UF researchers make breakthrough in transplanting older livers
Published: Saturday, January 1, 2011 at 3:02 p.m.
Last Modified: Saturday, January 1, 2011 at 3:02 p.m.
University of Florida researchers have identified a key cellular process that ultimately could help shorten the waiting list of 16,904 Americans in need of a liver transplant.
The process involves ways to reverse age-related damage to the liver by manipulating genes or administering certain drugs.
It would enable transplant surgeons to make use of livers donated by older adults.
"If we could improve the function and health of livers, and increase donations from seniors, we can significantly improve the success rate of transplantations," said Jae-Sung Kim.
Kim is an assistant professor of surgery in the UF College of Medicine and a member of the UF Institute on Aging. He led the research team that made the discovery.
The liver performs many vital and complex jobs, including turning food into usable nutrients and removing toxins from the body.
But just as our brains and muscles lose function as we age, the liver also becomes less resilient. As a result, livers donated by older adults are frequently unusable because of the increased risk of failure. Those who do get livers from older donors often need a second transplant within a year.
Surgery to remove parts of the liver (or transplant the entire organ) involves clamping off the blood vessels and temporarily depriving the liver of blood flow and oxygen. Suddenly restoring blood and oxygen after surgery can cause stress-related injury to the organ. Younger livers rebound readily, but older livers have great difficulty recovering function after the injury.
In laboratory studies, Kim and his colleagues found that when the process of clearing away damaged mitochondria, the energy centers of cells, is disrupted, aged livers are unable to recover. An age-related decrease in levels of the protein Atg4B orchestrates the process.
The researchers used gene therapy to replenish the depleted supplies of Atg4B, boosting the performance of livers from older animals beyond that of normal middle-aged animals.
Kim and colleagues, including Christiaan Leeuwenburgh, professor and chief of the biology of aging division, hope the findings will make their way into clinical applications. They now are testing various drugs to see which can mimic the results in the animal model with minimal side effects.
"The basic mechanisms discovered here will lead to the next step in helping transplant surgeons find tools and ways to spur some of the pathways that are failing, and allow organs from older individuals to be successfully transplanted," Leeuwenburgh said.