线粒体如何决定你的代谢：从 ATP、MPC 到癌症与衰老｜Huberman Lab Jared Rutter
Huberman Lab 本期与 Jared Rutter 从细胞代谢、MPC 和能量分配出发，解释线粒体如何连接 ATP、衰老、心力衰竭与癌症。
这期 Huberman Lab 不是一集“怎样提高代谢”的生活方式节目，而是一场从细胞内部重新定义代谢的基础科学访谈。Andrew Huberman 邀请犹他大学生物化学教授、Howard Hughes Medical Institute 研究员 Jared Rutter，讨论线粒体怎样把营养变成能量，怎样决定细胞是继续工作、储存资源还是制造更多自己，以及这些选择为什么会牵涉衰老、心力衰竭和癌症。节目时长约 2 小时 4 分钟，官方 show notes 提供了从线粒体起源到活性氧的完整章节。12
读者最适合带着一个问题进入这期访谈：身体的“代谢”究竟是谁在执行？ Rutter 给出的答案是，身体并不存在一个统一的代谢程序。所谓“我的代谢”，其实是大约数万亿个细胞各自处理营养、生产 ATP、合成生物量和维持自身功能的总和。线粒体也不只是教科书里那座“细胞发电厂”，它更像细胞的资源分配节点：同一份葡萄糖，既可以被氧化成 ATP，也可以被留下来制造蛋白质、膜、DNA 和新的细胞。
先记住三件事
- 代谢发生在细胞里。 食物被消化成糖、氨基酸和脂肪，进入各个细胞后，细胞会根据自身任务选择不同的化学路径。心肌细胞、肠道干细胞、神经元和脂肪细胞面对同一顿饭，做出的代谢选择并不相同。
- 线粒体同时参与供能和建造。 线粒体可以帮助细胞把丙酮酸送入氧化通路，生成 ATP；它也参与决定营养是否被转成新的细胞材料。细胞的关键选择经常是“燃烧现有资源”还是“用资源建造更多东西”。
- 疾病可能是资源分配出了问题。 节目中最有解释力的动物实验是心脏特异性去除 MPC：小鼠仍能用脂肪供能，却把更多葡萄糖导向细胞生长，最后形成扩大的心脏并死于心力衰竭。这个例子说明，细胞有能量并不等于细胞把能量用在了正确的地方。
代谢不是一个总开关
日常语言里的“代谢”常常等同于卡路里进出、基础代谢率或体重变化。Rutter 把镜头拉近到细胞：人体摄入食物、饮水和氧气后，消化系统把它们拆成较小的分子；这些分子进入不同组织和细胞，在细胞内部被重新加工，最后形成能量、细胞材料和废物。身体层面的代谢，就是这些细胞过程叠加后的结果。1
这个视角改变了“代谢快慢”的提问方式。心肌细胞的核心任务是持续收缩，因此它的线粒体被配置成稳定提取燃料、制造 ATP。肠道干细胞承担的是更新肠壁，肠道内层大约每 5 到 7 天更新一次；这类细胞更需要复制 DNA、蛋白质、膜和脂质，代谢程序就会偏向制造
biomass，也就是构成新细胞的生物量。神经元的长突起需要在远离细胞体的地方释放神经递质，线粒体会沿着突起移动，把 ATP 在局部生产出来。Rutter 还提到，Craig Thompson 在 Sloan Kettering 的研究提示：一个细胞里甚至可能同时存在两类功能不同的线粒体。一类更偏向生物合成，另一类更偏向提取能量和生产 ATP。这个说法是对复杂现象的简化，但它足以提醒读者，线粒体不是每个细胞里完全相同的一批“电池”。2
线粒体为什么像外来的细胞
线粒体的特殊性从它的演化史开始。Rutter 采用的主流解释是“内共生”（endosymbiosis）：一个自由生活的细菌被另一个细胞吞入，随后双方形成稳定合作，最终成为复杂细胞的一部分。植物、动物和真菌都属于这种复杂细胞演化出的生命形式。线粒体保留了一个环形的独立基因组，被认为是细菌祖先留下的遗迹；细胞核里的基因组则以线性染色体存在。1
这个背景也解释了线粒体疾病的母系遗传特点。受精时，精子的细胞核进入卵子，但精子的细胞质通常不会作为胚胎细胞质的主要来源进入下一代。因此，一个人的线粒体 DNA 基本来自母亲。Rutter 在节目中把这件事与线粒体起源和疾病遗传联系起来；它不是一个与代谢无关的历史故事，而是今天研究线粒体疾病时必须保留的遗传线索。
吃进去的营养如何变成细胞指令
进食后，糖、氨基酸和脂肪进入血液，身体释放胰岛素、GLP-1 等激素信号。节目最重要的提醒是：同一个信号到达不同细胞后，不会产生同一个动作。
脂肪细胞对胰岛素尤其敏感。胰岛素会促使脂肪细胞启动葡萄糖摄取，再把葡萄糖经过一系列反应转成脂肪分子，安全地储存起来。禁食时，胰高血糖素发挥相反方向的作用，促使脂肪组织释放储存的脂肪。心脏尤其擅长使用脂肪酸，Rutter 在节目中估计，正常人的心肌能量来源约有 70% 到 80% 来自脂肪；心脏也能使用葡萄糖、乳酸、酮体和氨基酸。1
因此，胰岛素不是一辆单纯把葡萄糖“运进细胞”的班车。激素信号的强弱还告诉细胞，身体大概处于进食还是禁食状态，细胞再按自己的工作分配资源。脂肪细胞储存能量，肌肉细胞准备工作，其他细胞维持各自的任务。这个系统的重点不是让每个细胞拿到同样多的能量，而是让不同细胞把同一条全身信号翻译成不同的动作。
丙酮酸是“烧掉”还是“拿来建造”的分岔口
葡萄糖经过糖酵解（glycolysis）后形成丙酮酸（pyruvate）。丙酮酸是代谢路径上的关键分岔：它可以进入线粒体，被氧化并转化为 ATP；也可以留在细胞质里，成为合成新细胞所需材料的来源。心肌细胞偏向第一种路径，因为它需要不停收缩；肠道干细胞和正在制造大量抗体的 B 细胞，则需要把一部分资源投入蛋白质、核酸和膜的合成。
Huberman 用木材打了一个直观的比方：木材可以用来盖房子，也可以烧掉取暖；细胞有时必须烧掉一部分木材，才能维持盖房子的工程。这个比喻解释了“能量”和“生物量”为什么不能简单地排成好坏关系。细胞真正需要解决的问题，是在当下工作和未来扩增之间找到合适的分配。
细胞会持续感知自己的资源。当 ATP 降低时，细胞会关闭部分耗能过程，从外部摄取更多葡萄糖，优先恢复能量供应。类似的反馈也会出现在合成蛋白质所需的氨基酸、合成 DNA 和 RNA 所需的核苷酸上。细胞并不是把营养全部转成 ATP，再从 ATP 重新造出一切；细胞会根据任务保留不同的中间产物。
MPC：代谢地图上的一道闸门
MPC 是
mitochondrial pyruvate carrier，中文常译为“线粒体丙酮酸载体”。MPC1 和 MPC2 位于线粒体膜上，负责把丙酮酸送进线粒体。科学家几十年来都知道这条运输功能必须存在，却长期不知道具体是哪一种蛋白承担了它。Rutter 介绍，实验室从一批“已知在线粒体里、但功能未知”的蛋白中选出 MPC1 和 MPC2，再用酵母、果蝇和人类细胞等模型相互验证，提出它们就是线粒体丙酮酸载体；其他实验室随后也得出了相同结论。2MPC 的意义不只在于“多了一条通道”。丙酮酸能否进入线粒体，会影响它是被氧化、用于制造 ATP，还是留在细胞质中参与其他合成反应。MPC 因此成为“能量还是生物量”的一个入口。
Rutter 讲到一组很有解释力的实验。全身去除 MPC 的小鼠无法活到出生，大约在胚胎发育的第 12 至 13 天死亡。研究者后来使用条件性基因敲除，只在特定器官里去掉 MPC。心脏特异性去除 MPC 后，小鼠还能存活数周，但最终死于心力衰竭，心脏明显扩大。
关键点在于：这些心脏并非完全没有 ATP。心脏仍可以燃烧脂肪来生产 ATP，真正失常的是资源分配。葡萄糖不能正常进入线粒体氧化后，更多资源被转向制造生物量，心肌细胞变大，心脏结构逐渐失去有效泵血能力。Rutter 把这看成一个前沿问题：如果药物可以把这种病态的代谢分配重新接回健康路径，代谢治疗或许就不必只盯着“提高能量”这一件事。
细胞身份：做自己的工作，还是制造更多自己
MPC 实验让节目从代谢机制进入细胞身份。一个心肌细胞即使仍然保留心肌细胞的外观和部分标志，也可能把过多资源投入“变大”，而不是投入收缩和泵血。癌症、心脏异常扩大，以及某些免疫细胞过度活化导致的炎症，都可以被放到同一个更宽的框架里理解：细胞把资源过多投入制造更多东西，结果却损害了原本应该完成的功能。
Huberman 提到大型犬与小型犬寿命、IGF-1 生长通路等类比。Rutter 接受其中的核心问题，但强调这仍是一个需要精确测量的研究方向：细胞究竟怎样“知道”自己是谁？什么时候应该维持身份，什么时候应该扩增？一个成年人的组织也不是完全不变的原件，而是由早期基因组成和多年累积的突变共同构成的细胞拼图。这里的讨论提供了研究视角，不足以推出个人寿命或补剂选择的结论。
癌症：肿瘤怎样把代谢改成增殖机器
节目把癌细胞与病毒放在一起比较。病毒受到传播到下一个宿主的进化压力；癌细胞通常不会在人与人之间传播，演化主要发生在一个人的身体内部。一个细胞获得突变后，可能更快分裂、逃避免疫系统或绕过 DNA 损伤限制，随后在细胞群体内部继续被筛选。Rutter 认为，这种过程与进化有关，却与病毒寻找下一个宿主的传播逻辑不同。
癌细胞大量摄取葡萄糖，是节目解释代谢与疾病关系的另一个入口。临床上常用 FDG-PET 追踪带标记的葡萄糖，肿瘤组织往往因为摄取更多葡萄糖而显影。这个现象说明代谢可以帮助研究者观察疾病，但它本身不能告诉我们每一个肿瘤细胞究竟采用了哪一套资源分配方案。
节目没有把“癌症代谢”简化成一种单一的治疗靶点。不同肿瘤的突变背景、组织环境和营养供应都可能不同；一个通路被阻断后，细胞可能改用另一种燃料或另一条合成路径。Rutter 提到，未来的治疗方向可能是纠正错误的资源分配，但这仍处在研究和早期探索阶段。读者不能把这段访谈理解成癌症诊疗建议。
气味、成像与过量能量：哪些仍在前沿
Huberman 还问到，疾病是否可能通过呼出气体或身体气味被识别。节目把这件事放在研究前沿：气味来自化学物质，身体代谢改变后，呼出的化合物及其比例可能变化；但目前还不能把气味当作独立的临床筛查方法。它更像血液化学检测的远端线索，需要进一步确认化学特异性、稳定性和疾病之间的关系。
节目结尾回到“过量能量”。线粒体把食物中的能量转成 ATP 之前，能量会先以推动线粒体反应的形式存在。一个被广泛讨论的假说是，当线粒体处于能量过剩状态时，更容易产生 reactive oxygen species（活性氧，ROS）。ROS 可能损伤蛋白质和核酸，造成基因组损伤、突变和其他病理变化。Rutter 把这描述为重要但并非所有人都已接受的解释，并强调衰老机制仍只有部分答案。1
这也是本期最应该保留的证据边界：节目提供的是细胞机制、动物模型和研究方向。它帮助读者理解为什么“代谢健康”不能被压缩成一个体重数字，却没有给出一套适合所有人的饮食、运动或补剂处方。Huberman Lab 官方页面也注明，本期完整逐字稿仍处于人工审核中，自动字幕可能含有错误。23
人物背景
Andrew Huberman 是斯坦福医学院神经生物学与眼科学教授，也是 Huberman Lab 的主持人。本期嘉宾 Jared Rutter 是犹他大学生物化学杰出教授、Huntsman Cancer Institute 基因组学、表观遗传学与代谢项目联合负责人、代谢健康中心联合主任，并担任 Howard Hughes Medical Institute 研究员。Rutter 实验室研究细胞怎样感知代谢需求并作出响应；他的官方学术主页列出了围绕线粒体丙酮酸代谢、乳酸、心脏代谢、癌症和代谢调控的研究。4
Rutter 适合谈这期主题，原因在于他的研究一直围绕“细胞如何分配营养”展开，而不是因为他能把一套生活方式建议包装成线粒体秘诀。节目真正提供给读者的价值，是一个判断健康科学信息的框架：先问讨论发生在哪种细胞、资源走向哪条路径、证据来自哪种模型，再判断这项发现距离普通人的临床决策还有多远。
完整双语自动转录
以下转录取自本期官方 YouTube 完整自动字幕。Huberman Lab 的官方页面说明，人工审核版本尚未发布，因此原文保留口语、重复、广告片段和可能的识别错误；本篇只根据官方学术资料校正了 Andrew Huberman、Jared Rutter、MPC 等明确可核对的专名，没有把听感推测改写成事实。12
官方自动字幕没有逐段讲话人声纹，视频下载路径也未能取得可用的说话人分离结果。因此每个转录单元使用“讲话人（自动字幕未标注）”标签；这比把一段话错误归给主持人或嘉宾更诚实。时间轴按完整字幕的文字位置与官方 2:03:47 时长线性估算，每 10 分钟标记一次，不代表原始字幕提供了精确时间码。每段先列英文原文，紧跟中文机器翻译；译文用于理解，英文原文才是逐字稿的主文本。
00:00:00
讲话人（自动字幕未标注）：
There's a widely accepted hypothesis that mitochondria with excess energy leads to problems. Many people that that are listening have probably heard of reactive oxygen species. This is forms of oxygen that become reactive and end up spinning out and damaging proteins and nucleic acids. And I think it is widely accepted that one of the contributors to that is mitochondria that have too much energy. Basically, the
有一个广泛接受的假设，即线粒体能量过剩会导致问题。许多正在听的人可能听说过活性氧。这是氧气的形式，会变得活跃并最终旋转并破坏蛋白质和核酸。我认为人们普遍认为造成这一现象的原因之一是线粒体能量过多。基本上，
讲话人（自动字幕未标注）：
form that energy takes when it's extracted from the food we eat and before it's converted to ATP is powering the mitochondria. And when that mitochondria is overpowered, that leads to a state that is very susceptible to generation of these reactive species that end up damaging our genome, creating mutations and damaging proteins and creating many of the problems that we see. Welcome to the Hubberman Lab podcast,
从我们吃的食物中提取能量并在转化为 ATP 之前所采取的能量形式为线粒体提供动力。当线粒体被压倒时，就会导致一种非常容易产生这些活性物质的状态，这些活性物质最终会破坏我们的基因组，产生突变和破坏蛋白质，并造成我们看到的许多问题。欢迎来到哈伯曼实验室播客，
讲话人（自动字幕未标注）：
where we discuss science and science-based [music] tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and opthalmology at Stanford School of Medicine. My guest today is Dr. Jared Ruer. Dr. Jared Ruer is a professor of biochemistry at University of Utah and an investigator with the Howard Hughes Medical Institute. He is one of the world's top experts in the biology of mitochondria and
在那里我们讨论日常生活中的科学和基于科学的[音乐]工具。我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。今天我的嘉宾是贾里德·鲁尔博士。 Jared Ruer 博士是犹他大学生物化学教授，也是霍华德休斯医学研究所的研究员。他是线粒体生物学领域的世界顶级专家之一
讲话人（自动字幕未标注）：
metabolism. Mitochondria are known as the powerhouse of the cell. But as you'll learn today, they do far more than just power our cells. They also determine how much energy goes into making new cells, to making sure that cells stay healthy, and to fighting off disease. Today's conversation explains how mitochondria do that, and clarifies what your metabolism really is. And in doing so, you will learn that you don't
代谢。线粒体被称为细胞的动力室。但正如您今天将了解到的，它们的作用远不止为我们的细胞提供动力。它们还确定有多少能量用于制造新细胞、确保细胞保持健康以及抵抗疾病。今天的对话解释了线粒体如何做到这一点，并阐明了新陈代谢的真正含义。在这样做的过程中，你会发现你不
讲话人（自动字幕未标注）：
have one metabolism. Your metabolism as it's called is actually a reflection of the constellation of all the metabolisms of all the cells in your body. So today's conversation will teach you the real biology of mitochondria and it will provide a framework for you to make better decisions on the behalf of your health. So what follows is a conversation about mitochondria and metabolism unlike any that you've heard
有一种新陈代谢。所谓的新陈代谢实际上反映了您体内所有细胞的所有新陈代谢。因此，今天的对话将教您线粒体的真正生物学知识，并将为您提供一个框架，以便您可以为自己的健康做出更好的决定。接下来是关于线粒体和新陈代谢的对话，与您听过的任何对话都不一样
讲话人（自动字幕未标注）：
from one of the world's premier experts in this topic. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with
来自该主题的世界顶级专家之一。在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。然而，我的愿望和努力的一部分是向公众提供有关科学和科学相关工具的零成本消费者信息。为了与这个主题保持一致，今天的节目确实有赞助商。现在我与
讲话人（自动字幕未标注）：
Dr. Jared Ruer. Dr. Jared Ruer, welcome. >> Thank you. Thanks for having me on. >> I have many questions about metabolism, mitochondria, and I know many people do as well. Most people hear the word metabolism and they think calories in, calories out. They hear the word mitochondria and they probably think the powerhouse of the cell and that's all great. People are becoming more educated about cells and their bits
贾里德·鲁尔博士。贾里德·鲁尔博士，欢迎光临。 >> 谢谢。谢谢你邀请我参加。 >> 我对新陈代谢、线粒体有很多疑问，我知道很多人也有同样的疑问。大多数人听到新陈代谢这个词，他们会想到卡路里的摄入和卡路里的消耗。他们听到线粒体这个词，可能会认为它是细胞的动力源，这一切都很棒。人们对细胞及其片段的了解越来越多
讲话人（自动字幕未标注）：
and pieces and what they do. You have a very different perspective that is very important I believe for people to understand. Maybe we could start off by talking about how the metabolism of any one cell in our body relates to what we call our metabolism, the collective metabolism of all those cells. And as you go, if you could take any liberties you want to tell us what we probably don't know about the quote unquote
以及它们的作用。你有一个非常不同的观点，我相信这对于人们理解非常重要。也许我们可以首先讨论我们体内任何一个细胞的新陈代谢如何与我们所说的新陈代谢（所有这些细胞的集体新陈代谢）相关。顺便说一句，如果您可以冒昧地说一下，您想告诉我们关于引用 unquote 可能不知道的内容
讲话人（自动字幕未标注）：
powerhouses of the cell. >> Yeah. You know, when we think about metabolism, as you say, I think all of us think about metabolism in terms of our body's metabolism, our metabolic rate, as you say, calories in, calories out. What that is really our body's metabolism is basically the the sum total of what we ingest, you know, what we eat, what we drink, what we breathe, that enters our body and gets processed. And the
细胞的发电厂。 >> 是的。你知道，当我们考虑新陈代谢时，正如你所说，我认为我们所有人都从我们身体的新陈代谢、新陈代谢率、卡路里摄入、卡路里排出的角度来考虑新陈代谢。我们身体真正的新陈代谢基本上是我们摄入的东西的总和，你知道，我们吃的东西、我们喝的东西、我们呼吸的东西，进入我们的身体并被加工。还有
