Longchamp, transplant surgeons at Mass General Brigham, used aging clocks to assess donated livers. These are scientific tools designed to measure biological age, a result meant to convey more about the health status of an organ or person than chronological age. “If [we] can improve the utilization of organs beyond what the current systems can do, then that’s a win in my book,” Poganik says.

In an initial experiment, the team used a clock to look at patterns of chemical marks on DNA in 37 samples taken from 19 donated livers. Such epigenetic patterns are known to change as we age. When the team compared samples from livers kept on ice and those that were perfused, it found a striking pattern in the latter. “Machine-perfused livers, in spite of being older or having other disadvantageous characteristics, had a biological age that was lower than [non-perfused] livers that were chronologically younger,” says Yeh, who led the work.

To investigate further, Yeh and her colleagues analyzed another 208 samples from 103 donated livers. This time, they used different aging clocks, ones that essentially measure how genes are working. They studied samples biopsied from the livers after they had been stored for up to around six hours either in cold storage or on machine perfusion. In most cases, they also assessed a second sample taken around an hour after the livers had been transplanted into a recipient. Once the organ’s blood supply is reestablished in the body, “you have a few other things to do,” says Longchamp. “Then you just do a quick biopsy before you close.”

According to the clocks, which were developed to measure age and risk of death, the machine-perfused livers were biologically younger, the team found. “Pumping them at 34 degrees with oxygen and nutrients actually reversed the biological age,” says Longchamp. The results have been shared with colleagues at an industry conference, he says. “If you adjust out chronological age … to have a fair head-to-head comparison, the difference between the two is on the order of 30%,” says Poganik. “It’s logical to say that perfusion drives this effect.”

The biological ages of all the livers tended to increase as soon as they were put into a recipient’s body, probably as a result of stresses on the organs. Still, the effect endured: the perfused organs remained biologically younger. The researchers hope to find new ways to test the health of donated organs and potentially develop additional tools to repair organs that might otherwise be discarded.

Nathanael Raschzok, a transplant surgeon at Charité Universitätsmedizin Berlin in Germany who was not involved in the research, says the work is impressive. But it is not yet clear what these changes might mean for the recipients of these organs, he says. The organs in the study were donated by people in their 30s, 40s and 50s. Raschzok wants to know the effect of perfusion on the liver of an 80-year-old. “Every so often, we use organs from 70-, 80-, 85-year-old donors,” he says. A better understanding of why the organs appear to be getting biologically younger might lead to therapies that achieve the same effect with a drug that could potentially be used to treat a donated organ for a fraction of the price, he adds.

That matters because perfusion is expensive. Raschzok says it costs around €10,000 in Germany, a quarter of the budget for a transplant, while the cost in the US comes to around $80,000 to $100,000 per organ, says Yeh.