人类为什么需要睡眠？
Goodnight. Sleep Clean.

SLEEP seems like a perfectly fine waste of time. Why would our bodies evolve to spend close to one-third of our lives completely out of it, when we could instead be doing something useful or exciting? Something that would, as an added bonus, be less likely to get us killed back when we were sleeping on the savanna?

睡眠，从表面看来它完全是在浪费我们的宝贵时间。为什么我们的身体要演化出这么一种奇怪的机制？为什么我们会放任人生近三分之一的时间就这么白白流逝掉，却不用它来从事些有益或者好玩的事情？想当年——当我们的祖先还生活在热带亚热带稀树草原上的远古时代，睡眠无疑大大增加了丧命的危险，但为什么——为什么睡眠对我们来说如此必不可少？

“Sleep is such a dangerous thing to do, when you’re out in the wild,” Maiken Nedergaard, a Danish biologist who has been leading research into sleep function at the University of Rochester’s medical school, told me. “It has to have a basic evolutional function. Otherwise it would have been eliminated.”

“当你露宿野外时，呼呼大睡实在太过危险，”美国罗切斯特医学院(Rochester’s medical school)睡眠功能研究的领导人，丹麦生物学家麦肯·尼德佳德(Maiken Nedergaard)告诉我。“睡眠必定有其演化意义上的基本功能，否则它绝不可能在自然选择下存留至今。”

We’ve known for some time that sleep is essential for forming and consolidating memories and that it plays a central role in the formation of new neuronal connections and the pruning of old ones. But that hardly seems enough to risk death-by-leopard-in-the-night. “If sleep was just to remember what you did yesterday, that wouldn’t be important enough,” Dr. Nedergaard explains.

此前我们已经获知，睡眠对于记忆的形成和巩固至关重要，它在形成新的神经连接及修整旧有神经连接的过程中发挥了核心作用。但是，冒着半夜落入豹吻的风险只为获得这么一点回报，似乎还不够划算。“假如睡眠只能帮你记住你昨天的所作所为，那么它就不会如此重要，”尼德佳德博士解释说。

In a series of new studies, published this fall in the journal Science, the Nedergaard lab may at last be shedding light on just what it is that would be important enough. Sleep, it turns out, may play a crucial role in our brain’s physiological maintenance. As your body sleeps, your brain is quite actively playing the part of mental janitor: It’s clearing out all of the junk that has accumulated as a result of your daily thinking.

在去年秋天发表于《科学》杂志(Science)上的一系列新研究中，尼德佳德实验室可能终于为解答睡眠的重要性问题找到了关键线索。原来，睡眠在大脑生理层面的“维护保养”中作用举足轻重。当你的身体陷入沉睡，你的大脑依然尽职尽责地担任着你的“精神管理员”，替你把你白天思维活动时累积起来的“垃圾”清扫得干干净净。

Recall what happens to your body during exercise. You start off full of energy, but soon enough your breathing turns uneven, your muscles tire, and your stamina runs its course. What’s happening internally is that your body isn’t able to deliver oxygen quickly enough to each muscle that needs it and instead creates needed energy anaerobically. And while that process allows you to keep on going, a side effect is the accumulation of toxic byproducts in your muscle cells. Those byproducts are cleared out by the body’s lymphatic system, allowing you to resume normal function without any permanent damage.

让我们来回顾一下体育锻炼时你的身体都会发生哪些反应：刚开始你精力充沛，但不久你的呼吸就开始不均匀，肌肉疲劳，耐力也逐渐达到极限。这说明在你体内提供氧气的速度已经无法满足所有肌肉的需要，迫使它们不得不采用厌氧方式产生能量。虽然该过程可以保证你继续运动，但它有一个副作用：有毒的副产物将在你的肌肉细胞中积累。幸而，人体拥有淋巴系统来帮你清除这些副产物，使你的身体恢复正常功能，免于遭受任何永久性损伤。

The lymphatic system serves as the body’s custodian: Whenever waste is formed, it sweeps it clean. The brain, however, is outside its reach — despite the fact that your brain uses up about 20 percent of your body’s energy. How, then, does its waste — like beta-amyloid, a protein associated with Alzheimer’s disease — get cleared? What happens to all the wrappers and leftovers that litter the room after any mental workout?