讲话人（自动字幕未标注）：
results of that processing are individual molecules, amino acids and sugars and so forth that then distribute throughout the body go into individual cells and enter this process that we call metabolism and we call cellular metabolism. And I think it's reasonable to think of cellular metabolism as almost like a map. There's an entry point. A molecule of glucose or sugar comes into a cell and that sugar can be
该处理的结果是单个分子、氨基酸和糖等，然后分布在整个身体中，进入单个细胞并进入这个我们称为新陈代谢和细胞新陈代谢的过程。我认为将细胞新陈代谢视为一张地图是合理的。有一个入口点。葡萄糖或糖分子进入细胞，并且该糖可以
讲话人（自动字幕未标注）：
chemically modified in a variety of ways to fulfill the needs of that cell. And then that cell does whatever it needs to do with the molecules it takes in to fulfill its particular functions. And then that leads to the um release of waste products that we eliminate from our body. And that is sort of the organismal metabolism, the metabolism of our body. And as you allude to, I think something that maybe many people
以各种方式进行化学修饰以满足该细胞的需求。然后，该细胞会利用它所吸收的分子做任何需要做的事情，以实现其特定的功能。然后这会导致我们从体内排出废物的释放。这就是有机体的新陈代谢，我们身体的新陈代谢。正如你提到的，我认为也许很多人
讲话人（自动字幕未标注）：
don't understand is that cellular piece of it. The metabolism of our body is really the sum total of the metabolism of each one of our 30 trillion cells or so. That's really where my passions lie are those individual cells and how they choose to take up certain nutrients, how they choose how to process them, turn them into other things, how they use them to fulfill their particular functions, and how that's
不明白的是它的细胞部分。我们身体的新陈代谢实际上是我们大约 30 万亿个细胞中每一个细胞新陈代谢的总和。这确实是我的热情所在，那些个体细胞以及它们如何选择吸收某些营养物质，它们如何选择如何处理它们，将它们转化为其他东西，它们如何使用它们来实现它们的特定功能，以及它们是如何实现的。
讲话人（自动字幕未标注）：
regulated. the masterful coordination of each of those cells working together to allow us to be sitting here talking to one another and go out and run or whatever we do. It's a beautiful orchestration, but that happens at the level of of individual cells. And I think that's one of the fascinating things that is maybe a little bit less understood. if we were to just take the single cell view for a moment and I know
受监管。每个细胞的巧妙协调在一起工作，使我们能够坐在这里互相交谈，然后出去跑步或做任何我们做的事情。这是一个美妙的编排，但这发生在单个细胞的层面上。我认为这是一件令人着迷的事情，但人们可能不太了解。如果我们只看一下单细胞视图，我知道
讲话人（自动字幕未标注）：
that aging isn't a like your specific area of interest but one thing that's always intrigued me because my postto adviser once came down the hall and said why do I have so much less energy than I used to and he had a ton of energy so that I like I wonder what he used to be like but it's a great question he used to do this every once in a while like just ask these very basic questions that no one else on our halls at
衰老并不像你感兴趣的特定领域，但有一件事总是让我感兴趣，因为我的邮递顾问曾经走过大厅，说为什么我的精力比以前少了这么多，而他却精力充沛，所以我喜欢我想知道他过去是什么样子，但这是一个很好的问题，他曾经偶尔这样做，就像只问这些非常基本的问题，我们大厅里没有其他人问
讲话人（自动字幕未标注）：
Stanford could really answer why does a kid have so much energy and when we're older We don't what people say well people are moving less the tissues are wearing out but at the level of energy production are we aware as biologists at this point in history as to why a young cell could be muscle cell it could be neuron whatever versus an older version of that cell why it it either produces less energy I don't know if
斯坦福大学确实可以回答为什么孩子有这么多的能量，而当我们长大时，我们并不像人们所说的那样，人们移动得更少，组织磨损，但在能量产生的水平上，作为生物学家，我们在历史的这一点上是否意识到为什么年轻的细胞可以是肌肉细胞，它可以是神经元，而与旧版本的细胞相比，为什么它产生的能量更少我不知道是否
讲话人（自动字幕未标注）：
it does I'm guessing it might but why the whole body just seems to have less get up and go do we have an answer for Yeah, I think we have a partial answer for that. I think that's a that's definitely a frontier of science is trying to understand exactly what goes wrong during aging. There's many aspects to it. As you alluded to, one of my passions also is the mitochondria. And I think it's almost universally the
确实如此，我猜可能是这样，但为什么整个身体似乎很少起身走动，我们有答案吗？是的，我想我们对此有部分答案。我认为这绝对是科学的前沿领域，它试图准确地理解衰老过程中到底出了什么问题。这有很多方面。正如你提到的，我的热情之一也是线粒体。我认为这几乎是普遍的
讲话人（自动字幕未标注）：
case that mitochondria become less energized, less effective, let's say, as we age. And the reasons for for that are to some extent clear but I think largely unclear but that is definitely a feature of the aging process. You know there there is this sort of aspect of accumulation of damage. You know living in the world we live in as I alluded to before this orchestration of metabolism that happens throughout the
比如说，随着年龄的增长，线粒体的活力和效率都会降低。其原因在某种程度上是明确的，但我认为很大程度上还不清楚，但这绝对是衰老过程的一个特征。你知道有这种损害累积的方面。你知道生活在我们生活的世界中，正如我在整个新陈代谢发生的协调之前提到的那样
讲话人（自动字幕未标注）：
body. That's hard. It's expensive. And it's expensive not only in terms of what we need to eat to fuel it, but it's expensive in terms of the damage that can come as a side effect of that. And the accumulation of that damage over time is certainly correlated strongly with aging. And I think there's some really nice evidence in models where we can do genetics, you know, in in animal models that suggests that that
身体。那很难。它很贵。它的昂贵不仅在于我们需要吃什么来补充能量，而且就其副作用可能带来的损害而言也是昂贵的。随着时间的推移，这种损害的积累肯定与衰老密切相关。我认为在我们可以进行遗传学研究的模型中有一些非常好的证据，你知道，在动物模型中表明
讲话人（自动字幕未标注）：
accumulation of damage is a big part of the aging process. And it's a huge area of interest in the field is trying to understand how you can decrease the onset of damage, how you can reverse damage that comes. One thing that I like about how you ask that question is thinking about that in the context of the cell, which again I don't think we t tend to think of aging as a cellular phenomenon, but I think
损伤的积累是衰老过程的重要组成部分。该领域的一个巨大兴趣领域是试图了解如何减少损害的发生，如何扭转所发生的损害。我喜欢你问这个问题的方式是在细胞的背景下思考这个问题，我再次认为我们不倾向于将衰老视为一种细胞现象，但我认为
讲话人（自动字幕未标注）：
fundamentally it almost has to be. We are made up of cells and the processes that lead to aging are the accumulation of processes that happen at the level of individual cells. And I think in a way we're at the precipice of understanding a lot of this because of the tools that we are um starting to have access to that will help us better understand cause and effect and the specific molecular features of of the aging
从根本上来说，这几乎是必须的。我们是由细胞组成的，导致衰老的过程是在单个细胞水平上发生的过程的累积。我认为在某种程度上我们正处于理解这一点的边缘，因为我们开始使用的工具将帮助我们更好地理解因果关系以及衰老的具体分子特征
讲话人（自动字幕未标注）：
process. Let's talk about mitochondria. Perhaps surprisingly, I'm going to ask you why you study them with the caveat that they are incredibly interesting. They are involved in energy production and metabolism. But what what specifically drew you to mitochondria versus all the other pieces of cells or parts of the body or organs that you could have worked on? Why the mitochondria? What what's so sticky about those
过程。我们来谈谈线粒体。也许令人惊讶的是，我会问你为什么要研究它们，并警告它们非常有趣。它们参与能量产生和新陈代谢。但是，与您可以研究的所有其他细胞或身体部位或器官相比，是什么特别吸引您选择线粒体呢？为什么是线粒体？那些东西有什么粘性
讲话人（自动字幕未标注）：
as a place to I mean you devote a significant fraction of your life to them? Yeah, it's an area of cell biology, an area of sort of the details of how life works. One of these things that is, in my view, just a brilliant example of taking in chemistry of incredible complexity and making it work effectively inside of a a living cell. Mitochondria are believed to have been the result of an endo symbiotic event where a
作为一个地方，我的意思是你将生命的很大一部分奉献给他们？是的，这是细胞生物学的一个领域，是一个研究生命如何运作的细节的领域。在我看来，其中之一就是吸收极其复杂的化学物质并使其在活细胞内有效发挥作用的一个绝妙例子。线粒体被认为是内共生事件的结果，其中
讲话人（自动字幕未标注）：
bacterium a free-living bacterium was engulfed by another cell and in a way kind of domesticated. So wild to think about totally wild. I'm sure people are following, but in case there's somebody who's not, >> what Jared is saying is that our cells basically were invaded by a bacterium and then that bacterium became part of our stable genome going forward. It went into the what we call the germ line and therefore was
细菌 一种自由生活的细菌被另一个细胞吞噬并以某种方式被驯化。想想真是太疯狂了。我确信人们正在关注，但万一有人没有关注，>> Jared 所说的是，我们的细胞基本上被细菌入侵，然后该细菌成为我们稳定基因组的一部分。它进入了我们所说的种系，因此
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讲话人（自动字幕未标注）：
propagated from parents to kids. And so now mitochondria live in us, but they didn't start off living in us. >> That's right. And I and we hear that about the gut microbiome like we have these trillions of bacteria that live in us and we colonize and we can recolonize take antibiotics and then you need to replenish eat your yogurt and so on. But but the fact that the mitochondria made it stably into our genome and
从父母传给孩子。所以现在线粒体生活在我们体内，但它们并不是一开始就生活在我们体内的。 >> 没错。我和我们听说关于肠道微生物组，就像我们体内生活着数万亿个细菌，我们可以定殖，我们可以重新定殖，服用抗生素，然后你需要补充营养，吃酸奶等等。但事实上线粒体已经稳定地进入我们的基因组并且
讲话人（自动字幕未标注）：
are transmitted from one generation to the next. We think of them as us but you're saying there is solid evidence that they came from outside of humans. >> I think that's the only model that I think any of us as scientists have any good reason to believe. And you know that's fascinating history, right? That there was a bacteria and another cell that got together and and together that combination could do things that
是从一代传给下一代的。我们认为他们就是我们，但你说有确凿的证据表明他们来自人类之外。 >> 我认为这是我们科学家有充分理由相信的唯一模型。你知道那是一段令人着迷的历史，对吧？有一种细菌和另一种细胞结合在一起，这种组合可以做一些事情
讲话人（自动字幕未标注）：
that any one of either of them on their own could not do and that they work together in in some way to enable the evolution of complex life. you know ukarotes which are the the type of cell that resulted from that combined situation that we were just talking about. These are all the organisms that we see around us. Plants, animals, fungi even are all the result of these two cells getting together and making peace so
它们中的任何一个都无法单独做到这一点，并且它们以某种方式协同工作以实现复杂生命的进化。你知道 ukarotes，这是我们刚才讨论的综合情况产生的细胞类型。这些是我们在周围看到的所有生物体。植物、动物、甚至真菌都是这两种细胞走到一起和平相处的结果，所以
讲话人（自动字幕未标注）：
to speak and uh teaming up to make this synergistic cell. >> Is it synergistic? for forgive me for interrupting, but when I think about viruses, I think viruses have their own sort of intelligence. They kind of they hijack the genomes of cells and they either kill those cells or if they're really smart, they keep them those cells alive and use those cells to continue to live and then propagate through like the
说话和呃合作组成这个协同细胞。 >> 有协同作用吗？请原谅我打断，但是当我想到病毒时，我认为病毒有自己的智能。他们劫持了细胞的基因组，他们要么杀死这些细胞，要么如果他们真的很聪明，他们会让这些细胞存活并利用这些细胞继续生存，然后像
讲话人（自动字幕未标注）：
