Preprint links the biological age of the heart to the recipient's age — ScienceAlert
In a preprint that has not yet undergone peer review, researchers led by Harvard Medical School molecular biologist Jesse Poganik found that the biological age of a transplanted heart may change in accordance with the age of the recipient's body. Older hearts in younger bodies showed signs of biological rejuvenation, while younger hearts in older bodies showed accelerated aging, ScienceAlert reports.
Experiments in mice
First, the scientists performed transplants between mice of different ages. In this model, recipients retained their own heart, while the donor organ was connected to blood vessels in the neck area. This allowed the animals to survive and made it possible to track how the new environment affected the transplanted organ.
After four to six months, the team analyzed DNA methylation in the transplanted and native hearts of the mice, as well as in the liver and blood. Such epigenetic markers are used to assess biological age. Transplanted old hearts in young mice showed signs of rejuvenation, while young hearts in older animals appeared biologically older. At the same time, the age of the donor heart had almost no effect on the biological age of the recipients' native heart, liver, or blood.
Data on heart recipients
The authors also examined archived heart tissue samples from 11 people after transplantation. The difference between donor and recipient age in this group ranged from cases where the recipient was 24 years younger than the donor to cases where the recipient was 50 years older.
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DNA methylation analysis showed that the biological age of transplanted hearts was more closely linked to the age of recipients than to that of donors. The researchers also studied medical data from hundreds of patients one year after transplantation. Certain structural and functional characteristics of transplanted hearts correlated with recipients' age. The most pronounced relationship concerned physical exertion: functional capacity and peak oxygen consumption declined as recipient age increased, regardless of the donor organ's age.
Further research is needed
The small sample size of people does not allow definitive conclusions about the clinical implications. In particular, the study does not establish whether the identified biological rejuvenation of an older heart is associated with better long-term outcomes for patients.
The scientists suggest that these data may influence approaches to evaluating donor organs in the future, as younger hearts are currently usually preferred for transplantation. The possible mechanism of the changes has not yet been clarified, but in mice the researchers recorded notable changes in the activity of genes associated with mitochondrial and metabolic processes.