淋巴系统是人体的管理员：无论何时，只要有垃圾形成，它都能把它们打扫干净。但对于大脑，淋巴系统却鞭长莫及。大脑消耗的能量可以达到全身总耗能量的20%左右。它要如何清除β-淀粉样蛋白（一种与阿尔茨海默氏病相关的蛋白质）之类的垃圾呢？在脑力运动之后，该怎么处理积累下来的废物？

“Think about a fish tank,” says Dr. Nedergaard. “If you have a tank and no filter, the fish will eventually die. So, how do the brain cells get rid of their waste? Where is their filter?”

“让我们拿鱼缸来打个比方，”尼德佳德博士说。“假如你有一个鱼缸，可这个鱼缸上没有过滤器，所有的鱼最终都将难逃一死。那么，脑细胞要如何保护自己免受自身废弃物的损伤？它们的过滤器在哪里？”

UNTIL a few years ago, the prevailing model was based on recycling: The brain got rid of its own waste, not only beta-amyloid but other metabolites, by breaking it down and recycling it at an individual cell level. When that process eventually failed, the buildup would result in age-related cognitive decline and diseases like Alzheimer’s. That “didn’t make sense” to Dr. Nedergaard, who says that “the brain is too busy to recycle” all of its energy. Instead, she proposed a brain equivalent of the lymphatic system, a network of channels that cleared out toxins with watery cerebrospinal fluid. She called it the glymphatic system, a nod to its dependence on glial cells (the supportive cells in the brain that work largely to maintain homeostasis and protect neurons) and its function as a sort of parallel lymphatic system.

直到几年之前，以循环理论为基础的模型一直非常风行。该模型认为，大脑可以在个体细胞水平上分解β-淀粉样蛋白及其他代谢产物，并对其循环利用，从而实现“垃圾清理”。一旦该程序失灵，细胞废弃物就会积聚，进而导致年龄相关性认知功能减退、阿尔茨海默氏病等疾病。但尼德佳德博士认为这“说不通”，“大脑太过繁忙，不会有余力去循环利用”所有的能量。她提出了一套自己的假说：大脑拥有自己的“淋巴系统”，这个复杂的管道网络通过水性的脑脊液来清除毒素。她将其命名为脑部类淋巴系统(glymphatic system)。首字母“g”代表该系统依赖于神经胶质细胞（大脑中的支持细胞，其主要作用在于维持自稳态，并保护神经元），后半部分则表明其功能与淋巴系统(lymphatic system)类似。

She was hardly the first to think in those terms. “It had been proposed about one hundred years ago, but they didn’t have the tools to study it properly,” she says. Now, however, with advanced microscopes and dyeing techniques, her team discovered that the brain’s interstitial space — the fluid-filled area between tissue cells that takes up about 20 percent of the brain’s total volume — was mainly dedicated to physically removing the cells’ daily waste.

上述概念并非尼德佳德博士首创。“早在大约一百年前，人们就已经提出了这一理论，只不过当时的人们没有合适的工具来研究它，”她说。现在，在先进的显微镜和染色技术的协助下，她的研究团队发现，大脑组织间隙——位于脑组织细胞之间的充满液体的区域，约占总脑容量的20%——专门负责清除脑细胞的日常废物。

When members of Dr. Nedergaard’s team injected small fluorescent tracers into the cerebrospinal fluid of anesthetized mice, they found that the tracers quickly entered the brain — and, eventually, exited it — via specific, predictable routes.

尼德佳德博士研究团队的成员对小鼠实施了麻醉，然后将微小的荧光示踪剂注入它们的脑脊液。他们发现，这些示踪剂迅速进入了大脑，并沿着特定、可预测的路径从脑中排出。

The next step was to see how and when, exactly, the glymphatic system did its work. “We thought this cleaning process would require tremendous energy,” Dr. Nedergaard says. “And so we asked, maybe this is something we do when we’re sleeping, when the brain is really not processing information.”

