Demand for heart transplants is growing, but donor hearts are a scarce resource. Age further narrows the pool, with doctors preferring younger hearts because older organs have been linked to worse outcomes.
But a new preprint posted to the server bioRxiv suggests that age might not be such a limit after all—and, incredibly, that transplanted organs may change to mirror the age of the recipient, not the donor. Ultimately, the findings suggest an old heart can become biologically “younger” after being transplanted into a younger recipient.
Jesse Poganik, an instructor in medicine at Harvard Medical School and co-author of the study, and his colleagues transplanted hearts between young, middle-aged and old mice while keeping each recipient’s native heart intact. They measured DNA methylation, a type of chemical mark that changes with age, and used three epigenetic clocks—measures of those chemical changes—to estimate the grafts’ biological age.
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Young hearts transplanted into older mice appeared biologically older than expected, while old hearts placed in younger mice appeared to have de-aged. Other tests of biological aging showed the same pattern.
“My interpretation of these results is that the young systemic environment can reverse certain aspects of biological age, but others may be irreversible,” Poganik says.
The findings suggest organs are responsive to their environment, says Peter Scriven, co-founder and clinical and scientific director at LONGEVITY, an aging clinic in England, who was not involved in the study. “That gives us a reason to ask how much of its aging we can change.”
Exactly what is happening to change the organs’ age markers is unclear. Poganik suspects the overall body environment, rather than any one factor, may help clear accumulated damage or expose the organ to younger immune factors.
Genes involved in the function of mitochondria—the powerhouses of the cell—also became more active in old hearts placed in young mice and less active in young hearts placed in old mice. “What excites me most is the possibility of transferable rejuvenation factors,” Scriven says, pointing to mitochondrial activity and other antiaging signals potentially passing from recipient cells to the transplanted heart. In the future, healthy mitochondria might even be harnessed to rejuvenate an organ, he says.
The transplant did not appear to change the biological age of the recipient’s own heart (which stayed in the body), liver or blood. Transplantation itself, however, also caused pro-aging changes, including increased inflammation.
Michael Sagner, clinical adviser in longevity and preventive medicine at King’s College London, who was not involved in the study, says the study’s methods have some limitations. “Existing models such as the ones used in the study are still experimental and not necessarily an expression of real biological age yet,” he explains.
To strengthen the results, however, the team analyzed archived heart biopsies from 11 human transplant recipients with large donor-recipient age gaps. Again, the transplanted hearts’ biological ages were more closely associated with the recipient’s age than the donor’s.
By analyzing a database of hundreds of human transplant recipients, the researchers also found that some functional measures of heart health also tracked more closely to recipient age. Most notably, exercise capacity and VO2 max, a measure of the body’s ability to use oxygen during exercise, were lower in older recipients regardless of the donor’s age, suggesting the transplanted heart was aging alongside the rest of the body.
“It may be the case that older organs that would currently be passed over for donation could be considered for younger recipients,” Poganik says, noting that much more work is needed before any changes to the donor system might be implemented.