Donor hearts transplanted into mice and humans alter their biological age to match their new hosts, according to preprint research led by Harvard scientists. The findings show old hearts rejuvenated in young recipients while young hearts aged faster in older bodies, potentially widening future donor criteria.
How Transplanted Hearts Shift Biological Age in Mice and Humans
When a heart moves from one body to another, its cellular clock does not stay frozen. A study posted on the preprint server bioRxiv reveals that transplanted organs adjust their molecular wear to mirror their new environment, a discovery that challenges long-held assumptions about organ aging according to Nature reporting.
Led by Jesse Poganik at Harvard University, researchers investigated DNA methylation—the addition and removal of chemical tags that track cellular damage over time—in both animal models and clinical archives. The team grafted hearts from young, middle-aged, and old mice into recipients across all three age groups while leaving the native hearts intact. Four to six months later, tissue analysis across roughly 320,000 genetic regions showed that the biological ages of the grafted hearts had migrated toward those of their hosts. Younger hearts aged rapidly inside older mice, whereas older hearts showed distinct signs of rejuvenation within younger recipients.
Historical Biopsies Confirm Human Organ Changes
To test whether the mouse data translated to humans, Poganik and his colleagues examined historical records and stored biopsy samples from Brigham and Women’s Hospital in Boston. They focused on 11 heart transplants featuring substantial age gaps between donors and recipients, ranging from 8 to 24 years for older hearts placed in younger individuals, and 38 to 50 years for younger hearts placed in older individuals.
The remarkable thing is that we found exactly the same effects that we saw in the mice.
Jesse Poganik, who studies ageing at Harvard University, via Nature
DNA methylation testing on those human biopsy samples confirmed that the transplanted organs had adopted the biological age of their new hosts.
Addressing the Global Organ Shortage and Donor Guidelines
The implications for transplant medicine arrive as demand heavily outpaces supply. In the United States alone, physicians performed 4,636 heart transplants in 2024—an 81.5% increase compared to 2013. Despite this rise, hundreds of patients continue to die each year while waiting for a viable organ according to data published by Nature.
Current clinical guidelines generally recommend donors younger than 45 years old, though older individuals without significant coronary artery disease are occasionally evaluated. If peer review validates the preprint findings, surgeons might eventually reconsider older organs that are routinely discarded under the assumption that they will underperform reported MIT Technology Review.
Biological Complexity and Unresolved Mechanisms
Despite the striking shifts in DNA methylation, scientists emphasize that aging remains deeply complex and certain cellular degradations are likely permanent. Poganik noted that not all functional measures followed the rejuvenation pattern, suggesting that some age-related damage cannot be undone simply by changing the systemic environment.
My interpretation of these results is that the young systemic environment can reverse certain aspects of biological age, but others may be irreversible.
Jesse Poganik, instructor in medicine at Harvard Medical School, via Scientific American
João Pedro de Magalhães, who studies aging at the University of Birmingham in the UK and was not involved in the project, suggests that circulating immune cells or dilution effects from an older recipient’s body could influence how new organs react noted MIT Technology Review. Prospective clinical studies must confirm whether functional gains persist long-term and whether utilizing older human donors impacts rejection or failure rates before any systemic changes to organ allocation can occur.
