In a groundbreaking development poised to revolutionize organ transplantation, scientists have discovered that donated livers can be made biologically younger and demonstrably healthier through a process known as machine perfusion. This innovative technique, which involves pumping donated organs with nutrient-rich solutions and removing waste products, is not only extending the viability of organs but also reversing cellular aging at a molecular level. The implications of this research are profound, potentially increasing the number of viable donor organs, improving transplant success rates, and ultimately saving more lives.

The conventional approach to organ preservation after donation involves flushing the organ with a preservative solution, packaging it in ice, and transporting it to the recipient within a critical, time-sensitive window of a few hours. During this period, the organ inevitably begins to degrade, a race against time that often limits the usability of organs from donors who may not be in peak health. However, an alternative gaining traction is machine perfusion, where organs are placed on specialized machines for six to twelve hours. This process mimics being back in a living body, allowing organs to receive a continuous supply of oxygen and nutrients while waste is efficiently removed.

Recent studies have already suggested that organs subjected to machine perfusion perform better post-transplantation. Now, new research, shared exclusively with MIT Technology Review, offers compelling molecular evidence that this perfusion process effectively makes organs biologically younger. This finding could shed light on why organs from younger donors historically exhibit higher success rates and explain the reduced likelihood of organ failure observed in perfused organs after transplantation.

The researchers behind this transformative study aim to develop more sophisticated methods for assessing the health of donated organs and to create new tools for repairing organs that might otherwise be deemed unsuitable for transplantation. Jesse Poganik, a researcher specializing in aging at Brigham and Women’s Hospital in Boston and a coauthor of the study, expressed his enthusiasm, stating, "If [we] can improve the utilization of organs beyond what the current systems can do, then that’s a win in my book."

Clocking Organs: Measuring Biological Age

To unravel the impact of machine perfusion on organ health, Poganik, along with transplant surgeons Heidi Yeh and Alban Longchamp from Mass General Brigham, employed "aging clocks." These sophisticated scientific tools are designed to measure an organ’s biological age, offering a more accurate reflection of its true health status than its chronological age.

In an initial experiment, the team analyzed epigenetic patterns – chemical modifications on DNA known to change with age – in 37 samples from 19 donated livers. They observed a "striking" difference between livers kept on ice and those that underwent machine perfusion. Heidi Yeh, who led this crucial phase of the work, explained, "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."

To further validate these findings, Yeh and her colleagues expanded their analysis to 208 samples from 103 donated livers. This time, they utilized different aging clocks that measure gene activity. They examined liver samples biopsied after approximately six hours of storage, comparing those kept in cold storage with those on machine perfusion. Additionally, they assessed a second sample taken about an hour after the livers were transplanted into recipients, a standard procedure for monitoring post-transplant organ function.

The results consistently showed that machine-perfused livers were biologically younger, according to the aging clocks. Alban Longchamp noted, "Pumping them at 34 degrees with oxygen and nutrients actually reversed the biological age." He further elaborated that even after accounting for chronological age in a fair comparison, the difference between the two groups was approximately 30%, strongly suggesting that perfusion is the driving factor behind this rejuvenation. While the biological age of all livers tended to increase once reinserted into a recipient’s body due to the stresses of transplantation, the beneficial effect of perfusion persisted, with these organs remaining biologically younger.

Nathanael Raschzok, a transplant surgeon at Charité Universitätsmedizin Berlin who was not involved in the study, hailed the research as "impressive." However, he raised pertinent questions about the long-term implications for recipients, particularly concerning organs from older donors. He emphasized the increasing use of organs from donors in their 70s and 80s and expressed interest in how perfusion might affect livers from such individuals.

Raschzok also highlighted the significant cost associated with machine perfusion. He estimated the cost in Germany to be around €10,000, representing a quarter of a transplant’s budget, while in the US, it can range from $80,000 to $100,000 per organ, according to Yeh. He suggested that a deeper understanding of why organs become biologically younger through perfusion could pave the way for developing less expensive therapeutic alternatives, such as drugs, to achieve similar rejuvenating effects.

Molecular Repair: Unveiling the Mechanisms of Rejuvenation

While the researchers couldn’t always examine the livers before perfusion due to procedural norms, analyzing the altered genes and molecular pathways in perfused organs provided crucial insights. At a molecular level, the team identified changes in cell pathways associated with inflammation and tissue structure. Notably, they observed increased activity in a pathway responsible for cellular repair and recycling of damaged components, suggesting a direct molecular mechanism for organ rejuvenation.

Poganik expressed his hope that this research will lead to the development of tests capable of identifying organs most suitable for transplantation based on their biological age. His team is also actively exploring potential drug treatments that could further reduce an organ’s biological age.

Yeh concluded that any liver not originating from a "perfect, young, brain-dead donor" could likely benefit from perfusion. She underscored the transformative impact of perfusion technology on transplant surgery. Just a few years ago, she recalled, surgeons would typically avoid livers from donors who had experienced circulatory death and were over 40. Today, livers from such donors aged over 70 are routinely used. "Perfusion has completely changed the landscape of transplantation in the last three years," she affirmed, highlighting its pivotal role in expanding the donor pool and improving patient outcomes.