Unpublished conference data link machine perfusion of donor livers to lower biological age estimates
Unpublished conference data link machine perfusion of donor livers to lower biological age estimates
On September 14, MIT Technology Review reported on results from a Boston team presented at an industry conference. In two series of molecular measurements, biological age estimates were lower in livers that underwent machine perfusion than in livers stored on ice.
After a liver is removed from a donor, surgeons must prepare it for transplantation quickly. The standard approach is to flush the organ with a preservation solution and cool it. In machine perfusion, the liver is connected to a device at roughly 34 °C: the device pumps oxygen and nutrients through the organ, removes waste products, and allows the team to assess the organ's condition before surgery.
The team examined 37 samples from 19 livers using epigenetic markers, chemical marks on DNA that change with age. In a second series, 208 samples from 103 livers were assessed by gene expression. These two independent methods of measurement made it possible to compare tissues after perfusion with tissues after ice storage.
In both series, biological age estimates were lower in the perfused livers, even though these organs often came from older donors or from donors whose organs surgeons had rated as less suitable for transplantation. After adjusting for chronological age, the difference between the groups was approximately 30%. After transplantation, the estimates rose in both groups and remained lower in the perfused livers.
In the same samples, the activity of genes involved in inflammation and tissue structure had shifted, and cells were more actively clearing damaged components. These changes accompanied the lower biological age estimates.
In a randomized trial from 2022 involving 300 recipients, normothermic perfusion reduced early graft dysfunction from 31% to 18%. The new data add a molecular assessment of each organ's condition before surgery to that clinical outcome.
The perfusion system also makes it possible to deliver drugs directly into the liver before the operation. In separate work, the compound FXT-001 was added to the perfusion fluid to protect cell membranes from oxidative damage. The team behind the current study is testing pharmacological treatments of the liver during perfusion; biological age assessment may reveal how such preparation changes the tissue.