Donor Hearts Adopt Recipients' Biological Age, Study Finds

The work was led by Jesse Poganik of Brigham and Women's Hospital in Boston and posted online at bioRxiv last week. It is relevant to a long-running debate over whether young biological material can slow or reverse aging. News reports last year described a hot mic catching Russian President Vladimir Putin telling Chinese leader Xi Jinping that biotechnology could allow continuous organ transplants and even immortality. The new findings pour cold water on that replacement theory of longevity, which had been supported by experiments stitching young mice to old ones.

Poganik and colleagues performed a set of heart transplants in mice. In humans, heart transplants typically involve removing a damaged or injured heart and replacing it with one from a donor who is usually much younger than the recipient. When Poganik assessed hospital records, he found that most recipients were about 20 years older than their donors. The mouse procedure was different: mice received a second heart implanted in the neck, a slightly simpler operation that allowed scientists to compare the new heart with the existing one. Some young adult mice were given a heart from a middle-aged donor; in other cases, middle-aged mice got young hearts.

The team used a trio of aging clocks, molecular tools used to estimate the biological ages of tissues and whole organisms, to assess whether the additional hearts affected the mice. These clocks were good at predicting the chronological age of mice that did not get new hearts. Poganik had expected to see a reciprocal effect, such as young hearts benefiting older animals. Previous work by other members of his team had found that young mice given old hearts experienced a buildup of senescent cells in their other organs. Those cells are thought to contribute to aging, suggesting that receiving an old organ might prematurely age an animal.

But when Poganik and his colleagues analyzed the transplanted hearts four to six months after surgery, they found that the hearts seemed to have adopted the biological age of the recipients. Young hearts got older, and old hearts got younger. Poganik says the environment of the transplanted organ really dictates how it seems to behave biologically. The team also looked at each mouse's blood and other organs, including its original heart, and was surprised to find that they seemed unaffected by the presence of the new heart, despite the age of its donor.

Data from human heart transplants backed up the mouse finding. People who receive a donor heart must typically undergo a series of heart biopsies after surgery. Tiny pieces of heart tissue collected from people who had heart transplants at Brigham and Women's have been stored for decades. When Poganik and his colleagues tested their biological ages with the aging clocks, they found a similar pattern: no matter the age of the donor, a new heart quickly adopts the biological age of the person who received it.

It is not clear why this happens. João Pedro de Magalhães, who studies aging at the University of Birmingham in the UK and was not involved in the study, thinks it might have something to do with the recipient's immune system. Immune cells circulating in the blood might affect markers of aging in the new organ, he says. Poganik suggests the potential rejuvenating effects of a young heart may be diluted by all the other aged components of an older body, or that a single organ may simply not be enough to produce an effect.

Poganik hopes the finding will encourage surgeons to consider using hearts from older donors, many of which are discarded on the assumption that they will not function as well. Machines used to preserve organs before transplantation are already changing that, and Poganik has worked on another study showing that these devices seem to rejuvenate donor livers to some extent. The study also highlights how complicated aging and rejuvenation are.

Editor's Summary The study found that transplanted hearts in mice and humans adopt the biological age of their recipients, with young hearts becoming older and old hearts becoming younger. The result challenges the idea that young organs can rejuvenate older recipients and may encourage use of older donor hearts. It also underscores that aging and rejuvenation involve complex interactions between an organ and its host.