Young organs may not be a fountain of youth for recipients
Young organs may not be a fountain of youth for recipients
年轻器官或许并非受体返老还童的“青春之泉”
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.
执行摘要 大约在去年这个时候，我正在曼彻斯特参加一场关于衰老研究的会议，听着一场关于果蝇衰老的讲座，手机突然响个不停。新闻媒体报道称，一段意外录下的音频捕捉到了俄罗斯和中国领导人讨论永生可能性的对话。据报道，俄罗斯总统弗拉基米尔·普京对中国国家主席习近平表示：“随着生物技术的发展，人体器官可以不断移植，人们可以活得越来越年轻，甚至实现永生。”他似乎指的是长寿的“替换”理论，该理论已得到多项实验的支持，这些实验涉及将年轻小鼠与年老小鼠进行物理缝合。年轻血液中的某些成分让年老小鼠恢复了活力。或许，年轻的器官也能让七十多岁的世界领导人重焕青春。
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.
对于普京来说不幸的是，一项新的研究给这个想法泼了一盆冷水。针对小鼠和人类心脏移植的研究表明，无论捐赠的心脏最初有多年轻，移植后的心脏很快就会“同步”受体的生物学年龄。这一发现对移植医学可能具有重要意义，但也凸显了衰老——以及返老还童——是多么复杂。
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.)
波士顿布列根和妇女医院的杰西·波加尼克（Jesse Poganik）是众多试图探究年轻小鼠身体究竟有何特质能让年老小鼠恢复活力的科学家之一。大量的研究集中在从年轻血液中寻找青春的秘密。但如果秘密在于年轻的器官呢？为了找出答案，他和同事们进行了一系列小鼠心脏移植实验。在人类中，心脏移植通常涉及移除受损的心脏，并替换为通常比受体年轻得多的捐赠者的心脏。（当波加尼克评估医院记录时，他发现大多数受体比捐赠者年长约 20 岁。）
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.
小鼠移植实验有所不同：小鼠被植入了一颗位于颈部的“第二心脏”——这种手术稍微简单一些，且允许科学家将新心脏与原有心脏进行对比。在某些情况下，年轻成年小鼠被植入了中年捐赠者的心脏；而在另一些情况下，中年小鼠则获得了年轻的心脏。研究团队使用了三种“衰老时钟”（用于评估组织和整个生物体生物学年龄的分子工具），来评估这些额外的心脏是否对小鼠产生了任何影响。这些时钟在预测未接受心脏移植的小鼠的实际年龄方面表现良好。
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.
波加尼克表示，他原本预期会看到一种相互作用，例如年轻的心脏可能会让年老的动物受益。在他团队其他成员之前的研究中，接受了年老心脏的年轻小鼠，其其他器官中出现了衰老细胞的堆积。这些细胞被认为会加速衰老过程，这表明接受一个年老的器官可能会使动物过早衰老。但他的发现并非如此。当他和同事在术后四到六个月分析移植的心脏时，他们发现这些心脏似乎已经采用了受体的生物学年龄。年轻的心脏变老了，而年老的心脏变年轻了。“移植器官所处的环境确实决定了它在生物学上的表现，”他说。这些研究结果已于上周在线发表在 bioRxiv 上。
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.
研究团队还观察了每只小鼠的血液和其他器官（包括其原始心脏），惊讶地发现它们似乎并未受到新心脏存在的影响，无论捐赠者的年龄如何。这一发现得到了人类心脏移植数据的支持。接受捐赠心脏的人通常在术后必须进行一系列的心脏活检。布列根和妇女医院收集的移植患者的心脏组织样本已被保存了数十年。当波加尼克和他的同事用衰老时钟测试这些样本的生物学年龄时，他们发现了类似的模式：无论捐赠者年龄多大，新心脏都会迅速采用受体的生物学年龄。
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.
目前尚不清楚原因，但英国伯明翰大学研究衰老的若昂·佩德罗·德·马加良斯（João Pedro de Magalhães，未参与此项研究）认为，这可能与受体的免疫系统有关。他说，也许在血液中循环的免疫细胞会影响新器官中的衰老标志物。波加尼克则建议，也许年轻心脏潜在的“返老还童”效应，最终被年老身体中所有其他衰老的成分稀释了。又或者，仅仅一个器官不足以产生明显的效果。
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?
波加尼克希望他的发现能鼓励外科医生考虑使用年长捐赠者的心脏，因为许多此类心脏因被认为功能不佳而被丢弃。（用于移植前器官保存的机器已经在改变这一现状——波加尼克参与的另一项研究显示，这些设备似乎能在一定程度上让捐赠的肝脏恢复活力。）但这项研究也凸显了衰老是多么复杂。如果器官通过一种测量方式显示在变老，而通过另一种方式却不然，我们该如何全面了解一个器官或一个人的生物学年龄呢？
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.
这种复杂性意味着科学家不太可能发现一种真正能完全逆转衰老的方法，波加尼克说。“这意味着衰老的每一个方面都必须倒流，”他说。逆转 DNA 损伤、结构损伤以及衰老过程中伴随的所有其他退化，并覆盖我们所有的细胞和组织，是一个巨大的挑战。“生物学年龄的某些方面可能是可逆的，而有些方面可能并非如此，”他说。抱歉了，普京。
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.
本文首发于《麻省理工科技评论》每周生物技术通讯 The Checkup。如需每周四在收件箱中接收此类文章，请点击此处订阅。