Hearts appear to change their biological age after transplantation, with young donor organs showing accelerated ageing in older recipients and older hearts displaying signs of rejuvenation when placed in younger bodies, according to research reported by Nature.
The findings, from a study led by Jesse Poganik, an ageing researcher at Harvard University, suggest that the biological ageing of a transplanted organ may be influenced by the body in which it is placed. The study was posted on the bioRxiv preprint server and has not yet undergone peer review, meaning its findings require confirmation through further research.
The research could have implications for the supply of donor organs. Heart transplantation is increasingly being performed worldwide, including in older patients, as populations live longer. In the United States, 4,636 heart transplants were carried out in 2024, an increase of 81.5% from 2013. At the same time, people continue to die while waiting for suitable organs.
Existing efforts to expand the supply include the experimental transplantation of genetically modified pig organs into humans and changes to guidelines governing the use of older human donor hearts. Donors younger than 45 are generally preferred, although older hearts may also be accepted when they show no significant coronary artery disease.
Poganik and his colleagues first investigated the phenomenon in mice. They transplanted additional hearts from young mice aged three months, middle-aged mice aged one year and older mice aged between 1.5 and 1.67 years into animals from all three age groups. The recipient mice therefore retained their own hearts while also carrying the transplanted organs.
Four to six months later, the researchers examined tissue from the grafted and original hearts. They analysed DNA methylation across about 320,000 genetic regions. DNA methylation involves chemical tags attached to DNA and can provide measures associated with biological ageing and accumulated cellular damage.
The results showed that transplanted hearts moved towards the biological age of their recipients. Young hearts placed in older mice showed signs of accelerated biological ageing, while older hearts transplanted into younger mice displayed changes associated with a younger biological age.
The findings are consistent with earlier research involving parabiosis, in which two animals are surgically connected so that they share a circulatory system. Studies in mice have found that exposure to young blood can extend the lifespan of older animals and improve aspects of memory and learning, while exposure to older blood can increase biological-age measures in younger animals.
The researchers then examined human heart transplants performed at Brigham and Women’s Hospital in Boston. They identified 11 cases with substantial age differences between donors and recipients for which biopsy samples were available. The age gap ranged from eight to 24 years among older hearts transplanted into younger recipients and from 38 to 50 years among younger hearts transplanted into older recipients.
The human results showed the same general pattern observed in the mice. According to Poganik, the transplanted hearts appeared to take on biological characteristics associated with the age of their new hosts.
The team also examined medical records from hundreds of heart-transplant recipients one year after transplantation. Several measures of heart function, including heart rate, posterior-wall thickness and exercise capacity, were associated more closely with the recipient’s age than with the donor’s age.
Poganik cautioned, however, that not every functional measurement followed the predicted pattern. Some characteristics of an organ may be irreversible and may not respond to the biological environment of its new host. The researchers also found no evidence that transplanting a heart altered the biological functions of other organs in the recipient.
Cardiac surgeon Bartley Griffith of the University of Maryland School of Medicine, who performed the first transplant of a genetically modified pig heart into a human in 2022, described the findings as consistent with emerging research into ageing and circulating blood factors.
The study’s authors say larger studies involving more patients and different transplant programmes will be needed before the findings can influence clinical practice. Nevertheless, the research raises the possibility that older donor hearts could be used more extensively if their biological ageing can be influenced by younger recipients.
Amy Fiedler, a cardiac surgeon at the University of California, San Francisco, said there remains reluctance to transplant hearts from older donors into younger patients because of concerns about how long the organs will function.
The findings reported by Nature therefore point to a potential new consideration in organ allocation: the chronological age of a donor heart may not fully determine how the organ ages after transplantation.
