Hundreds of people die each year while waiting for the right organ to perform a high-stakes transplant surgery. It’s the kind of resource scarcity that has led to some daring alternatives, including artificial hearts and animal-to-human “xenotransplant” experiments. But, if those two options leave you a little squeamish, how would you feel about receiving a replacement human heart with a bit of an age gap?
Long story short, it might work out surprisingly well. Harvard biochemical researcher Jesse Poganik and his collaborators in Boston discovered something peculiar in animal experiments that led them to drill down into 11 human heart transplant cases where there had been a significant age disparity between the donor and recipient. Working with biopsy samples from these transplant patients, Poganik’s lab ran DNA-methylation tests, measures of aging at the cellular level.
The results matched their animal tests. This sounds like a Hallmark movie, but the older hearts started to look and act like the younger people they were paired with, and the younger hearts started to look and behave more like old souls.
Poganik’s lab also triple-checked this against the electronic medical records of hundreds more heart-transplant recipients—finding that metrics like heart rate, exercise endurance, and the heart’s posterior-wall thickness more closely resembled the recipient’s age than the donor’s age.
“The remarkable thing is that we found exactly the same effects that we saw in the mice,” Poganik told the journal Nature. “Some, but not all, functional measures tracked the prediction that these older hearts in younger individuals functioned as if they were biologically younger, and vice versa.”
Without missing a beat
As Poganik and his coauthors noted in their study, now on bioRxiv, their results were “particularly surprising given the large chronological age disparities between donors and recipients in the profiled cohort.” The age gaps were roughly 8 to 24 years for older hearts surgically inserted into younger patients and 38 to 50 years for younger hearts grafted into older patients—decades-spanning gaps that these new hearts managed to overcome.
Poganik’s team, which focuses on the science of aging (perhaps obviously with the hope of reversing it), said that there were already promising candidates to explain these transplants’ unusual behavior. The team conducted broad analyses of each heart’s available RNA and the so-called transcriptomic pathways by which that RNA regulates physiological processes, finding the biggest shifts in genes tied to the hearts’ mitochondria and energy metabolism.
“Complementary work has shown that transplantation of old organs has also been shown to promote senescence [aging] in recipient tissues […] including mitochondrial DNA, consistent with mitochondria as a central node in age-related graft-recipient crosstalk,” the team noted.
There’s promising data here, in other words, toward identifying what parts of the body most contribute to aging. And it’s looking like it might be mitochondria, the notorious powerhouse of the cell.
Owner of a lonely heart
While the findings by Poganik’s team have not yet cleared peer review, their results have already piqued the interest of their fellow heart-transplant researchers. University of Maryland surgeon Bartley Griffith—the cardiac specialist who performed the first successful transplant of a genetically modified pig heart into a human—described the study to Nature as “brilliant.”
Both Griffith and another cardiac surgeon interviewed by the journal suggested that further expansion of this research might help destigmatize the reception of older hearts as transplants, which have typically raised concerns from young heart-transplant patients. Hospitals too typically set the age limit for a viable donor heart at no older than 50, but as Poganik’s team noted, “this limit has been and continues to be raised.”
A better perception, or perhaps greater appreciation, of older hearts might certainly go a long way towards helping to meet demand. Heart transplant surgeries have risen sharply in the past decade, in part due to generally longer lifespans, with 4,636 heart transplants performed in 2024, up 81.5% since 2013.
“Most donors,” as Poganik told the site Nautilus, “are chosen because they’re young.”
