Transplanted Hearts Adopt Host’s Biological Age, Study Finds

Organs used in transplants undergo significant biological changes after being moved to a new host, with heart tissue from younger donors aging quickly in older recipients and older hearts rejuvenating within younger patients. These findings, published on the preprint server bioRxiv, suggest that the current limits on donor age for heart transplants may be unnecessarily restrictive.

Heart transplant procedures are becoming increasingly common globally, particularly among elderly patients, driven in part by rising life expectancy. In the United States alone, 4,636 transplants were performed in 2024, marking an 81.5% increase from 2013 levels. Despite this rise, hundreds of patients worldwide continue to die annually while waiting for compatible organs, prompting efforts to expand the available donor pool through alternative methods such as xenotransplantation from pigs or relaxing guidelines on donor age.

Currently, most guidelines recommend using hearts from donors under 45 years old, though older donors without significant coronary artery disease are also considered. Jesse Poganik, an aging researcher at Harvard University in Boston, and his colleagues investigated how the biological age—defined by accumulated cellular damage—of donor hearts shifts post-transplant in both mice and humans.

In the mouse model, the team grafted extra hearts from young (three-month-old), middle-aged (one-year-old), and old (1.5 to 1.67-year-old) mice into recipients of corresponding ages. Four to six months after surgery, the researchers analyzed DNA methylation levels across approximately 320,000 genetic regions in both the grafts and the animals’ native hearts. The data showed that grafted hearts adjusted their biological age to align closely with that of the recipient, with younger hearts showing accelerated aging in older hosts and older hearts appearing refreshed in younger recipients.

This phenomenon mirrors previous parabiosis studies, where surgically joining two organisms to share a circulatory system demonstrated that young blood could extend the lifespan and improve cognitive function in older mice, while old blood had the opposite effect on younger subjects.

To validate these results in humans, the researchers examined historical transplant data from Brigham and Women’s Hospital in Boston, focusing on 11 cases with substantial age gaps between donor and recipient. They found the same patterns observed in mice: transplanted hearts adopted the biological age of their new hosts.

The team also reviewed electronic medical records of hundreds of heart-transplant recipients one year post-operation to assess how well the organs functioned relative to their biological age. Metrics such as heart rate, posterior wall thickness, and exercise capacity correlated more strongly with the recipient’s age than the donor’s. Poganik noted that while some functional indicators supported the prediction that older hearts function as biologically younger in younger patients, certain age-related damage remains irreversible.