behavior of an animal like the rabies virus like, oh, let's get this animal aggressive so that it bites and then I mean viruses don't think, but they have an intelligence. Do we know that the mitochondria were benefiting the cells and the cells were benefiting the mitochondria or could have this been a takeover by the by the mitochondria? >> I mean, this is a a bit of a philosophical question. Of course, we don't
像狂犬病病毒这样的动物的行为就像，哦，让我们让这种动物具有攻击性，这样它就会咬人，然后我的意思是病毒不会思考，但它们有智力。我们是否知道线粒体使细胞受益，细胞也使线粒体受益，或者这可能是线粒体的接管？ >> 我的意思是，这是一个有点哲学问题。当然，我们不
讲话人（自动字幕未标注）：
have a record of of what exactly happened when and who benefited in real time, but one thing we do know is all of complex life resulted from cells that underwent that event. One time or multiple times, but all of complex life evolved from that. And I think that tells us that more than likely complex life could not result from a bacteria on its own or the archa the the the cell that became the host for that bacteria.
记录了到底发生了什么、何时以及谁实时受益，但我们确实知道的一件事是，所有复杂的生命都是由经历该事件的细胞产生的。一次或多次，但所有复杂的生命都由此演化而来。我认为这告诉我们，复杂的生命很可能不是由细菌本身或古细菌（成为该细菌宿主的细胞）产生的。
讲话人（自动字幕未标注）：
So I think you can make a compelling argument that this was beneficial. And one reason it was beneficial because it enabled a form of metabolism that wasn't possible before and enabled now a more complex cell to be able to do things metabolically to be more metabolically efficient and and and diversified that it could enable you know again complex life to evolve and totally fascinating history but I think as you
所以我认为你可以提出一个令人信服的论据，证明这是有益的。它有益的一个原因是，它实现了一种以前不可能的新陈代谢形式，现在使更复杂的细胞能够以代谢方式做事，代谢效率更高，而且多样化，它可以让你再次了解复杂的生命进化和完全迷人的历史，但我认为，正如你一样
讲话人（自动字幕未标注）：
alluded to also has very interesting implications for life today. I would like to take a quick break and acknowledge one of our sponsors, JWVE. JWVE makes medical grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast, is the incredible impact that light can have on our biology and our health. Now, in addition to sunlight, which I've talked about a lot on this
提到的对今天的生活也有非常有趣的影响。我想稍微休息一下并感谢我们的赞助商之一 JWVE。 JWVE 生产医疗级红光治疗设备。现在，如果我在这个播客中一直强调一件事，那就是光对我们的生物学和健康产生的令人难以置信的影响。现在，除了阳光之外，我在这方面已经谈论了很多
讲话人（自动字幕未标注）：
podcast, red light, near infrared, and infrared light have been specifically shown to have positive effects on improving numerous aspects of cellular and organ health. These include faster muscle recovery, improved skin health, wound healing, improvements in acne, reduced pain and inflammation, improved mitochondrial function, and even improvements in vision. Nowadays, there are a lot of red light devices out there.
播客、红光、近红外光和红外光已被具体证明对改善细胞和器官健康的许多方面具有积极作用。这些包括更快的肌肉恢复、改善皮肤健康、伤口愈合、改善痤疮、减少疼痛和炎症、改善线粒体功能，甚至改善视力。现在市面上有很多闯红灯的装置。
讲话人（自动字幕未标注）：
But what sets Juv lights apart, and why they're my preferred red light therapy device, is that they use clinically proven wavelengths, meaning they use the specific wavelengths of red light, near infrared, and infrared light in combination to trigger the optimal cellular adaptations. Personally, I use the Juv whole body panel about three to four times a week, usually for about 10 to 20 minutes per session. And I use
但 Juv 灯的与众不同之处以及它们成为我首选红光治疗设备的原因在于它们使用经过临床验证的波长，这意味着它们结合使用特定波长的红光、近红外光和红外光来触发最佳的细胞适应。就我个人而言，我每周使用 Juv 全身面板大约三到四次，通常每次大约 10 到 20 分钟。我用
讲话人（自动字幕未标注）：
the Juv handheld light both at home and when I travel. If you would like to try JWV, they're offering up to $400 off select products for listeners of this podcast. To learn more, visit juv, spelled jv.com/huberman. Again, that's jovv.com/huberman. Today's episode is also brought to us by BetterHelp. BetterHelp offers professional therapy with a licensed therapist carried out entirely online. I've been doing therapy
Juv 手持灯无论是在家里还是在旅行时。如果您想尝试 JWV，他们将为该播客的听众提供精选产品高达 400 美元的折扣。要了解更多信息，请访问 juv（拼写为 jv.com/huberman）。再说一遍，这是 jovv.com/huberman。今天的节目也是由 BetterHelp 为我们带来的。 BetterHelp 提供由持照治疗师完全在线进行的专业治疗。我一直在做治疗
讲话人（自动字幕未标注）：
for a long time, and while it's not always easy, every time I do a therapy session, I come away feeling better and knowing that the time was well spent. With BetterHelp, they make it extremely easy to find an expert therapist who can help provide the benefits that come through effective therapy. And the data say it works. BetterHelp has an average rating of 4.9 out of five for its live sessions based on over 1.7
很长一段时间以来，虽然这并不总是那么容易，但每次我进行治疗时，我都会感觉更好，并且知道时间花得很值。通过 BetterHelp，他们可以非常轻松地找到可以帮助提供有效治疗带来的好处的专家治疗师。数据表明它有效。 BetterHelp 的现场会议平均评分为 4.9 分（满分 5 分），评分超过 1.7 分
讲话人（自动字幕未标注）：
million client reviews. Also, because BetterHelp is done entirely online, it's extremely timeefficient. If you would like to try BetterHelp, go to betterhelp.com/huberman to get 10% off your first month. Again, that's betterhelp.com/huberman. Could we explore a little bit of how mitochondria getting into these cells were able to make it stably into their genome and propagate? This isn't going to be a conversation
百万客户评论。此外，由于 BetterHelp 完全在线完成，因此非常省时。如果您想尝试 BetterHelp，请访问 betterhelp.com/huberman，第一个月可享受 10% 的折扣。再说一次，这是 betterhelp.com/huberman。我们能否探索一下进入这些细胞的线粒体如何能够稳定地进入其基因组并繁殖？这不会是一场对话
讲话人（自动字幕未标注）：
about genetics per se, but I maybe as a just two points of background for people like if any of our cells have something put into them, but let's say a physical object like a splinter, little tiny piece of splinter stays in the cell and then you procreate with somebody, you don't expect that child will have that little bits of splinter in their cells. But if the germ line, right, so the the eggs or the sperm have
关于遗传学本身，但我可能只是为人们提供两点背景知识，比如如果我们的任何一个细胞中放入了一些东西，但比方说一个像碎片这样的物理物体，一小片碎片留在细胞中，然后你和某人生育，你不会指望那个孩子的细胞中会有那么一点碎片。但如果生殖系正确，那么卵子或精子就有
讲话人（自动字幕未标注）：
something incorporated into them, then potentially it could propagate is why they call germline as opposed to sematic cells. I think most people aren't aware of that. It makes perfect sense once you hear it, but you're talking about many, many, many years ago >> a cell having this bacterium go into it and then it was somehow able to stably represent itself in the genome. So that that propagated forward and
某些东西融入到它们中，然后它可能会传播，这就是为什么他们称之为生殖细胞而不是精细胞。我想大多数人都没有意识到这一点。一旦你听到它，它就完全有道理了，但你说的是很多很多很多年前>>一个细胞中有这种细菌进入其中，然后它以某种方式能够在基因组中稳定地代表自己。这样就可以向前传播并
讲话人（自动字幕未标注）：
eventually >> it has to be in the germ line of whatever you know primordial homo sapiens were there otherwise >> your kids I you wouldn't have mitochondria in us how do we think that might have happened >> the main genome of the cell the cellular genome DNA contained typically in the nucleus of the cell mitochondria exists in the cytool outside the nucleus one of the interesting things about mitochondria which I
最终>>它必须存在于你所知道的任何原始智人的种系中，否则的话>>你的孩子，我你不会在我们体内有线粒体我们认为这可能是如何发生的>>细胞的主要基因组细胞基因组 DNA 通常包含在细胞核中线粒体存在于细胞核外的细胞质中关于线粒体的有趣的事情之一我
讲话人（自动字幕未标注）：
think is totally fascinating and has really interesting disease implications and worthy of talking about. We may or may not come back to it is that mitochondria have their own separate genome that is sort of a relic of the bacterium that they are the descendants of. It's in a circle like the bacterial genomes. Whereas the nuclear genome of a ukareotic cell is linear chromosomes. And that genome performs very
认为非常令人着迷，并且具有非常有趣的疾病影响并且值得谈论。我们可能会也可能不会回到这一点：线粒体有自己独立的基因组，这是它们后代细菌的遗迹。它像细菌基因组一样呈一个圆圈。而核细胞的核基因组是线性染色体。该基因组表现非常好
讲话人（自动字幕未标注）：
essential functions and codes very important proteins that enable our mitochondria to function as the powerhouse of the cell which we uh know them to be to enable the extraction of usable energy from the food that we eat. So, as you alluded to, those cytoplasmic mitochondria somehow make it from generation to generation. And one of the interesting features of them being cytoplasmic is they're completely inherited
基本功能和编码非常重要的蛋白质，使我们的线粒体能够充当细胞的动力室，我们知道它们能够从我们吃的食物中提取可用的能量。因此，正如您所提到的，这些细胞质线粒体以某种方式代代相传。它们是细胞质的有趣特征之一是它们是完全遗传的
讲话人（自动字幕未标注）：
from the mom, from the egg, cuz as you know, when the sperm invades the egg, the the genome from the sperm gets into the the egg, fertilizes it. The cytoplasm of the sperm does not. So the mitochondrial genome of you came completely from your mother. Mine came completely from my mother. And again that has interesting implications for the inheritance of uh diseases that are mitochondrial on origin. But that's sort of
来自母亲，来自卵子，因为如你所知，当精子侵入卵子时，精子的基因组进入卵子，使其受精。精子的细胞质则不然。所以你的线粒体基因组完全来自你的母亲。我的完全来自我母亲。这对于起源于线粒体的呃疾病的遗传也有有趣的影响。但这有点像
讲话人（自动字幕未标注）：
how we think it works. It basically propagates from the egg upon fertilization. Then it gets distributed to all the cells including the the germ line that that fertilized embryo will have and then gets passed on to the next generation in [snorts] the same way >> ratcheting toward the actual functioning of mitochondria. Maybe um you give a beautiful picture of the mitochondria not uh in the nucleus of the cell but in
我们认为它是如何运作的。它基本上是在受精后从卵子繁殖的。然后它被分配到所有细胞，包括受精胚胎将具有的生殖系，然后以相同的方式传递给下一代>>朝着线粒体的实际功能发展。也许嗯，你给出了一幅美丽的线粒体图片，不是在细胞核中，而是在细胞核中。
讲话人（自动字幕未标注）：
the cytoplasm. So still inside the cell and most people probably remember from their high school biology a picture of a cell always looks round. Mhm. >> I'm guessing you're going to tell us that the mitochondria can be distributed lots of places in a cell cuz a lot of cells aren't round. A lot of them look hairy or they have long extensions like neurons. Is it fair to say that you can find mitochondria everywhere in
细胞质。因此，仍然在细胞内部，大多数人可能还记得高中生物学中的一张细胞的图片总是看起来是圆形的。嗯。 >> 我猜你会告诉我们线粒体可以分布在细胞中的很多地方，因为很多细胞不是圆形的。它们中的许多看起来毛茸茸的，或者有像神经元一样的长延伸物。可以说线粒体随处可见吗？
讲话人（自动字幕未标注）：
a cell? So no matter what shape it is, it's got mitochondria everywhere. And if so, what is the importance of having mitochondria distributed spatially through the cell? So maybe we go so people know where we're going. We we'll talk about the spatial distribution because it turns out that's very important. We'll talk about the functioning and then I want to talk about time as a factor and that can be a little bit
一个细胞？所以无论它是什么形状，它到处都有线粒体。如果是这样，线粒体在细胞中空间分布的重要性是什么？所以也许我们去是为了让人们知道我们要去哪里。我们将讨论空间分布，因为事实证明这非常重要。我们将讨论功能，然后我想谈谈时间这个因素，这可能有点
讲话人（自动字幕未标注）：