下一步，研究人员探讨了glymphatic系统究竟是在何时，以及如何执行其功能。“我们认为，这一清理过程可能需要巨大的能量，”尼德佳德博士说。“于是我们进一步想问，我们会不会是在大脑不再处理任何信息时——即，入睡后，才进行这些工作的？”

In a series of new studies on mice, her team discovered exactly that: When the mouse brain is sleeping or under anesthesia, it’s busy cleaning out the waste that accumulated while it was awake.

在对小鼠进行了一系列的新研究之后，她的研究团队发现事实的确如此：当小鼠的大脑处于睡眠或麻醉状态之下时，它一直忙于清除在清醒时积累下来的那些垃圾。

In a mouse brain, the interstitial space takes up less room than it does in ours, approximately 14 percent of the total volume. Dr. Nedergaard found that when the mice slept, it swelled to over 20 percent. As a result, the cerebrospinal fluid could not only flow more freely but it could also reach further into the brain. In an awake brain, it would flow only along the brain’s surface. Indeed, the awake flow was a mere 5 percent of the sleep flow. In a sleeping brain, waste was being cleared two times faster. “We saw almost no inflow of cerebrospinal fluid into the brain when the mice were awake, but then when we anesthetized them, it started flowing. It’s such a big difference I kept being afraid something was wrong,” says Dr. Nedergaard.

在小鼠的脑部，组织间隙约占总脑容量的14%，比我们脑中所占的比例要小。但尼德佳德博士发现，当小鼠入睡后，组织间隙的体积可膨胀至总脑容量的20%以上。这不仅使脑脊液得以更自由地流动，还使其可以达到脑部更深的部位。在清醒的脑中，脑脊液只能沿着大脑表面流动。确切说来，清醒时的脑脊液流量仅为睡眠时的5%，而睡眠时大脑清除废物的速度可达清醒时的2倍。“在小鼠清醒时，我们几乎观察不到有脑脊液流入大脑；但小鼠被麻醉后，脑脊液就开始流动。其间的差异如此之大，害我一直担心是不是有什么事情不对劲，“尼德佳德博士说。

Similar work in humans is still in the future. Dr. Nedergaard is currently awaiting board approval to begin the equivalent study in adult brains in collaboration with the anesthesiologist Helene Benveniste at Stony Brook University.

类似的人体研究仍有待未来实现。尼德佳德博士正期待着董事会的批准——她希望能有机会与石溪大学(Stony Brook University)的麻醉学家海伦妮·本维尼斯特(Helene Benveniste)合作，共同对成年人的大脑进行同类研究。

So far the glymphatic system has been identified as the neural housekeeper in baboons, dogs and goats. “If anything,” Dr. Nedergaard says, “it’s more needed in a bigger brain.”

迄今为止，人们发现在狒狒、狗和山羊等动物中，都有glymphatic系统在发挥“神经管家”的功能。“脑容量越大，”尼德佳德博士说，“应该就越需要这么一个系统。”

MODERN society is increasingly ill equipped to provide our brains with the requisite cleaning time. The figures are stark. Some 80 percent of working adults suffer to some extent from sleep deprivation. According to the National Sleep Foundation, adults should sleep seven to nine hours. On average, we’re getting one to two hours less sleep a night than we did 50 to 100 years ago and 38 minutes less on weeknights than we did as little as 10 years ago. Between 50 and 70 million people in the United States suffer from some form of chronic sleep disorder. When our sleep is disturbed, whatever the cause, our cleaning system breaks down. At the University of Pennsylvania’s Center for Sleep and Circadian Neurobiology, Sigrid Veasey has been focusing on precisely how restless nights disturb the brain’s normal metabolism. What happens to our cognitive function when the trash piles up?

