Young Organs May Not Be a Fountain of Youth for Recipients
Imagine if you could stay young forever by swapping out your old organs for new ones. That's the idea behind a popular theory of rejuvenation, and it even caught the attention of world leaders. Last year, a hot mic reportedly caught Russia's Vladimir Putin telling China's Xi Jinping that with biotechnology, human organs could be continuously transplanted, allowing people to live younger and younger—perhaps even achieving immortality. He seemed to be referring to the 'replacement' theory of longevity, which has been supported by experiments where young mice were stitched to old ones, and something about the young blood seemed to rejuvenate the old mice. But new research throws 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. This finding could be important for transplantation, but it also shows just how complex aging—and rejuvenation—really are.
Jesse Poganik at Brigham and Women's Hospital in Boston is one of many scientists trying to understand what it is about young mice that rejuvenates old ones. A lot of research has focused on young blood, but what if it's something about young organs instead? To find out, he and his colleagues performed heart transplants in mice. In humans, heart transplants usually involve replacing a damaged heart with one from a donor who is typically much younger than the recipient. (When Poganik checked 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 simpler procedure that lets scientists compare the new heart with the existing one. In some cases, young adult mice got a heart from a middle-aged donor. In others, middle-aged mice got young hearts.
The team used three 'aging clocks'—molecular tools that estimate the biological ages of tissues and organisms—to see if the extra hearts affected the mice. These clocks were good at predicting the chronological age of mice that didn't get new hearts. Poganik expected to see a reciprocal effect, like young hearts benefiting older animals. In previous work by other team members, young mice that got old hearts had a buildup of senescent cells in their other organs. These cells are thought to contribute to aging, suggesting that receiving an old organ might prematurely age an animal. But that's not what he found. When they analyzed the transplanted hearts four to six months after surgery, 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 unaffected by the new heart, despite the donor's age. The finding was backed up by data from human heart transplants. People who receive a donor heart typically undergo heart biopsies after surgery. Tiny pieces of heart tissue from people who had 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 donor's age, a new heart quickly adopts the biological age of the person who received it.
It's not clear why this happens, 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 affect markers of aging in the new organ, he says. Maybe the potential rejuvenating effects of a young heart get 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 because they're assumed to 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.) But the study also highlights how complicated aging is. If organs seem to be getting older by one measure but not another, how can we get a full picture of the biological age of an organ or a person? This complexity means 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 aging, across all our 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.