Heart transplants may change an organ’s biological age, study finds

What happens to an organ after it is transplanted? Research suggests that hearts from young donors can age rapidly in older recipients, while older hearts may become biologically younger in younger people.¹ The findings, reported in a preprint posted on bioRxiv and not yet peer-reviewed, could broaden the pool of donor hearts available for transplantation.

Heart transplants are being performed more frequently around the world, including in older people, partly because people are living longer. In the United States, 4,636 heart transplants were performed in 2024 — an 81.5% increase over 2013. Yet hundreds of people die each year around the world while waiting for an organ transplant.

These shortages have prompted efforts to transplant organs grown in pigs into humans. Guidelines have also changed in many places to increase the number of human hearts available for transplantation. Donors younger than 45 are generally preferred, although older donors without signs of significant coronary artery disease may also be considered.

Jesse Poganic, who now studies ageing at Harvard University in Boston, Massachusetts, and his colleagues investigated how a donor heart’s biological age changes after transplantation in mice and humans. Biological age reflects the amount of cellular damage accumulated over time.

Young hearts age faster in older recipients

The researchers transplanted extra hearts from young mice, aged 3 months; middle-aged mice, aged 1 year; and old mice, aged 1.5 to 1.67 years, into mice from all three age groups. This allowed the animals to live with both their transplanted and natural hearts.

Four to six months after surgery, the mice were euthanized and tissue samples were collected. The researchers measured DNA methylation — the addition or removal of chemical tags called methyl groups — in about 320,000 genetic regions. They looked for methylation patterns associated with cellular ageing and compared the transplanted hearts with the animals’ native hearts.

The analysis showed that the biological age of transplanted hearts shifted towards the biological age of their recipients. Young hearts transplanted into older animals showed accelerated ageing, whereas older hearts appeared to become biologically younger in young recipients.

The findings are consistent with previous research on parabiosis, a procedure in which two organisms are surgically joined so that they share a circulatory system. Blood from young rats has been found to extend the lifespan of older rats with which they were connected² and improve memory and learning. Blood from older mice can increase the biological age of young mice.³

The recipient’s body may shape a transplanted heart

Poganic and his colleagues then examined previous heart transplants at Brigham and Women’s Hospital in Boston. They identified cases with biopsy samples suitable for DNA methylation testing. The researchers studied 11 transplants involving substantial age differences between donors and recipients: 8 to 24 years when an older heart was transplanted into a younger person, and 38 to 50 years when a younger heart was transplanted into an older person.

“What’s remarkable is that we found exactly the same effect that was observed in mice,” Poganic says. The transplanted heart took on the biological age of its new host.

The researchers also examined electronic medical records from hundreds of heart-transplant recipients one year after surgery. They assessed how well the transplanted hearts were functioning and whether their performance correlated with the biological age of the organ.

Measurements including heart rate, the thickness of the heart’s posterior wall and exercise capacity were associated with the recipient’s age, but not the donor’s age. “Some, but not all, functional measurements tracked the prediction that ageing hearts in young people would function as if they were biologically young, and vice versa,” Poganic says. “Maybe it’s irreversible.”