现代社会越来越无力保证我们的大脑进行这些清理工作所必需的时间。以下数字无不昭示着这一严峻事实：约80%的成年职业劳动者遭受着一定程度的睡眠剥夺。全美睡眠基金会(National Sleep Foundation)指出，成年人每天应睡眠七至九小时。平均而言，当今人们每夜的睡眠时间较之50到100年前少了一至两个小时，工作日之夜的睡眠时间比10年前还要短38分钟。在美国，约有5000至7000万人受到某种形式的慢性睡眠障碍的困扰。无论出于何种原因，只要睡眠受到了干扰，我们的清理系统就会失灵。宾夕法尼亚大学(University of Pennsylvania)睡眠与节律神经生物学中心(Center for Sleep and Circadian Neurobiology)的西格丽德·维齐(Sigrid Veasey)一直在潜心钻研彻夜难眠是如何扰乱脑部的正常代谢的。当脑部垃圾堆积如山时，我们的认知功能又会受到怎样的影响？

At the extreme end, the result could be the acceleration of neurodegenerative diseases like Alzheimer’s and Parkinson’s. While we don’t know whether sleep loss causes the disease, or the disease itself leads to sleep loss — what Dr. Veasey calls a “classic chicken-and-egg” problem — we do know that the two are closely connected. Along with the sleep disturbances that characterize neurodegenerative diseases, there is a buildup of the types of proteins that the glymphatic system normally clears out during regular sleep, like beta-amyloids and tau, both associated with Alzheimer’s and other types of dementia.

在最极端的情况下，它可能导致阿尔茨海默氏病、帕金森氏病等神经退行性疾病病程的加速。虽然我们还不知道到底是睡眠不足导致了这些疾病，还是这些疾病本身导致了睡眠不足——维齐博士称其为“先有鸡还是先有蛋的经典问题”——但我们明确可知的是，这两者密切相关。随着神经退行性疾病特征性的睡眠障碍的持续，往常依赖于glymphatic系统在正常睡眠期间清除的几种蛋白质，如β-淀粉样蛋白和tau蛋白等在脑部堆积，而上述两种蛋白均与阿尔茨海默氏病和其他多种痴呆症相关。

“To me,” says Dr. Veasey, “that’s the most compelling part of the Nedergaard research. That the clearance for these is dramatically reduced from prolonged wakefulness.” If we don’t sleep well, we may be allowing the very things that cause neural degeneration to pile up unchecked.

“对我来说，”维齐博士说，“尼德佳德的研究中最引人注目的就是这一点：清醒时间的延长导致大脑清理垃圾的能力显著降低。”如果我们睡不好，就等于坐视这些可导致神经变性的垃圾继续堆积。

Even at the relatively more benign end — the all-nighter or the extra-stressful week when you caught only a few hours a night — sleep deprivation, as everyone who has experienced it knows, impedes our ability to concentrate, to pay attention to our environment and to analyze information creatively. “When we’re sleep-deprived, we can’t integrate or put together facts,” as Dr. Veasey puts it.

即使是在相对不那么严重的情况下——譬如这一周你的工作压力特别大，你不得不开夜车或者每晚只能眯上几个小时，睡眠剥夺仍然会影响你的集中力，使你无法用心注意周围的环境，并阻碍你有创造性地对信息进行分析——只要经历过的人都会对此深有体会。“当我们遭受睡眠剥夺时，就无法有效地将事实的片段整合在一起，”维齐博士如是说。

But there is a difference between the kind of fleeting sleep loss we sometimes experience and the chronic deprivation that comes from shift work, insomnia and the like. In one set of studies, soon to be published in The Journal of Neuroscience, the Veasey lab found that while our brains can recover quite readily from short-term sleep loss, chronic prolonged wakefulness and sleep disruption stresses the brain’s metabolism. The result is the degeneration of key neurons involved in alertness and proper cortical function and a buildup of proteins associated with aging and neural degeneration.