abstract for people. So we'll come to that. >> Yeah. Spatially, you know, I I one of my scientist colleagues might call me on this but to my know I can't think of a place that exists in cells where there aren't mitochondria. And I think as you alluded to I it's a little bit dangerous for me to talk about neurons with a neuroscientist. I am not a neuroscientist but one of the brilliant bodies of work that's been done
对人们来说是抽象的。所以我们会谈到这一点。 >> 是的。在空间上，你知道，我的一位科学家同事可能会打电话给我，但据我所知，我想不出细胞中存在没有线粒体的地方。我认为正如你所提到的，与神经科学家谈论神经元对我来说有点危险。我不是神经科学家，但已完成的杰出工作之一
讲话人（自动字幕未标注）：
on mitochondria has been done in neurons. It's fascinating these these neurons that have one meter long projections and mitochondria transit from the cell body down those projections and as best we can tell those mitochondria play essential roles at the ends of those projections typically being able to generate again usable energy. They're extracting the energy from the food that we eat and powering the
线粒体的研究已在神经元中完成。令人着迷的是，这些神经元具有一米长的突出物，线粒体从细胞体向下传输到这些突出物，我们可以说，这些线粒体在这些突出物的末端发挥着重要作用，通常能够再次产生可用的能量。它们从我们吃的食物中提取能量并为我们提供动力
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讲话人（自动字幕未标注）：
neurotransmission the the functions of those nerve nerve terminals. And I think that's true of virtually every cell in our body. The extraction of energy and turning it into use a usable form typically in the form of ATP adenosine triphosphate. Obviously that is the energy currency that's used by almost every cell in our body and that is a key function of mitochondria. We'll probably come to functions of
神经传递是那些神经神经末梢的功能。我认为我们身体中几乎每个细胞都是如此。提取能量并将其转化为可用的形式，通常以 ATP 三磷酸腺苷的形式。显然，这是我们体内几乎每个细胞都使用的能量货币，也是线粒体的关键功能。我们可能会遇到以下函数
讲话人（自动字幕未标注）：
mitochondria that are outside of just extracting energy, but that is a critical function of mitochondria and that ATP is needed in virtually every place of every cell and by having local production that makes it more efficient. So I think spatial distribution is a key part of that. It's fascinating. There's been beautiful work that's shown that when a cell is crawling as cells sometimes do you know like an immune
线粒体不只是提取能量，但这是线粒体的一项关键功能，几乎每个细胞的每个地方都需要 ATP，通过本地生产可以提高效率。所以我认为空间分布是其中的关键部分。这很有趣。有一项出色的工作表明，当细胞像细胞一样爬行时，有时你会像免疫系统一样知道
讲话人（自动字幕未标注）：
cell that sees something it's chasing there will be a distribution of mitochondria towards that leading edge of the cell which is very energetically expensive to crawl for a cell requires a lot of ATP and mitochondria will congregate at that leading edge where that ATP is being consumed to make ATP right there so it can be used I think it's fascinating example of that local uh demand for energy. >> I'm asking some
当细胞看到它正在追逐的东西时，线粒体就会向细胞的前缘分布，这对于细胞的爬行来说是非常耗费能量的，因为细胞需要大量的 ATP，线粒体会聚集在前缘，在那里 ATP 被消耗，在那里产生 ATP，这样它就可以被使用，我认为这是当地对能量的需求的一个有趣的例子。 >> 我问一些
讲话人（自动字幕未标注）：
highle questions I realize, but is there any reason to believe that a a given mitochondria knows what cell it belongs to? >> Like the like are they different? Is is are the mitochondria in one cell type so very different than the mitochondria in another cell type? or the mitochondria between like let's say a neuron of the eye versus let's get out and since you're saying you don't want to talk neurons as a per se
我意识到这个问题很严重，但是有什么理由相信给定的线粒体知道它属于哪个细胞呢？ >> 就像他们有什么不同吗？一种细胞类型中的线粒体与另一种细胞类型中的线粒体有很大不同吗？或者线粒体就像眼睛的神经元和让我们出去一样，因为你说你不想谈论神经元本身
讲话人（自动字幕未标注）：
like is two adjacent skin cells they're both skin cells they have mitochondria in them but do they know which cell they belong to >> and do your mitochondria I'm guessing because they came from your mom's genome they know that they're different than my mitochondria but how much identity do they have >> yeah I would say this is a topic that is at the frontier of what we No, you're you're asking some questions that
就像是两个相邻的皮肤细胞，它们都是皮肤细胞，它们里面有线粒体，但它们知道它们属于哪个细胞吗>>并且你的线粒体我猜是因为它们来自你妈妈的基因组，它们知道它们与我的线粒体不同，但它们有多少身份>>是的，我会说这是一个处于我们前沿的话题不，你是你问的一些问题
讲话人（自动字幕未标注）：
are right at the edge of our current knowledge. Yeah, mitochondria are different. To a first approximation, you could say that virtually every cell in our body has slightly different mitochondria that are particularly suited to the demands of that cell. a heart muscle cell, a cardiammyioite, that cell kind of has one job and that's to contract every second of every minute of every hour of every day for our entire
就在我们当前知识的边缘。是的，线粒体是不同的。初步估计，我们体内的几乎每个细胞都有稍微不同的线粒体，它们特别适合该细胞的需求。心肌细胞，cardiammyioite，这种细胞有一项工作，那就是在我们整个生命周期中，每一天、每一小时、每一分钟、每一秒都收缩
讲话人（自动字幕未标注）：
life. And when it coordinates that contraction with the other cells in the heart, that enables our heart to beat. That's what its job is. >> Is there any turnover of those cells? We know neurons don't tend to turn over. >> Very little. Very little. >> Well, that's reassuring. >> Very very little. I'm glad you >> you can imagine that it would be hard to replace that in real time, right? That's a I'm a hockey fan and
生活。当它与心脏中的其他细胞协调收缩时，我们的心脏就能跳动。这就是它的工作。 >> 这些细胞有更新吗？我们知道神经元不会翻转。 >> 很少。很少。 >> 嗯，这让人放心。 >> 非常非常少。我很高兴您>>您可以想象实时替换它会很困难，对吧？那是我是一名曲棍球迷并且
讲话人（自动字幕未标注）：
that's a change on the fly scenario of biblical proportions. So that those cardiammyioytes, >> their mitochondria is wired >> to consume whatever it has available and make ATP because that ATP is is going to be incredibly important to enable that contraction of that cell and the beating of the heart. mitochondria and other cells. For example, like cells that line that that are the stem cells that that enable our
这是圣经中的即时场景变化。因此，那些心肌细胞，>>它们的线粒体>>会消耗任何可用的物质并产生 ATP，因为 ATP 对于细胞的收缩和心脏的跳动至关重要。线粒体和其他细胞。例如，就像细胞中的干细胞一样，它们使我们能够
讲话人（自动字幕未标注）：
intestinal lining to be turned over every 5 to seven days, which is amazing. By the way, >> your whole gut >> your whole gut is turning over every 5 to seven days. The the lining of that of your gut, it is it is amazing. Those stem cells, ATP is not the major demand of those of those cells. They need to completely duplicate themselves constantly every day or less. So their metabolic program is very different from a
肠壁每五到七天就要翻转一次，这真是太神奇了。顺便说一句，>>您的整个肠道>>您的整个肠道每 5 到 7 天就会翻转一次。你肠道的内壁，真是太神奇了。对于那些干细胞来说，ATP 并不是那些细胞的主要需求。他们需要每天或更短时间不断地完全复制自己。所以他们的代谢程序与人类非常不同
讲话人（自动字幕未标注）：
cardiammyasite which just needs to make ATP to a first approximation. They need to make a whole new cell. So we talked about you know the metabolism of of the organism. The metabolism of those cells is very complex because it needs to replicate all the DNA, duplicate it to go into a new cell, duplicate all the proteins, duplicate all the membranes, the lipids, and that needs to happen rapidly. And so that metabolic
Cardiammyasite 只需要使 ATP 达到第一近似值。他们需要制造一个全新的细胞。所以我们谈到了你知道有机体的新陈代谢。这些细胞的新陈代谢非常复杂，因为它需要复制所有 DNA，复制它以进入新细胞，复制所有蛋白质，复制所有膜、脂质，而且这需要快速发生。所以新陈代谢
讲话人（自动字幕未标注）：
wiring is is completely different. And again, the mitochondria are fundamental to that. So those mitochondria are wired in a way that enable them to produce the biomass that's required to make a new cell quite different from the mitochondria of a cardiammyioite. And that diff distinction plays out in virtually all cells in our body, right? Every one of our cells has some particular purpose, some particular function
接线是完全不同的。线粒体对此至关重要。因此，这些线粒体的连接方式使它们能够产生制造新细胞所需的生物量，这与心肌细胞的线粒体完全不同。这种差异实际上存在于我们身体的所有细胞中，对吗？我们的每一个细胞都有一些特定的目的、一些特定的功能
讲话人（自动字幕未标注）：
that it serves uh for the body and the demands of the mitochondria therefore of that cell are different depending on the unique functions and demands of that cell. And so it's a fascinating topic, this diversification of mitochondria. I think again that's something that we're learning about. One of the developments that's really been happening over the last few years, very much a frontier field, is you might imagine
它为身体服务，因此该细胞的线粒体的需求是不同的，具体取决于该细胞的独特功能和需求。因此，线粒体的多样化是一个令人着迷的话题。我再次认为这是我们正在学习的东西。您可能会想象，过去几年中真正发生的发展之一，很大程度上是一个前沿领域
讲话人（自动字幕未标注）：
a cell that has a complex set of demands. There's actually evidence most prominently published recently by Craig Thompson at at Sloan Ketering that showed that in one cell you can have two different kinds of mitochondria that have two different functions and they're distinct in one cell. >> What what's each of them doing? >> Yeah. One of them tends to be more biosynthetic, maybe producing biomass, and one of them
具有一系列复杂需求的细胞。实际上，克雷格·汤普森最近在斯隆·凯特林大学发表的最引人注目的证据表明，在一个细胞中可以有两种不同类型的线粒体，它们具有两种不同的功能，并且它们在一个细胞中是不同的。 >> 他们每个人都在做什么？ >> 是的。其中之一往往更具生物合成性，可能会产生生物质，而其中之一
讲话人（自动字幕未标注）：
tends to be more energy extracting and producing ATP. That's a an overly simplified but generally accurate way of thinking about it. It really emphasizes this unique function of of mitochondria that can be adapted again for the needs of the cell. >> Okay. So, I eat some food and uh that food's absorbed and I get glucose circulating in my bloodstream. I've got some stored energy in the form of glycogen etc. And I'm
往往会提取更多能量并产生 ATP。这是一种过于简化但总体上准确的思考方式。它确实强调了线粒体的这种独特功能，可以再次适应细胞的需要。 >> 好的。所以，我吃了一些食物，呃，食物被吸收了，葡萄糖在我的血液中循环。我以糖原等形式储存了一些能量。
讲话人（自动字幕未标注）：
curious how greedy are the different mitochondria? Is the name of the game that every cell is trying to get as much energy as it can to produce as much ATP as possible or are they communicating and is it energy being allocated in some way that's a little bit more um democratic that's one question then framed within that um I could imagine two scenarios one non mutually exclusive where like the vasculature just
好奇不同的线粒体有多贪婪？游戏的名称是每个细胞都试图获得尽可能多的能量以产生尽可能多的 ATP，或者它们是否在通信，是否以某种更民主的方式分配能量，这是一个问题，然后在这个框架中我可以想象两种情况，一种是非相互排斥的，就像脉管系统一样
讲话人（自动字幕未标注）：
distributes the glucose very well to everything so everybody every cell gets gets access to some of this glucose and and then is just greed needy trying to make as much ATP as possible and the whole system works beautifully. I could also imagine a situation where there's some shuttling to important structures like the brain, you know, like keeping you alive like breathing, heart that there's a prioritization of of
将葡萄糖很好地分配到所有物质中，因此每个人的每个细胞都可以获得一些葡萄糖，然后只是贪婪地需要尝试制造尽可能多的 ATP，整个系统运行良好。我还可以想象一种情况，其中有一些重要结构的穿梭，比如大脑，你知道，就像让你活着，比如呼吸，心脏，有优先级
讲话人（自动字幕未标注）：
