Heart transplants are limited by donor availability. Credit: Vsevolod Zviryk/Science Photo Library What happens to organs when they are transplanted? According to one study,1 young donor hearts age rapidly in the bodies of older recipients, and older hearts rejuvenate inside young ones. The findings, published on the preprint server bioRxiv and not yet peer-reviewed, imply that replacement organs could be obtained from people older than today. Heart transplants are being performed more frequently around the world and in older people, in part because people are living longer. In the United States, for example, there were a total of 4,636 heart transplants in 2024, 81.5% more than in 2013. Still, hundreds of people around the world die each year while on waiting lists for new organs. Generally, donors under the age of 45 are recommended, although older donors who do not show signs of significant coronary artery disease are also considered. Now, Jesse Poganik, who studies aging at Harvard University in Boston, Massachusetts, and his colleagues have investigated how donor hearts change their biological age (the amount of cellular damage they have accumulated) after transplant, in mice and in people. Young hearted old mice (1.5 to 1.67 years old) into mice from all three age groups so that they lived with both the graft and the native heart. Four to six months after the operation, they killed the mice and took tissue samples from them to measure their levels of DNA methylation (the addition or removal of chemical tags called methyl groups) in about 320,000 genetic regions, looking for changes related to the cellular damage of aging. They compared aging-related methylation levels in the grafted hearts with the levels in the animals’ original hearts. The analysis revealed that the biological ages of the donated hearts had changed to more closely match those of the recipients: younger hearts grafted into older animals showed accelerated aging, and old hearts were renewed in younger recipients. This aligns with previous work in which two living organisms were surgically joined together so that they shared a single circulatory system, a process known as parabiosis. Blood from young mice was found to prolong the life of the older mice they were connected to2 and improve their memory and learning. Blood from older mice can increase biological age in young mice 3. Host Rules Next, Poganik and his colleagues examined historic heart transplants at Brigham and Women’s Hospital in Boston, looking for those for which they could access biopsy samples for DNA methylation testing. They investigated 11 transplants with a substantial age difference between donor and recipient (8 to 24 years for older hearts grafted into younger people, and 38 to 50 years for younger hearts in older people). “What’s surprising is that we found exactly the same effects that we observed in mice,” says Poganik. The transplanted hearts had adopted the biological ages of their new hosts. The researchers also looked at the electronic medical records of hundreds of heart transplant recipients a year after the operation, to investigate how well their hearts were functioning and how this correlated with biological age. They found that measures such as heart rate, thickness of the posterior wall of the heart, and exercise capacity were associated with recipient age rather than donor age. “Some, but not all, functional measures followed the prediction that these older hearts in younger individuals functioned as if they were biologically younger, and vice versa,” Poganik says. “Some things are probably just irreversible.”
