Aged Transplant Organs Cause Harm to Younger Recipients
Old tissues are dysfunctional in ways that young tissues are not. In the context of organ transplants, it has been recognized that aging cells can have a negative impact on outcomes for younger recipients, but until recently, there have been limited measures to address this issue. However, there is now a growing understanding of the role of senescent cells in degenerative aging, and the development of senolytic therapies, such as the dasatinib and quercetin combination, offers a new approach to improve the quality of transplanted organs and patient outcomes.
Most organ transplantations involve supply from older donors to younger recipients. Aging cells can become senescent, a condition in which they stop multiplying and secrete chemicals that negatively affect neighboring cells. Senescent cells accumulate in older donor organs, and have the potential to compromise transplant outcomes.
A study found that in preclinical animal models, transplanting older organs can trigger senescence in younger recipients. They observed that young and middle-aged mice that received heart transplants from older mice had impaired physical capacity, with reduced running times and grip strengths. Middle-aged mice who received older hearts also showed increased anxiety-related behavior, impaired memory, and poorer learning performances.
Researchers found that these accelerated aging-related effects in younger recipients were driven by the release of senescence-associated factors and mitochondrial DNA from older transplants. Treating older donor mice with senolytics, or senescence-inhibiting drugs, before organ extraction reduced symptoms of senescence in the recipient mice.
Link: https://www.eurekalert.org/news-releases/1010194
