젊은 생쥐를 늙은 생쥐에 연결하는 '이식 회춘' 이론과 달리, 새 연구에 따르면 이식된 심장은 오히려 수술자의 생물학적 나이에 맞춰진다. 마우스와 인간 심장 이식 데이터 모두에서 젊은 심장은 늙고, 늙은 심장은 젊어지는 결과가 나타났다. 이는 노화와 회춘의 메커니즘이 장기 자체보다 수용 환경에 의해 결정될 수 있음을 시사한다.
번역된 본문
요약: 작년 이맘때 나는 맨체스터에서 열린 노화 학회에서 파리 노화에 관한 강연을 듣고 있는데 휴대폰이 울리기 시작했다. 언론들이 러시아와 중국 지도자들이 영생의 가능성에 대해 논의하는 것을 핫 마이크가 포착했다고 보도했던 것이다. 러시아의 블라디미르 푸틴이 중국의 시진핑에게 "생명공학의 발전으로 인간 장기를 계속 이식할 수 있고, 사람들이 점점 더 젊어지며 심지어 불멸을 달성할 수 있다"고 말했다고 전해졌다. 그는 젊은 생쥐를 늙은 생쥐에 물리적으로 꿰매는 여러 실험에서 뒷받침된 '교체' 장수 이론을 언급한 듯하다. 젊은 피 속의 무언가가 늙은 생쥐를 회춘시켰다. 어쩌면 젊은 장기가 70대 세계 지도자들도 회춘시킬 수 있을지 모른다. 불행히도 푸틴에게는 새로운 연구가 이런 생각에 찬물을 끼얹는다. 생쥐와 인간 모두에서 이식 심장에 관한 연구는 아무리 젊은 심장이라도 이식 후 곧 수혜자의 생물학적 나이를 따르게 된다는 것을 시사한다. 이 발견은 이식 분야에서 중요할 수 있으며, 동시에 노화와 회춘이 얼마나 복잡한지를 보여준다. 보스턴 브리검 여성 병원의 제시 포가닉은 젊은 생쥐의 몸속에서 늙은 생쥐를 회춘시키는 정확한 요인이 무엇인지 이해하려는 많은 과학자 중 한 명이다. 많은 연구가 젊은 피 속에서 젊음의 비밀을 찾는 데 집중해왔다. 하지만 만약 젊은 장기 자체의 특성이라면 어떨까? 이를 알아보기 위해 그와 동료들은 생쥐에서 일련의 심장 이식을 수행했다. 인간의 심장 이식은 보통 손상되거나 부상당한 심장을 제거하고, 수혜자보다 훨씬 젊은 공여자의 심장으로 대체하는 것을 포함한다. (포가닉이 병원 기록을 조사했을 때, 대부분의 수혜자는 공여자보다 약 20세 더 많았다.) 생쥐 이식은 달랐다: 생쥐들은 목에 이식된 두 번째 심장을 받았는데, 이는 다소 더 간단한 절차이며 과학자들이 새 심장과 기존 심장을 비교할 수 있게 해준다. 일부 경우에는 젊은 성체 생쥐에게 중년 공여자의 심장이 주어졌다. 다른 경우에는 중년 생쥐가 젊은 심장을 받았다. 연구팀은 세 가지 '노화 시계'(aging clock)—조직과 개체 전체의 생물학적 나이를 추정하는 데 사용되는 분자 도구—를 사용해 추가된 심장이 생쥐에게 어떤 영향을 미치는지 평가했다. 이 시계들은 새 심장을 받지 않은 생쥐의 실제 나이를 잘 예측했다. 포가닉은 상호 효과, 즉 젊은 심장이 늙은 동물에게 이익을 줄 수 있다는 결과를 기대했다고 말한다. 그의 팀 다른 구성원들의 이전 연구에서, 늙은 심장을 받은 젊은 생쥐는 다른 장기에서 노화 세포(senescent cell)의 축적을 경험했다. 이 세포들은 노화 과정에 기여하는 것으로 여겨지며, 이는 늙은 장기를 받으면 동물이 조기 노화될 수 있음을 시사한다. 하지만 그가 발견한 것은 그것이 아니었다. 그와 동료들이 수술 후 4~6개월 사이에 이식 심장을 분석했을 때, 심장이 수혜자의 생물학적 나이를 따르는 것처럼 보였다. 젊은 심장은 늙어지고, 늙은 심장은 젊어졌다. "이식된 장기의 환경이 그것의 생물학적 거동을 실제로 결정한다"고 그는 말한다. 이 연구 결과는 지난주 bioRxiv에 온라인으로 게재되었다. 연구팀은 또한 각 생쥐의 혈액과 다른 장기—원래의 심장 포함—를 조사했고, 공여자의 나이에 상관없이 새 심장의 존재에 영향을 받지 않는 것처럼 보이는 것을 발견하고 놀랐다. 이 발견은 인간 심장 이식 데이터로도 뒷받침되었다. 공여자 심장을 받은 사람들은 수술 후 일련의 심장 생검을 받아야 한다. 브리검 여성 병원에서 심장 이식을 받은 사람들에게서 채취한 작은 심장 조각들은 수십 년 동안 보관되어 왔다. 포가닉과 동료들이 노화 시계로 이들의 생물학적 나이를 측정했을 때 비슷한 패턴을 발견했다: 공여자의 나이에 상관없이, 새 심장은 수혜자의 나이를 따르는 것이었다.
EXECUTIVE SUMMARY 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 . Deep Dive Biotechnology and health A startup claims it’s found a drug to make your blood young Generation Lab claims its drug combo can “stop the spread of aging” around the body. And it’s looking for influencers to give it a try. By Antonio Regalado archive page Montana’s plan to become an experimental medical hub just pushed forward The state’s effort to expand the “right to try” is making headway, and the first drugs are about to be reviewed. By Jessica Hamzelou archive page This geneticist’s age-reversal tech could help restore sight Yuancheng (Ryan) Lu is behind one of the buzziest results in rejuvenation science. By Antonio Regalado archive page Scientists just created female clones of male mice The sex reversal technique could be used to help rescue endangered species, say the researchers behind the work. By Jessica Hamzelou archive page Stay connected Illustration by Rose Wong Get the latest updates from MIT Technology Review Discover special offers, top stories, upcoming events, and more. Enter your email Privacy Policy Thank you for submitting your email! Explore more newsletters It looks like something went wrong. We’re having trouble saving your preferences. Try refreshing this page and updating them one more time. If you continue to get this message, reach out to us at customer-service@technologyreview.com with a list of newsletters you’d like to receive.