organs. I'm talking about under non-stressful conditions. >> So, yes. So, how is energy allocated to cells and then how are cells divvying up the the goods? Yeah, it's a brilliant question and a fascinating area of physiology. As you allude to, when we eat, our digestive system starts extracting the constituents of what we eat. Again, sugars, amino acids, fats from that food that then triggers signals of different
器官。我说的是在没有压力的情况下。 >> 所以，是的。那么，能量是如何分配给细胞的，细胞又是如何分配物质的呢？是的，这是一个很棒的问题，也是一个令人着迷的生理学领域。正如您提到的，当我们吃东西时，我们的消化系统开始提取我们所吃食物的成分。同样，食物中的糖、氨基酸、脂肪会触发不同的信号
讲话人（自动字幕未标注）：
kinds, GLP-1 being one, insulin being another. Those signals then are hormones. They get secreted and they go to many cells throughout the body and that tells each individual cell we just ate. And the implications of that are different from each cell. Some cells don't care. Some cells don't pay attention to that and they just keep on doing what they were doing. Some cells care a lot. Aipocites for example, these are
GLP-1 是一种，胰岛素是另一种。这些信号就是激素。它们被分泌出来，进入全身的许多细胞，并告诉每个细胞我们刚刚吃了什么。每个细胞的含义都不同。有些细胞不在乎。有些细胞不注意这一点，他们只是继续做他们正在做的事情。有些细胞非常关心。例如，Aipocites 是
讲话人（自动字幕未标注）：
the fat cells, the cells that make up our fat tissue. They care a great deal about that. And when they see insulin, what they do is they turn on a protein. They start making a protein that will cause glucose to be taken up into that adiposite, that fat cell. And that glucose will then be converted through a series of chemical reactions into a fat molecule. And then that fat molecule will be stored away in a way that
脂肪细胞，构成我们脂肪组织的细胞。他们非常关心这一点。当他们看到胰岛素时，他们所做的就是打开一种蛋白质。他们开始制造一种蛋白质，这种蛋白质会导致葡萄糖被脂肪细胞吸收。然后，葡萄糖将通过一系列化学反应转化为脂肪分子。然后脂肪分子将以某种方式被储存起来
讲话人（自动字幕未标注）：
is very safe and enabled to be stored for potentially a very long time. And again, it's a beautiful way for the organism to coordinate. I just ate our energy status as an organism, as a body is great. It's very good. So let's squirrel away some of that energy in the form of fat that can be stored in our adiposytes again very safely and can be then used when we go through a period of prolonged fasting which doesn't
非常安全，可以保存很长时间。再说一遍，这是有机体协调的一种美妙方式。我只是吃了我们作为一个有机体的能量状态，因为一个身体是伟大的。非常好。因此，让我们以脂肪的形式储存一些能量，这些能量可以非常安全地再次储存在我们的脂肪细胞中，然后在我们经历一段长时间禁食时可以使用，而这不会影响我们的健康。
讲话人（自动字幕未标注）：
happen for us all that frequently but happened for our ancestors probably much more frequently and those atyposites full of fat from when we ate probably kept our ancestors alive when they went through the periods of prolonged fasting. Insulin has other effects on muscle and and other cells throughout the body that again this is the brilliance of this coordination. The response of different cells to the fed state is
这种情况在我们所有人身上经常发生，但在我们的祖先身上发生的频率可能要高得多，而我们吃东西时产生的那些充满脂肪的异质可能使我们的祖先在经历长期禁食期间得以存活。胰岛素对肌肉和全身其他细胞还有其他影响，这又是这种协调的辉煌之处。不同细胞对进食状态的反应为
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different depending on the the the needs and and functions of that cell. Again, some cells don't care at all. They're going to just go about and do their business. And some cells completely rewire their function depending on the the metabolic state the fed fasted state of the organism. So the picture you just described leads me to conclude that basically every cell obviously knows its job and is not greedily but is
根据该细胞的需求和功能而有所不同。同样，有些细胞根本不在乎。他们将继续做他们的事。有些细胞根据生物体的代谢状态和禁食状态完全重新连接其功能。所以你刚才描述的图片让我得出结论，基本上每个细胞显然都知道自己的工作，并且不是贪婪的，而是
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um diligently fulfilling that role. >> Yeah. And somehow the whole thing is orchestrated so that like we work which I know I think for some people it might be like duh but like just like think about that crazy >> like a liver cell isn't really talking to the brain cell in any kind of direct way about how much glucose it has access to. What you describe makes me really understand for the first time the brilliance of
嗯，努力履行这个角色。 >> 是的。不知何故，整个事情都是精心策划的，就像我们工作一样，我知道我认为对某些人来说这可能就像是废话，但就像想想那个疯狂的>>就像肝细胞并没有真正以任何直接的方式与脑细胞对话它可以获得多少葡萄糖。你的描述让我第一次真正体会到了
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having this hormone signal insulin not just as a shuttle because I think most people we think like insulin sensit most people listen to this podcast or just existed in the world today they're like oh you want to be insulin sensitive you want your cells to recognize this signal but we've never actually talked on this podcast about what exactly that signal is we think about insulin as a shuttle >> but the size of that
拥有这种激素信号胰岛素不仅仅是作为一个航天飞机，因为我认为大多数人我们认为胰岛素敏感大多数人听这个播客或者只是存在于今天的世界上他们就像哦你想要胰岛素敏感你希望你的细胞识别这个信号但我们从来没有在这个播客上真正讨论过这个信号到底是什么我们认为胰岛素作为一个航天飞机>>但它的大小
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signal is saying what's likely to be there and I realize has all sorts of cool implications that can prepare the cell to like oh I'm going to go to work hard now to be the little squirrel that I am of a fat cell and like squirrel away as much as I can or be a brain cells like let's go >> I'm ready to fire action potentials if I need to and some cells like the photo receptors in the eye are just doing that >> eyes
信号说的是那里可能有什么，我意识到有各种各样很酷的含义，可以让细胞做好准备，哦，我现在要努力工作，成为一只小松鼠，我是一个脂肪细胞，尽可能远离松鼠，或者成为一个脑细胞，就像我们走吧>>我已经准备好在需要时激发动作电位，而一些细胞，如眼睛中的光感受器，正在这样做>>眼睛
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closed they're firing eyes open well it's tricky but they're more or less firing it's a not worth going into obviously but in every one of these cells mitochondria are the ones that are essentially going to drive this ATP >> thing right and that seems extremely efficient, too, to just have essentially one major cellular energy source. So, if you could walk us through what happens as glucose gets into the cell and
闭上它们会发射眼睛，睁开很好，这很棘手，但它们或多或少会发射，这显然不值得深入研究，但在每一个细胞中，线粒体都是本质上驱动这种 ATP >> 正常运转的细胞，而且这似乎也非常有效，基本上只有一个主要的细胞能量来源。所以，如果你能告诉我们当葡萄糖进入细胞时会发生什么
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and and really what we've not done ever on this podcast and I I don't think I've heard elsewhere on any podcasts, >> maybe it's out there, but is how you go from ATP to actually the cell being able to perform its roles. Yeah. >> And I realize there's a lot of biochemistry there, but you've worked on some really lynchpin molecules in that pathway that perform very specific roles. And so like maybe we could really
事实上，我们在这个播客中从未做过，我想我在其他任何播客中都没有听到过，>>也许它就在那里，但它是如何从 ATP 转变为真正能够发挥其作用的细胞。是的。 >> 我意识到那里有很多生物化学，但你已经研究了该途径中一些真正关键的分子，这些分子发挥着非常特定的作用。所以也许我们真的可以
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talk about basically gets us from ATP to pyuvate, which might scare some people away, but you'll you'll educate us as to why it's not scary. It's just super cool and why it's so important to have these signals that that aren't just like chemicals. They actually mean something for the cell. Cuz for me, forgive me for going a little long here, but then I'll shut up. I think if people can really internalize this idea
谈论基本上让我们从 ATP 到丙酮酸，这可能会吓跑一些人，但你会告诉我们为什么它并不可怕。这真是太酷了，为什么拥有这些信号如此重要，这些信号不仅仅是化学品。它们实际上对细胞有意义。因为对我来说，请原谅我在这里说得有点长，但我会闭嘴的。我想如果人们真的能够内化这个想法
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that yeah, like hormones go up, hormones go down. Cortisol goes up with stress, it goes down. You wake up, cortisol goes up. Melatonin when you're sleepy. It's not just that it's there, but that the size of the signal says a lot more than just be sleepy. It's saying what once happened is different than what's happening now. It sets a stage for what happens next. And this is really like the verbs of biology that are
是的，就像荷尔蒙上升一样，荷尔蒙也会下降。皮质醇会随着压力而上升，也会随着压力而下降。当你醒来时，皮质醇会上升。困倦时服用褪黑素。不仅是它的存在，而且信号的大小不仅仅说明了困倦。这是说曾经发生的事情与现在发生的事情不同。它为接下来发生的事情奠定了基础。这真的很像生物学中的动词
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harder to communicate even in video. Yeah. >> So, take us from glucose to ATP and ATP to this thing that we call energy. >> Yeah, there's a obviously a lot to unpack there. Glucose is the dominant, let's say, carbohydrate, the dominant sugar that most our cells are consuming. And when glucose is brought into a cell, it goes through again a series of chemical reactions that we call glycolysis. And I I'm going to
即使在视频中也很难沟通。是的。 >> 那么，让我们从葡萄糖转向 ATP，再从 ATP 转向我们称之为能量的东西。 >> 是的，显然有很多东西需要解开。葡萄糖是主要的，比如说碳水化合物，是我们大多数细胞消耗的主要糖。当葡萄糖进入细胞时，它会再次经历一系列我们称之为糖酵解的化学反应。我要去
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simplify because there's obviously this is the subway map of New York. There's a lot of branches going all over the place that we're going to >> go north or south. >> North and south, >> which is pretty much the only direction you can go on the cell. I'm I'm not a New Yorker. I'm kidding. I realize you can go across across the aisle. >> Yeah. Don't insult the New Yorkers anymore. Yeah. >> So glucose comes into a
简化一下，因为显然这是纽约的地铁地图。我们要去的地方有很多分支，>> 向北或向南。 >> 北和南，>> 这几乎是您在牢房上可以前进的唯一方向。我不是纽约人。我在开玩笑。我知道你可以穿过过道。 >> 是的。别再侮辱纽约人了。是的。 >> 所以葡萄糖变成了
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cell, goes through a series of chemical reactions, and you mentioned it gets to pyrovate. That's the end point of glycolysis, this set of chemical reactions. And then pyrovate there's a decision that has to be made by that cell. It can either take that pyrovate into the mitochondria and burn it essentially oxidize it which is essentially burning it combining it with oxygen and that is a very effective way to extract
细胞，经历一系列化学反应，你提到它会发生丙酮酸化。这是糖酵解（这组化学反应）的终点。然后丙酮酸必须由该细胞做出决定。它可以将丙酮酸带入线粒体并燃烧它，本质上是氧化它，这本质上是燃烧它与氧气结合，这是一种非常有效的提取方法
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all the energy that can be extracted from that glucose via pyrovate. >> Tell us a little bit about pyrovate. Yeah. What's the best way to like conceptualize pyuvate for for somebody like me? >> It's an intermediate. It's a midpoint let's say from glucose. Glucose is a sixcarbon molecule complex chemical sixcarbon chemical that gets again chemically modified down to this pyrovate which is as I alluded to in a way
可以通过丙酮酸从葡萄糖中提取的所有能量。 >> 告诉我们一些关于丙酮酸的信息。是的。对于像我这样的人来说，理解丙酮酸的最佳方式是什么？ >> 这是一个中间体。比方说，这是葡萄糖的中点。葡萄糖是一种六碳分子复杂的化学六碳化学物质，它再次被化学修饰成这种丙酮酸盐，正如我在某种程度上提到的那样
