Young organs may not be a fountain of youth for recipients

Around this time last year I was attending an aging conference in Manchester, listening to a talk about fly aging, when my phone started pinging. News outlets were reporting that a hot mic had caught Russia’s and China’s leaders discussing the possibility of living forever.

“With the developments of biotechnology, human organs can be continuously transplanted, and people can live younger and younger, and even achieve immortality,” Russia’s Vladimir Putin reportedly told China’s Xi Jinping.

He seems to have been referring to the “replacement” theory of longevity, which has been supported by multiple experiments that involved physically stitching young mice to old ones. Something about the young blood rejuvenated the old mice. Perhaps young organs could rejuvenate world leaders in their 70s, too.

Unfortunately for Putin, new research pours a little cold water on this idea. Studies on transplanted hearts in both mice and humans suggest that new hearts soon adopt the biological age of the recipient, no matter how young they were to begin with. The finding could be important for transplantation, but it also highlights just how complex aging—and rejuvenation—are.

Jesse Poganik at Brigham and Women’s Hospital in Boston is one of the many scientists trying to understand exactly what it is about the bodies of young mice that rejuvenates old ones. Plenty of research has focused on seeking the secrets of youth in young blood. But what if it’s something about young organs instead?

To find out, he and his 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 another 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 transplants were different: Mice received a second heart, implanted in the neck—a procedure that’s slightly simpler and allows scientists to compare the new hearts with the existing ones. In some cases, young adult mice were given a heart from a middle-aged donor. In others, 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 in any way. These clocks were good at predicting the chronological age of mice that didn’t get new hearts.

Poganik says he was expecting to see a reciprocal effect, and that young hearts might benefit older animals, for example. In previous work by other members of his team, young mice that got old hearts experienced a buildup of senescent cells in their other organs. These cells are thought to contribute to the aging process, suggesting that receiving an old organ might prematurely age an animal.

But that’s not what he found. When he and his colleagues analyzed the transplanted hearts between four and 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. “The environment of the transplanted organ really dictates how it seems to behave biologically,” he says. The findings were published online at bioRxiv last week.

The team also looked at each mouse’s blood and other organs—including its original heart—and were surprised to find that they seemed to be unaffected by the presence of the new heart, despite the age of its donor.

The finding was backed up by data from human heart transplants. People who receive a donor heart must typically undergo a series of heart biopsies after surgery. The tiny pieces of heart tissue collected from people who had heart transplants at Brigham and Women’s have been stored for decades. And 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’s not clear why this is, but 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. Perhaps immune cells circulating in the blood might affect markers of aging in the new organ, he says.

Perhaps the potential rejuvenating effects of a young heart end up being diluted by all the other aged components of an older body, Poganik suggests. Or maybe a single organ just isn’t enough to see an effect.

Poganik hopes his finding will encourage surgeons to consider using hearts from older donors, many of which are discarded on the assumption they won’t function as well. (Machines used to preserve organs before transplantation are changing that already—and Poganik has worked on another study showing that these devices seem to rejuvenate donor livers to some extent.)

But the study also highlights just how complicated aging is. If organs seem to be getting older by one measure but not by another, how can we get a full picture of the biological age of an organ, or a person?

This complexity means that scientists are not likely to discover a true way to completely reverse aging, says Poganik. “That would mean that every aspect of aging has to go back in time,” he says. Reversing DNA damage, structural damage, and all the other degradations that are part of the aging package, across all our various cells and tissues, presents an enormous challenge.

“There are aspects of biological age that are probably reversible, and there are aspects that are probably not,” he says. Sorry, Putin.

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

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