Young organs may not be a fountain of youth for recipients

Aging is a complex process where cells and tissues gradually lose function over time. Scientists study it using tools called aging clocks, which are molecular methods to estimate the biological age of tissues or entire organisms. Biological age measures how old a body or organ feels at a cellular level, unlike chronological age, which is simply the number of years since birth. For example, a 70-year-old person might have the biological age of a 50-year-old if their cells are in good condition. In 2023, Jesse Poganik at Brigham and Women’s Hospital in Boston led research to test whether young organs could reverse aging in older recipients. The study focused on heart transplants in mice and humans, as hearts are often transplanted from younger donors to older patients.

Poganik’s team performed heart transplants in mice to observe how the age of the donor heart affects the recipient. In some cases, young adult mice received hearts from middle-aged donors, while in others, middle-aged mice got young hearts. The procedure involved implanting a second heart in the neck, which allowed scientists to compare the new heart with the original one. After 4 to 6 months, the researchers used aging clocks to assess the biological age of the transplanted hearts. Surprisingly, they found that the new hearts adopted the biological age of the recipient, regardless of the donor’s age. For instance, a young heart in an older mouse became biologically older, while an old heart in a young mouse became biologically younger. This suggests that the recipient’s body environment influences the aging process of the transplanted organ.

To validate the mouse findings, the researchers analyzed biological samples from human heart transplant patients at Brigham and Women’s Hospital. These samples, stored for decades, included tiny pieces of heart tissue collected during biopsies after surgery. Using aging clocks, the team discovered a similar pattern: the donor heart quickly adopted the biological age of the recipient, irrespective of the donor’s original age. For example, a 30-year-old heart transplanted into a 70-year-old patient would show the biological age of a 70-year-old within a short time. This challenges the idea that young organs could rejuvenate older recipients, as previously suggested by experiments where old mice were stitched to young ones, showing temporary rejuvenation effects.

The study does not fully explain why transplanted hearts adopt the biological age of the recipient. João Pedro de Magalhães, an aging researcher at the University of Birmingham who was not involved in the study, suggests the recipient’s immune system might play a role. Immune cells circulating in the blood could influence aging markers in the new organ. Alternatively, the rejuvenating effects of a young heart might be diluted by other aged components in an older body. Poganik also speculates that a single organ transplant may not be enough to reverse aging effects. The research highlights the complexity of aging, as organs may appear to age or rejuvenate by one measure but not by another, making it difficult to fully understand biological age.

Poganik’s findings could have practical implications for organ transplantation. Currently, hearts from older donors are often discarded under the assumption that they won’t function as well as younger hearts. However, the study suggests that the age of the donor heart may not significantly impact its long-term performance in the recipient. Machines used to preserve organs before transplantation might also help rejuvenate them to some extent, as shown in another study by Poganik involving donor livers. This could encourage surgeons to consider using hearts from older donors, increasing the pool of available organs for patients in need.