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kind of a pivot point >> in the metabolism of that glucose. And the reason why we became really fascinated with pyrovate is because of that bifurcation that happens. Pyrovate can either be again taken into mitochondria and burned and that's very effective for generating ATP for extracting all the energy that can be extracted and that's what cardiammyioytes for example really love to do take that everything they can
这是葡萄糖代谢的一个关键点>>。我们之所以对丙酮酸盐如此着迷，是因为这种分歧的发生。丙酮酸可以再次被摄入线粒体并燃烧，这对于生成 ATP 非常有效，可以提取所有可以提取的能量，这就是心肌细胞真正喜欢做的事情，尽其所能
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from the circulation burn it make ATP keep our heart pumping and again other cells on the other hand don't do that they don't need as much ATP so those intestinal stem cells that I talked about that are the factory in a Okay, that's enabling the repopulation of our gut lining every week. They do something different with that pyrovate. They instead of burning it turn that pyrovate and other molecules intermediates in
从循环燃烧中，它使 ATP 保持我们的心脏跳动，而另一方面，其他细胞则不会这样做，它们不需要那么多的 ATP，所以我谈到的那些肠道干细胞是工厂，好吧，这使得我们的肠道内壁每周都能重新繁殖。他们用丙酮酸做了一些不同的事情。它们不是燃烧而是将丙酮酸盐和其他分子中间体转化为
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glycolysis into biomass into the stuff that will enable that one cell to duplicate itself. And I've become totally fascinated with this bifurcation. Food can either be converted to energy or it can be converted to biomass. I think that's maybe a bit overly simplistic, but I think a good baseline way to think about the what we get out of the food that we eat. Energy or building blocks that can be used to make a new
糖酵解转化为生物质，转化为使细胞能够自我复制的物质。我对这种分歧完全着迷。食物可以转化为能量，也可以转化为生物质。我认为这可能有点过于简单化，但我认为这是一个很好的基线方法来思考我们从我们吃的食物中得到什么。可用于制造新产品的能源或积木
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cell to repair a cell that's been damaged for a B cell and immune cell that are the ones that make antibodies. making a bunch of antibodies, which an activated B cell needs to do. That's a lot of stuff that needs to be made. That requires that B cell to have a lot of amino acids that can be turned into proteins, which are antibodies are proteins. And and and that again, that's a very important part of our immune
修复受损细胞的 B 细胞和产生抗体的免疫细胞。产生一堆抗体，这是激活的 B 细胞需要做的。有很多东西需要制作。这就要求 B 细胞有很多氨基酸可以转化成蛋白质，抗体就是蛋白质。再说一遍，这是我们免疫的一个非常重要的部分
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system that keeps us protected from invaders that might otherwise kill us. And so that that distinction that lands at the point of pyrovate I think is a is a super fascinating pivot point in metabolism that I think many of us are fascinated by exactly how the cell >> organizes itself to make the right resource allocation decisions. You know every one of our cells is all every second of every day is making resource
保护我们免受入侵者侵害的系统，否则这些入侵者可能会杀死我们。因此，我认为丙酮酸点上的区别是新陈代谢中一个超级迷人的枢轴点，我认为我们很多人都对细胞如何组织自身以做出正确的资源分配决策着迷。你知道我们的每一个细胞每一天的每一秒都在制造资源
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allocation decisions. What does it do with the stuff that it has? And and this is one that I think is really fascinating. >> So we are probably like seven I'm insulting the cell biologists but probably seven steps away from sandwich. So sandwich goes in the mouth into the gut gets absorbed right we get glucose. Glucose gets into the cell. We got some important biochemistry that you know is in this uh ATP generation
分配决定。它对它所拥有的东西有什么作用？我认为这是非常令人着迷的。 >> 所以我们可能有七步之遥（我在侮辱细胞生物学家），但距离三明治可能还有七步之遥。因此，三明治进入口腔后就会被肠道吸收，我们就会得到葡萄糖。葡萄糖进入细胞。我们得到了一些重要的生物化学，你知道这些是在这个呃 ATP 一代中
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pathway and we get to this like key node that you're describing as pyuvate and pyuvate is either going to say let's make more you called it biomass but stuff of cells. >> Yeah. >> So we're like you have lumber arriving maybe might be a decent enough analogy. You're either going to use it to build more house or you're going to burn it >> for heat energy. >> Great analogy. Um, and let's look make a add a condition
途径，我们到达了这个关键节点，你将其描述为丙酮酸，而丙酮酸要么会说让我们制造更多你称之为生物量的东西，但细胞的东西。 >> 是的。 >> 所以我们就像你有木材到达也许是一个足够恰当的类比。你要么用它来建造更多的房子，要么将它燃烧>>以获取热能。 >> 很好的类比。嗯，让我们看看添加一个条件
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where you need to burn some of that lumber for heat energy to keep the construction project going. >> Exactly. >> Okay. So, we're at this key bifurcation, this key split point. Is it just as metabolically demanding for a cell to use pyuvate to keep itself going like a cardomyioite versus making biomass or is one more costly? I'm thinking again as you beautifully pointed out at the beginning about thinking about that
您需要燃烧一些木材来获取热能，以维持建设项目的进行。 >> 正是如此。 >> 好的。所以，我们正处于这个关键的分叉点，这个关键的分裂点。对于细胞来说，使用丙酮酸来保持自身运转与制造生物质相比，是否与使用丙酮酸一样需要更高的代谢要求，还是成本更高？我又开始思考了，就像你一开始就漂亮地指出的那样
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our metabolism as a whole body as a person is is the sum total of all these these things is it equivalent in terms of like >> how much sandwich relatively speaking is going into maintaining us and rebuilding us what you call biomass what I'm calling building you know allocating lumber for the for the house itself >> versus to uh fuel the fire so to speak >> that's hard math to do there's a lot of nuance rough
作为一个人，我们整个身体的新陈代谢是所有这些东西的总和，它相当于>>相对而言，有多少三明治用于维持我们和重建我们，你所说的生物质，我所说的建筑，你知道为房子本身分配木材>>与呃可以说是生火>>这是很难做的数学，有很多细微差别。
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percentages. I won't hold you to it. >> Yeah. No, I mean one way to think about that, many of us are probably unfortunately aware of PET imaging, right? This is this is something that happens that's often used to diagnose cancer emission tomography. >> An FDG PET, which is the most common form of PET, is basically you're giving cells a form of glucose that can then be visualized with this PET scan that many people
百分比。我不会让你坚持下去。 >> 是的。不，我的意思是从一种角度考虑，不幸的是我们中的许多人可能都知道 PET 成像，对吗？这是经常用于诊断癌症发射断层扫描的情况。 >> FDG PET 是 PET 的最常见形式，基本上是为细胞提供一种葡萄糖，然后可以通过许多人的 PET 扫描进行可视化
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are aware of. And the reason we do that is because tumors take up a lot of glucose and FDG PET is fluoroxy glucose. This is a a labeled version of glucose. So the reason we do FDG PET is to see the cells where in the body is taking up a lot of glucose and tumors take up a lot of glucose. So FDG PET is used to diagnose cancer frequently very effectively. So that is one metric for this. A cancer cell is again a cell
都知道。我们这样做的原因是因为肿瘤会吸收大量葡萄糖，而 FDG PET 是氟氧葡萄糖。这是葡萄糖的标记版本。因此，我们进行 FDG PET 的原因是观察体内细胞吸收大量葡萄糖以及肿瘤吸收大量葡萄糖的情况。因此 FDG PET 经常被用来非常有效地诊断癌症。这是衡量这一点的一个指标。癌细胞又是细胞
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that is making a resource allocation decision all the time. But in the context of of that cell when it transforms into a cancer cell that resource allocation becomes very much about building more cells. That's why a tumor is a tumor is because that one cell that was the first bad actor decided instead of doing the thing it was supposed to be doing decided to duplicate itself and duplicate itself again and build a
那就是一直在做出资源分配决策。但在该细胞转变为癌细胞的情况下，资源分配就变得非常重要的是建立更多的细胞。这就是为什么肿瘤之所以是肿瘤，是因为作为第一个坏演员的一个细胞决定不做它应该做的事情，而是决定复制自己并再次复制自己并构建一个
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cluster of cells that then become a tumor. >> Okay. I have a pseudo philosophical question but it's really a scientific medical question about tumors. Bacteria have the opportunity to hijack genomes of cells. viruses certainly probably the the easiest example for people to understand is like a herpes virus like HSV1 or something which lives on neurons >> doesn't kill the neuron which is convenient for the virus >>
然后变成肿瘤的细胞簇。 >> 好的。我有一个伪哲学问题，但这实际上是一个关于肿瘤的科学医学问题。细菌有机会劫持细胞的基因组。病毒当然可能是人们理解的最简单的例子，就像 HSV1 这样的疱疹病毒或一些生活在神经元上的东西>>不会杀死对病毒来说很方便的神经元>>
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right because if it killed the neuron it too would die because if the neuron is expressing that virus it's hijacked the genome >> so this earlier I was saying like viruses have their own quote unquote intelligence >> like stay alive but keep the host alive too and transmit and in the case of rabies it's the most easiest one to conceptualize like impact areas of the brain that trigger aggression would that trigger >>
是的，因为如果它杀死了神经元，它也会死亡，因为如果神经元表达该病毒，它就会劫持基因组>>所以早些时候我说就像病毒有自己引用的情报>>就像保持活力但让宿主也活着并传播，在狂犬病的情况下，这是最容易概念化的，就像触发攻击的大脑影响区域会触发>>
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right >> biting and and people have speculated like does the virus know that it's doing this like probably not right doesn't they're not brains but pretty impressive level of quote unquote >> uh adaptive behavior and intelligence >> I think of cancer as just a bad thing all around right that these cells are greedy they're taking glucose they're making more of themselves it's cell turnover gone arry tumor gets big,
对>>咬人，人们推测病毒是否知道它正在这样做，这可能不对，不是吗？它们不是大脑，但引用不引用的水平相当令人印象深刻>>呃适应性行为和智力>>我认为癌症只是一件坏事，这些细胞很贪婪，它们正在服用葡萄糖，它们正在制造更多的自身，细胞更新消失了，肿瘤变大了，
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it starts to encroach on other tissues, metastasize, boom, you kill the host. >> That's not a great strategy from the perspective of the tumor. So, it obviously isn't thinking about its long-term outcome in any kind of adaptive way. >> But has anyone ever looked at tumors in the same way that we think about viruses? Like the logic there is the same. >> Yeah. >> Except it it seems that their goal is to kill the
它开始侵入其他组织，转移，轰隆隆，你杀死了宿主。 >> 从肿瘤的角度来看，这不是一个好的策略。因此，它显然没有以任何适应性方式考虑其长期结果。 >> 但是有人曾经像我们看待病毒一样看待肿瘤吗？就像逻辑是一样的。 >> 是的。 >> 但他们的目标似乎是杀死
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organism. I'm not trying to anthropomorphize about cells and cellular processes, but I think is there a a potential set of answers about how to deal with tumors and and think about cancer that could be borrowed from any of those other examples or am I or am I going down the wrong path? >> Yeah, it's an it's an interesting question. You know, viruses and bacteria, similar to how you were describing viruses, some of
