Transplanted hearts assimilate the recipient's biological age
- 1Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Abstract
Background. Despite the growing demand for transplantation, a shortage of donor organs persists, limiting access to this lifesaving procedure. To meet the increasing demand, organs are frequently transplanted across an age discrepancy between donor and recipients. Methods. We delineated biological age dynamics in heterochronic heart transplants performed in both mice and patients. We carried out multiomic profiling and applied advanced biomarkers of aging to understand the interactions between the transplanted organ and the host. Results. We show that the biological age of experimental heart transplants rapidly assimilates the age of recipients. Interestingly, this effect was limited to the grafted tissue without reciprocal effects on systemic biological age of the recipient. These effects were confirmed at the level of DNA methylation and gene expression. Extending our findings clinically using both omics and functional analyses, we show that the biological age of heterochronically transplanted hearts is strongly associated with the age of the recipient, rather than the donor, confirming the clinical relevance of our experimental findings. Conclusions. These data identify the systemic environment as a driving force on tissue biological age. The rejuvenation of older organs in young recipients suggests novel approaches to organ allocation that may expand the pool of transplantable organs.
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BibTeX
@misc{poganik2026transplanted,
title = {{Transplanted hearts assimilate the recipient's biological age}},
author = {J. R. Poganik and T. Matsunaga and A. Tyshkovskiy and A. Lu and A. Haghani and H. Zhou and F. Martin and S. Horvath and M. M. Givertz and S. G. Tullius and V. N. Gladyshev},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751836},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751836v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Transplanted hearts assimilate the recipient's biological age
AU - J. R. Poganik
AU - T. Matsunaga
AU - A. Tyshkovskiy
AU - A. Lu
AU - A. Haghani
AU - H. Zhou
AU - F. Martin
AU - S. Horvath
AU - M. M. Givertz
AU - S. G. Tullius
AU - V. N. Gladyshev
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751836
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751836v1
AB - Background. Despite the growing demand for transplantation, a shortage of donor organs persists, limiting access to this lifesaving procedure. To meet the increasing demand, organs are frequently transplanted across an age discrepancy between donor and recipients. Methods. We delineated biological age dynamics in heterochronic heart transplants performed in both mice and patients. We carried out multiomic profiling and applied advanced biomarkers of aging to understand the interactions between the transplanted organ and the host. Results. We show that the biological age of experimental heart transplants rapidly assimilates the age of recipients. Interestingly, this effect was limited to the grafted tissue without reciprocal effects on systemic biological age of the recipient. These effects were confirmed at the level of DNA methylation and gene expression. Extending our findings clinically using both omics and functional analyses, we show that the biological age of heterochronically transplanted hearts is strongly associated with the age of the recipient, rather than the donor, confirming the clinical relevance of our experimental findings. Conclusions. These data identify the systemic environment as a driving force on tissue biological age. The rejuvenation of older organs in young recipients suggests novel approaches to organ allocation that may expand the pool of transplantable organs.
ER -