然而，在偶尔的睡眠不足与因倒班工作或失眠等原因导致的慢性睡眠剥夺之间存在着根本性的差异。在不久后将发表于《神经科学杂志》(The Journal of Neuroscience)上的一组研究中，维齐实验室发现，虽然我们的大脑可以从短期的睡眠不足中迅速恢复，但慢性、长期的失眠和睡眠紊乱会对大脑的新陈代谢造成强烈的应激压力。结果导致与警觉和正常皮层功能有关的关键神经元发生变性，与衰老和神经变性相关的蛋白质不断积累。

It’s like the difference between a snowstorm’s disrupting a single day of trash pickup and a prolonged strike. No longer quite as easy to fix, and even when the strike is over, there’s likely to be some stray debris floating around for quite some time yet. “Recovery from sleep loss is slower than we’d thought,” Dr. Veasey notes. “We used to think that after a bit of recovery sleep, you should be fine. But this work shows you’re not.”

这就像是偶尔有一天暴风雪干扰了垃圾清扫工作与清洁工长期罢工之间的区别。后者可没那么容易解决，即使罢工结束了，垃圾碎屑漫天飞的状况却可能在相当长的一段时间内继续持续。“从睡眠不足中恢复的过程比我们想象的要慢，”维齐博士指出。“我们曾经以为，只要经过一点补眠，一切就会回复正轨。但这项研究告诉我们事实并非如此。”

If you put her own research together with the findings from the Nedergaard lab, Dr. Veasey says, it “very clearly shows that there’s impaired clearance in the awake brain. We’re really starting to realize that when we skip sleep, we may be doing irreparable damage to the brain, prematurely aging it or setting it up for heightened vulnerability to other insults.”

维齐博士表示，如果你把她的研究与尼德佳德实验室的研究结果结合起来看，你就会发现，“很显然，在清醒的大脑中，组织间隙的清理功能无法正常进行。我们这才开始意识到，不好好睡觉就等于是在对大脑施加不可挽回的损害，使其过早衰老或者格外容易受到其他伤害。”

In a society that is not only chronically sleep-deprived but also rapidly aging, that’s bad news. “It’s unlikely that poor sleep as a child would actually cause Alzheimer’s or Parkinson’s,” says Dr. Veasey, “but it’s more likely that you may shift one of those diseases by a decade or so. That has profound health and economic implications.”

在当今这个不仅人们普遍存在慢性睡眠不足，而且老龄化也在迅速加剧的社会里，这无疑是个噩耗。“虽然童年时代糟糕的睡眠未必会导致阿尔茨海默氏病或帕金森氏病，”维齐博士说，“但它很可能让这些疾病提前十年左右找上你。无论从健康和经济的角度而言，其影响均十分深远。”

It’s a pernicious cycle. We work longer hours, become more stressed, sleep less, impair our brain’s ability to clean up after all that hard work, and become even less able to sleep soundly. And if we reach for a sleeping pill to help us along? While work on the effects of sleeping aids on the glymphatic system remains to be done, the sleep researchers I spoke with agree that there’s no evidence that aided sleep is as effective as natural sleep.

这简直是一种恶性循环。当我们延长工作时间，身体的应激压力就会增大；睡眠时间减少，损害了大脑在繁重工作后自我清理的能力，结果就愈发难以熟睡。假若我们求助于安眠药的催眠魔力，情况又会如何？尽管有关辅助睡眠对glymphatic系统影响的研究还有待完成，但我所采访过的睡眠研究人员普遍认同，尚无证据表明辅助睡眠与自然睡眠同样有效。

There is, however, reason to hope. If the main function of sleep is to take out our neural trash, that insight could eventually enable a new understanding of both neurodegenerative diseases and regular, age-related cognitive decline. By developing a diagnostic test to measure how well the glymphatic system functions, we could move one step closer to predicting someone’s risk of developing conditions like Alzheimer’s or other forms of dementia: The faster the fluids clear the decks, the more effectively the brain’s metabolism is functioning.