生物。我并不是想将细胞和细胞过程拟人化，但我认为是否有一套关于如何处理肿瘤和思考癌症的潜在答案，可以从任何其他例子中借用，或者我是否走错了路？ >> 是的，这是一个有趣的问题。你知道，病毒和细菌，就像你描述的病毒一样，其中一些
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the same principles apply to bacteria in you know, parasitic bacteria. Viruses, as you allude to, their goal that, you know, if you do want to anthropomorphize them, their goal is to propagate, right? They are under evolutionary pressure. The way that that virus survives is to make more of itself, go infect another organism and have that other organism make a bunch of additional viruses that will then go and infect
同样的原理也适用于你知道的细菌，即寄生细菌。正如你提到的，病毒的目标是传播，你知道，如果你确实想将它们拟人化，它们的目标就是传播，对吗？他们面临着进化的压力。该病毒生存的方式是制造更多的自身，感染另一个有机体，并让另一个有机体制造一堆额外的病毒，然后再感染
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another organism, right? That is the evolutionary game >> and that's what viruses do. And they're very good at it. And you described some really interesting biology where viruses will actually affect the behavior of the host to make them better at getting into the next host. It's amazing. >> I wish we had a better language for this thing because intelligence is not really it because it's not of brains, >> but it's
另一种有机体，对吧？这就是进化游戏>>，这就是病毒所做的。他们非常擅长。你描述了一些非常有趣的生物学，其中病毒实际上会影响宿主的行为，使它们更好地进入下一个宿主。太棒了。 >> 我希望我们有一种更好的语言来描述这件事，因为智力并不是真正的智力，因为它不是大脑，>> 但它是
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this adaptive logic. >> Yeah, that's a good uh phrase for it, adaptive logic that enables the survival and propagation of that virus. And and this is how evolution works, of course. If that virus had a mutation that made it better able to do that, that virus then would infect better >> and it would get into hosts better, propagate better, and it would eventually take over the population of that virus. That is the
这种自适应逻辑。 >> 是的，这是一个很好的短语，适应性逻辑使病毒得以生存和传播。当然，这就是进化的运作方式。如果该病毒具有使其能够更好地做到这一点的突变，那么该病毒就会更好地感染>>并且它会更好地进入宿主，更好地传播，并且最终会接管该病毒的种群。那就是
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process of evolution. And I think again it makes intuitive sense. You know, you asked about cancer. Cancer is obviously fundamentally different in one key way. If I get a virus and I come in here and we're sitting across the table and I'm hacking and whatever and I spew across the table at you, you might get the virus, >> get sick, build a bunch of additional virus, and then you give it to co-workers and that's
进化的过程。我再次认为这具有直观意义。你知道，你问的是癌症。癌症显然在一个关键方面有着根本的不同。如果我感染了病毒，我来到这里，我们坐在桌子对面，我在黑客攻击什么的，然后我向你喷洒在桌子上，你可能会感染病毒，>>生病，建立一堆额外的病毒，然后你把它给同事，那就是
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viral propagation, which we all sadly know about. There's very little evidence that cancer is infectious. >> What about Tasmanian devils? >> You know about this, right? >> No, I don't know about this. >> Okay, I don't know if this held up, but there was this idea for a while. Someone will tell us in the comments. This is what's fun about doing this on the internet. >> That Tasmanian devils fight and that there's
病毒传播，我们都遗憾地知道这一点。几乎没有证据表明癌症具有传染性。 >> 塔斯马尼亚恶魔怎么样？ >> 你知道这件事，对吗？ >> 不，我不知道这个。 >> 好吧，我不知道这是否成立，但这个想法已经有一段时间了。会有人在评论里告诉我们。这就是在互联网上做这件事的乐趣所在。 >> 塔斯马尼亚袋獾之间的战斗
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wound induced propagation of cancers. These very disturbing as an animal lover, you know, very disturbing images of these cute little animals with these little teeth. They're they have a viciousness to them and they have these like tumors growing at the at wound sites and it turns out those are cancer. So there's somehow like >> fighting and wounds and viral, it might it might be bacterial. I don't know. That's
伤口诱发癌症扩散。作为一个动物爱好者，这些非常令人不安的图像，这些带有小牙齿的可爱小动物的图像非常令人不安。他们对他们怀有恶意，他们的伤口处长有类似肿瘤的东西，结果证明这些是癌症。所以有一些类似>>打斗、伤口和病毒，也可能是细菌。我不知道。那是
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outside my expertise, >> but there was this idea that you that they could transmit cancers to one another through fighting. >> Interesting. >> Which I thought was sad but fascinating nonetheless. And Australia is a weird place, you know. >> A lot of stuff happens. >> I mean, the world's upside down there, so after all. No. Um but but right, you're right. In general, yeah, we don't actually think that um people are
在我的专业知识之外，>>但有一种想法是，他们可以通过战斗相互传播癌症。 >> 有趣。 >> 我觉得这很悲伤，但仍然很有趣。你知道，澳大利亚是一个奇怪的地方。 >> 发生了很多事情。 >> 我的意思是，世界毕竟是颠倒的。不，嗯，但是对，你是对的。总的来说，是的，我们实际上并不认为嗯人们是
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catching cancers from one another. >> So when you think about the evolution of a cancer, the scope of that evolution is different, right? The scope of that evolution of a a cell in me >> is limited to me. >> Cancer cells undergo evolution in the exact same way. You know, if one cell in my body starts propagating, it acquires a mutation that enables it to divide and divide faster and maybe it, you know, get out from
互相传染癌症。 >> 所以当你思考癌症的进化时，进化的范围是不同的，对吗？我体内的一个细胞的进化范围>>仅限于我自己。 >> 癌细胞以完全相同的方式经历进化。你知道，如果我体内的一个细胞开始繁殖，它就会获得一种突变，使其能够分裂得更快，也许它，你知道，会从
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underneath the limits that are being placed upon it by the immune system and by other systems that control propagation of cells in the body. It can then divide and divide again. And that's basically the continuous process of cancer development is the acquisition of mutations that make that cell better able to evade the immune system, to duplicate itself, evade um the the problems that would come with DNA damage,
在免疫系统和其他控制体内细胞增殖的系统对其施加的限制之下。然后它可以分裂并再次分裂。基本上，癌症发展的连续过程就是获得突变，使细胞能够更好地逃避免疫系统，自我复制，逃避 DNA 损伤带来的问题，
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which many cancers have, and to continue to make it make cells that survive. And that is in a way an evolutionary process playing out at the level of individual cells. But how that interacts with the host is obviously different because again a virus has this sort of evolutionary drive to get from one organism to to another to another to enable its propagation. Cancer you isn't fueled by the same motivations let's
许多癌症都具有这种能力，并继续使其使细胞能够存活。这在某种程度上是在单个细胞水平上进行的进化过程。但它与宿主的相互作用方式明显不同，因为病毒同样具有这种进化驱动力，从一种生物体到另一种生物体，再到另一种生物体，以实现其传播。巨蟹座，你没有同样的动机，让我们
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say because again as far as we're aware that very rarely if almost never happens to get from one organism to another. And so the motivations are different, but the evolutionary process underlying it, it's the same principles at play in both. >> I'd like to take a quick break and acknowledge our sponsor, AG1. AG1 just launched their newest formulation called AG1 Pro. And right now, you can get an extra 20% off your
再说一次，因为据我们所知，很少甚至几乎从未发生过从一种生物体传播到另一种生物体的情况。因此，动机是不同的，但其背后的进化过程，两者的原理是相同的。 >> 我想稍微休息一下并感谢我们的赞助商 AG1。 AG1 刚刚推出了名为 AG1 Pro 的最新配方。现在，您可以额外享受 20% 的折扣
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first subscription. AG1 takes the clinically backed AG1 formula, which is a blend of vitamins, minerals, probiotics, and adaptogens, and adds three important new ingredients. Creatine monohydrate, calcium HMBB, and zinc carnosine. It has 5 g of creatine monohydrate to support muscle strength and performance along with brain health, calcium HMBB to support muscle recovery and reduce muscle breakdown, and zinc
第一次订阅。 AG1 采用经过临床支持的 AG1 配方，该配方混合了维生素、矿物质、益生菌和适应原，并添加了三种重要的新成分。一水肌酸、HMBB 钙和肌肽锌。它含有 5 克一水肌酸，可支持肌肉力量和表现以及大脑健康；HMBB 钙可支持肌肉恢复并减少肌肉分解；以及锌
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carnosine to support and improve the lining of your gut. Some of these ingredients I personally was already taking separate from the AG1 formula. So, it's great to see all three of them now in the new AG1 Pro. As you may know, I've been taking AG1 every single day for about 14 years now. That means I discovered it and started taking it daily long before I even knew what a podcast was. I continue to take it and back
肌肽支持和改善肠道内壁。我个人已经将其中一些成分与 AG1 配方分开服用。因此，很高兴看到这三者现在都出现在新款 AG1 Pro 中。如您所知，我每天服用 AG1 已有大约 14 年了。这意味着我早在知道播客是什么之前就发现了它并开始每天服用它。我继续把它拿回来
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it here on the podcast because it is an excellent formula. And it's now even better with the AG1 Pro formula. For a limited time, you can get an extra 20% off your first subscription to AG1 Pro by going to drinkag1.com/huberman and using the code backtoine. So that's with the numeral 2 back numeral 2 routine. Just go to drinkag1.com/huberman. Today's episode is also brought to us by eight. Eightle makes smart
它出现在播客上，因为它是一个很好的公式。现在，有了 AG1 Pro 配方，效果会更好。在有限的时间内，您可以通过访问 Drinkag1.com/huberman 并使用代码 backtoine 获得首次订阅 AG1 Pro 的额外 20% 折扣。这就是数字 2 后面的数字 2 例程。只需访问 Drinkag1.com/huberman。今天的节目也是八位给我们带来的。八使聪明
讲话人（自动字幕未标注）：
mattress covers with cooling, heating, and sleep tracking capacity. One of the best ways to ensure you get a great night's sleep is to make sure that the temperature of your sleeping environment is correct. And that's because in order to fall asleep and stay deeply asleep, your body temperature actually has to drop by about 1 to 3°. And in order to wake up feeling refreshed and energized, your body temperature
床垫套具有冷却、加热和睡眠跟踪功能。确保您睡个好觉的最佳方法之一是确保睡眠环境的温度正确。这是因为为了入睡并保持深度睡眠，您的体温实际上必须下降约 1 至 3°。为了让您醒来时感觉神清气爽、精力充沛，您的体温
讲话人（自动字幕未标注）：
actually has to increase by about 1 to 3°. Eight automatically regulates the temperature of your bed throughout the night according to your unique needs. I've been sleeping on an eightle mattress cover for nearly 5 years now, and it has completely transformed and improved the quality of my sleep. The latest eight model is the pod 5. This is what I'm now sleeping on, and I absolutely love it. It has so many
实际上必须增加约 1 至 3°。八号可根据您的独特需求自动调节整个晚上的床温。我已经睡在八层床罩上近五年了，它彻底改变并改善了我的睡眠质量。最新的 8 款型号是 pod 5。这就是我现在睡觉的地方，我非常喜欢它。它有这么多
讲话人（自动字幕未标注）：
incredible features. For instance, the Pod 5 has a feature called autopilot, which is an AI engine that learns your sleep patterns and then adjusts the temperature of your sleeping environment across different sleep stages. It'll even elevate your head if you're snoring, and it makes other shifts to optimize your sleep. If you'd like to try eight, go to eight.com/huberman to get up to $350 off the new Pod 5.
