Hundreds of people die each year while waiting for the right organ for a high-stakes transplant. This is the kind of resource shortage that has led to bold alternatives, including artificial hearts and animal-to-human “xenotransplantation” experiments. But if both of these options leave you a little squeamish, how would you feel about receiving a replacement human heart with a slight age gap?
Long story short, this could work surprisingly well. Harvard biochemistry researcher Jesse Poganik and his collaborators in Boston discovered something peculiar in animal experiments that led them to delve deeper into 11 human heart transplant cases where there was a significant age disparity between donor and recipient. Working with biopsy samples from these transplant patients, Poganik’s lab performed DNA methylation tests, measurements of aging at the cellular level.
The results matched their animal tests. It sounds like a Hallmark movie, but the older hearts started looking and acting like the younger ones they were paired with, and the younger hearts started looking and acting more like old souls.
Poganik’s lab also triple-checked this data against the electronic medical records of hundreds of other heart transplant recipients, finding that parameters such as heart rate, exercise endurance, and the thickness of the heart’s posterior wall more closely resembled the recipient’s age than the donor’s.
“What’s remarkable is that we saw exactly the same effects as in mice,” Poganik told the journal Nature. “Some, but not all, functional measures followed the prediction that these older hearts in younger individuals functioned as if they were biologically younger, and vice versa.”
Without wasting a moment
As Poganik and co-authors noted in their study, now available 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 approximately 8 to 24 years for older hearts surgically inserted into younger patients and 38 to 50 years for younger hearts transplanted into older patients – gaps spanning decades that these new hearts were able to overcome.
Poganik’s team, which focuses on the science of aging (perhaps obviously hoping to reverse it), said there are already promising candidates to explain the unusual behavior of these transplants. The team conducted extensive analyzes of each heart’s available RNA and the so-called transcriptomic pathways by which this RNA regulates physiological processes, finding the most significant changes in genes related to mitochondria and the heart’s energy metabolism.
“Additional work has shown that old organ transplantation also promotes senescence (aging) in recipient tissues … including mitochondrial DNA, consistent with mitochondria being a central node in age-related graft-recipient crosstalk,” the team noted.
In other words, there is promising data here to identify which parts of the body contribute most to aging. And it seems to be the mitochondria, the famous powerhouse of the cell.
Owner of a lonely heart
Although Poganik’s team’s results have not yet been peer-reviewed, their results have already sparked the interest of fellow heart transplant researchers. University of Maryland surgeon Bartley Griffith, the cardiologist who performed the first successful transplant of a genetically modified pig heart into a human, called the study “brilliant.”
Griffith and another heart surgeon interviewed by the journal suggested that further expansion of this research could help destigmatize receiving older hearts as transplants, which typically raises concerns among younger heart transplant patients. Hospitals also typically set the age limit for a viable heart donor at no more than 50, but as Poganik’s team noted, “this limit has been and continues to be raised.”
A better perception, or perhaps a greater appreciation, of older hearts could certainly go a long way in meeting demand. Heart transplant operations have increased sharply over the past decade, partly due to generally longer lifespans, with 4,636 heart transplants performed in 2024, an increase of 81.5% since 2013.
“Most donors,” as Poganik explained to the Nautilus website, “are chosen because they are young.”
Gn Health