然而，希望依然存在。如果睡眠的主要功能确实在于清理神经垃圾，该观点将启发我们从全新的视角来认识神经退行性疾病和常规的年龄相关性认知功能减退。通过开发可衡量glymphatic系统功能的诊断测试，我们距离预测个人的阿尔茨海默氏病及其他痴呆症风险这一目标就更近了一步：脑部垃圾的清理速度越快，大脑新陈代谢的运作就越有效。 “Such a test could also be used in the emergency room after traumatic brain injury,” Dr. Nedergaard says, “to see who is at risk of developing decline in cognitive function.”

“该测试也可以用于在急诊室对创伤性脑损伤进行鉴定，”尼德佳德博士说，“从而判断哪些伤患存在认知功能减退的风险。”

We can also focus on developing earlier, more effective interventions to prevent cognitive decline. One approach would be to enable individuals who suffer from sleep loss to sleep more soundly — but how? Dr. Nedergaard’s mice were able to clear their brain’s waste almost as effectively under anesthesia as under normal sleeping conditions. “That’s really fascinating,” says Dr. Veasey. Though current sleeping aids may not quite do the trick, and anesthetics are too dangerous for daily use, the results suggest that there may be better ways of improving sleep pharmacologically.

我们也可以将研究重点放在开发能更早实施，效果也更好的干预措施之上，以预防认知功能的减退。其中一种思路是：让睡眠不足的人享受到更为深沉的睡眠——只是，如何才能达成这一目标？在尼德佳德博士的研究中，麻醉小鼠清除脑部垃圾的效率几乎可与正常睡眠状态下的小鼠相当。“这真令人振奋，”维齐博士说。尽管现有的辅助睡眠可能还没有这种神奇的魔力，且日常使用麻醉剂也太过危险，但研究结果表明，或许还有更好的药理学途径能够改善睡眠。

Now that we have a better understanding of why sleep is so important, a new generation of drug makers can work to create the best possible environment for the trash pickup to occur in the first place — to make certain that our brain’s sleeping metabolism is as efficient as it can possibly be.

既然现在我们对睡眠的重要性有了更好的了解，新一代的药物制造商或应致力于从一开始就为这一垃圾清理工作创造最理想的环境，以保证大脑的睡眠代谢能够尽可能高效地进行。

A second approach would take the opposite tack, by seeking to mimic the cleanup-promoting actions of sleep in the awake brain, which could make a full night of sound sleep less necessary. To date, the brain’s metabolic process hasn’t been targeted as such by the pharmaceutical industry. There simply wasn’t enough evidence of its importance. In response to the evolving data, however, future drug interventions could focus directly on the glymphatic system, to promote the enhanced cleaning power of the sleeping brain in a brain that is fully awake. One day, scientists might be able to successfully mimic the expansion of the interstitial space that does the mental janitorial work so that we can achieve maximally efficient round-the-clock brain trash pickup.

第二种思路则采取了相反的策略：如果可以在清醒的大脑中模仿睡眠中的促清理作用，那么人也可能不再需要一整夜的熟睡。迄今为止，医药产业尚未以大脑的代谢过程为靶标进行过此类探索。这只是因为此前还没有足够的证据表明其重要性。然而，随着数据资料不断演进，未来的药物干预将得以直接着眼于glymphatic系统，促进完全清醒的大脑也产生睡眠大脑特有的强大清理能力。有朝一日，科学家们将成功地模拟出脑部组织间隙的扩张，这样我们的“精神管理员”就可以日以继夜地以最高的效率为我们清理脑部垃圾。

If that day comes, they would be on their way to discovering that all-time miracle drug: one that, in Dr. Veasey’s joking words, “could mean we never have to sleep at all.”

待到那一天到来，科学家们说不定还会更进一步，去研发更加神奇的药物：维齐博士开玩笑说，有了它，“搞不好我们再也不需要睡觉了。”

玛丽亚·康尼科娃(Maria Konnikova)是《驾驭心智：像福尔摩斯一样思考》(Mastermind: How to Think Like Sherlock Holmes)一书作者。

本文最初发表于2014年1月12日。

翻译：任扶摇