令人难以置信的功能。例如，Pod 5 有一个名为“自动驾驶”的功能，这是一个人工智能引擎，可以学习你的睡眠模式，然后在不同的睡眠阶段调整你的睡眠环境温度。如果您打鼾，它甚至会抬高您的头部，并进行其他转换以优化您的睡眠。如果您想尝试 8 台，请访问 even.com/huberman，新款 Pod 5 最高可享受 350 美元优惠。
讲话人（自动字幕未标注）：
Eightlee ships to many countries worldwide including Mexico and the UAE. Again, that's eight.com/huberman to save up to $350. I'll take us down one more estuary, then we are actually going to talk about mitochondria and pyuvate again and your contributions to this critical node of where pyuvate puts its efforts building more stuff of the cell or using energy. Anytime I have a serious cell biologist, which isn't that
Augustlee 向世界各地的许多国家发货，包括墨西哥和阿联酋。同样，访问 8.com/huberman 最多可节省 350 美元。我将带我们再下一个河口，然后我们实际上将再次讨论线粒体和丙酮酸，以及您对丙酮酸努力构建更多细胞物质或使用能量这一关键节点的贡献。任何时候我都有一位严肃的细胞生物学家，这不是那样的
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often on this podcast, or somebody who thinks about the pieces that make up us, I try and ask this. I'm bothered by this one thing I heard once, which is that like it's so easy to think about evolution. It's like, okay, we're all adaptively trying to make more of ourselves, care for our young, and go forward. That's like what every spe every you know, mamalian species does. That all makes sense until I learned about
我经常在这个播客上，或者在思考我们的组成部分的人中，尝试问这个问题。我曾经听到过一件事，这让我感到困扰，那就是思考进化似乎很容易。就像，好吧，我们都在适应性地努力让自己变得更好，照顾我们的年轻人，然后继续前进。这就像你所知道的哺乳动物所做的那样。这一切都是有道理的，直到我了解到
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the gut microbiome from my colleague Justin Sonnenberg and he said you know every time you shake hands like we exchange microbiome today >> and we're sharing in the air and skin we shook hands you see and like there is this one model of like all of this that's very purely biological that we are just shuttles for the microbiota >> and everything that we're doing like building electric cars and uh holding uh debates
我的同事贾斯汀·索南伯格 (Justin Sonnenberg) 提供的肠道微生物组，他说每次握手时都知道，就像我们今天交换微生物组一样 >> 我们在空气和皮肤中分享我们握手时看到的所有这些，这是非常纯粹的生物学模型，我们只是微生物群的穿梭机 >> 以及我们所做的一切，例如制造电动汽车和呃举行呃辩论
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and protests and um sending kids to school and all of that we think is about us but the microbiota are just like they've hijacked this process and like they're not sitting there going these [laughter] humans they think this is all about them and we're just trying to spread and make sure that we continue and maybe long after they're gone we're just going to keep going and I can't poke any holes in this it's like too
抗议，嗯，送孩子上学，所有这些我们认为都与我们有关，但微生物群就像他们劫持了这个过程，就像他们没有坐在那里去这些[笑声]人类一样，他们认为这都是关于他们的，我们只是试图传播并确保我们继续下去，也许在他们离开很久之后，我们只会继续前进，我也无法在这方面戳任何漏洞，就像
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good a theory but I keep hoping somebody's going to tell me at least from a purely biological perspective that like that's not true but it kind of scares me every once in a while I think Maybe I'm just a bunch of micro biota shuttle just the vehicle. >> We're just a shuttle. But we got this brain which is very convenient for them, right? Because it makes me want to go out and do things and I think about failures and
很好的理论，但我一直希望有人至少从纯粹的生物学角度告诉我，这不是真的，但它时不时地让我感到害怕，我想也许我只是一群穿梭于交通工具的微生物群。 >> 我们只是一辆班车。但我们有这个大脑，这对他们来说非常方便，对吗？因为它让我想要出去做事，让我思考失败和失败
01:00:00
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successes and how I want to do better and what I want to do at different stages and like maybe it's just all about them getting as far and wide as they can. >> Well, unfortunately, Andrew, I'm not sure I'm going to be able to provide you the concrete proof that that's not true. It's a it's a fascinating >> kind of eerie, right? >> Yeah, very eerie. We definitely don't like to see think of ourselves as anything other
成功以及我想如何做得更好以及我在不同阶段想做什么，也许这只是他们尽可能走得更远和更广。 >> 不幸的是，安德鲁，我不确定我是否能够向您提供具体证据证明这不是真的。这是一种令人着迷的>>有点怪异，对吧？ >> 是的，非常诡异。我们绝对不喜欢看到自己被视为其他人
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than the pinnacle of evolution and the reason for everything, >> right? >> But there's no question to to your point, the microbiome are the bacteria that live in our gut and on our skin, they're being driven by the same evolutionary pressures that we've been talking about for viruses and for us. They're trying to propagate themselves and fill the niche that they live in, fill the little chunk of of the universe that
比进化的顶峰和一切的原因，>>对吧？ >> 但毫无疑问，你的观点是，微生物群是生活在我们肠道和皮肤上的细菌，它们受到我们一直在谈论的病毒和我们相同的进化压力的驱动。他们试图传播自己并填补他们所生活的空位，填补宇宙中的一小部分
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they live in and do it better than their com their competing neighbors. And if they can do that, then their genome is going to get passed on and again and again. And it's fascinating to think about the role that we play for them and they play for us. This is a phenomenon that's been known for a long time, but I think the implications of the microbiome is something that really has only been, I think, experimentally
他们的生活比他们的竞争邻居做得更好。如果他们能做到这一点，那么他们的基因组就会一次又一次地传承下去。想想我们为他们扮演的角色以及他们为我们扮演的角色是很有趣的。这是一种早已为人所知的现象，但我认为微生物组的影响实际上只是通过实验得到的。
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dealt with in a really serious way in the recent decade or so. And I think we're still learning about the implications, but there's no question that they're big. Tell us about MPC 1 and 2. I'm asking about biochemical steps and a key process of energy production and and allocation. And normally when people hear acronyms, they don't understand. and they kind oh my goodness like what are we doing here? But like I
近十年来，我们以非常严肃的方式进行了处理。我认为我们仍在了解其影响，但毫无疑问它们的影响很大。请告诉我们 MPC 1 和 2。我问的是生化步骤以及能源生产和分配的关键过程。通常，当人们听到缩写词时，他们不理解。他们很友善，天哪，就像我们在这里做什么？但就像我
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think it's so important that people understand like this business of us this metabolism having energy whether we're young or old have a lot of it or less of it healthy or dealing with cancer like this is a key node and what I want to know truly is how do you actually discover something like this because and this is where I think we we can really illustrate the scientific process in a way that like most people just
我认为，让人们了解我们的新陈代谢是非常重要的，无论我们是年轻还是年老，都有能量，无论我们年轻还是年老，都有很多或更少的能量，或者像这样处理癌症，这是一个关键节点，我真正想知道的是，你如何真正发现这样的东西，因为这就是我认为我们可以像大多数人那样真正说明科学过程的地方。
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don't understand. You need cells first of all. You need to be able to find the mic mitochondria. You need to be able to know what's ATP and what's pyuvate. And then you know they're going to two different pathways cuz someone else said that and you can observe it down a microscope. >> Yeah. >> But then how do you find this thing and then tell us what it's doing perhaps or tell us what it's doing. But I think it
不明白。首先你需要细胞。您需要能够找到麦克风线粒体。您需要能够知道什么是 ATP 和什么是丙酮酸。然后你知道他们会走两条不同的路，因为其他人这么说过，你可以在显微镜下观察它。 >> 是的。 >> 但是你如何找到这个东西，然后告诉我们它在做什么，或者告诉我们它在做什么。但我认为
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would be very useful for people to get a picture of how this is done because we hear this stuff like oh this molecule MC and people go oh is there a peptide for that? It's like hold off. Let's think about how we come to understand these these essential aspects of oursel I think would be so useful. >> I appreciate you asking about that. It allows me to reminisce a little bit about the process of discovering that
对于人们了解这是如何完成的来说非常有用，因为我们听到这样的东西，比如哦这个分子 MC，人们会说哦，有肽吗？这就像拖延。让我们思考一下我们如何理解我们自己的这些基本方面，我认为这会非常有用。 >> 感谢您提出这个问题。它让我回忆起发现这一点的过程
讲话人（自动字幕未标注）：
which was you know a fun time in my career and was fueled by the brilliant people in the lab that did it. So MPC this is a case where the acronym actually makes sense. It's the mitochondrial pyrovate carrier. So you don't have to be a scientist. >> Uh we did not name it. that was it was named before. I'll I'll tell you that one story cuz I don't like acronyms that aren't informative. >> MPC, >> aptly named >> is the
你知道，那是我职业生涯中一段有趣的时光，实验室里那些才华横溢的人为我提供了动力。因此，MPC 在这种情况下，缩写词实际上是有意义的。它是线粒体丙酮酸载体。所以你不必成为一名科学家。 >> 呃，我们没有命名它。那是它之前被命名的。我会告诉你一个故事，因为我不喜欢没有信息的首字母缩略词。 >> MPC，>> 恰当地命名>> 是
讲话人（自动字幕未标注）：
carrier >> that enables pyrovate to get into the mitochondria. Mitochondrial pyrovate carrier. That's what it does. Sits in the mitochondria and basically provides a very specific hole in the membrane to enable pyrovate to get in so that it can then be burned by the mitochondria to again extract all the energy to make ATP. That's that's basically what it does. The history of this is really interesting. It's been
载体>>使丙酮酸能够进入线粒体。线粒体丙酮酸载体。这就是它的作用。位于线粒体中，基本上在膜上提供了一个非常特殊的孔，使丙酮酸能够进入，然后它可以被线粒体燃烧，再次提取所有能量来制造 ATP。这基本上就是它的作用。这件事的历史真的很有趣。它已经
讲话人（自动字幕未标注）：
known for 60 or 70 years that mitochondria must have a carrier to enable pyrovate to get in. But it was not identified what that protein was, how it worked. And fast forward to 2008 or nine or so, and our laboratory had just recently become again fascinated with mitochondria. I would say the motivating piece of of information that convinced us to start working on mitochondria was the realization that many of the
60 或 70 年前人们就知道线粒体必须有一个载体才能使丙酮酸进入。但人们并不清楚这种蛋白质是什么以及它如何发挥作用。快进到 2008 年或九年左右，我们的实验室最近才再次对线粒体着迷。我想说，说服我们开始研究线粒体的激励信息是我们认识到许多
讲话人（自动字幕未标注）：
proteins that make up mitochondria that do the stuff that mitochondria do we don't know what their functions are and that suggested that this organel powerhouse of the cell we kind of I at least felt like we knew a lot about what mitochondria do there's mysteries there that we don't have answers for. And so we started just taking some of these proteins that we know are in mitochondria, we don't know what they do,
组成线粒体的蛋白质可以完成线粒体所做的事情，我们不知道它们的功能是什么，这表明我们至少觉得我们对线粒体的功能了解很多，其中存在着我们无法解答的谜团。所以我们开始只提取一些我们知道存在于线粒体中的蛋白质，但我们不知道它们的作用，
讲话人（自动字幕未标注）：
and trying to figure out what they do. And two of those turned out to be MPC1 and MPC2. Way back when I I observed and was taught, I didn't do a ton of this, that like if you want to figure out what proteins are in a cell, you get a bunch of those cells, which you can do >> and then you >> you kind of grind them up and then you run them through a bunch of columns and like literally tubes. >> Yeah. >> And those tubes
并试图弄清楚他们在做什么。其中两个是 MPC1 和 MPC2。早在我观察并被教导时，我并没有做很多这样的事情，就像如果你想弄清楚细胞中含有什么蛋白质，你会得到一堆这些细胞，你可以这样做>>然后你>>你将它们磨碎，然后你将它们穿过一堆柱子，就像字面上的管子一样。 >> 是的。 >> 还有那些管子
讲话人（自动字幕未标注）：
have filters that either let big, less big, small, or very small things through, what we call fractionation, right? And then you kind of test the the different stuff that comes through for its ability to do something in some sort of cell. It's like how did you actually find MPC2? Was it done by like >> sort of hardcore what we call hardcore biochemical purification? That was kind of the old way of doing it. Or well,
有过滤器可以让大的、不太大的、小的或非常小的东西通过，我们称之为分馏，对吗？然后你测试不同的东西在某种细胞中做某事的能力。就像你是如何找到 MPC2 的？它是通过类似 >> 的硬核（我们称之为硬核生化净化）来完成的吗？这是一种古老的做法。或者好吧，
讲话人（自动字幕未标注）：
let me ask this. Do we know the total number >> of proteins in the in a given human heart cell? >> I think we know. Yeah, I think >> we know everything that's in a heart cell. I think we know all the proteins in a heart cell. Again, you can get into the nuances of slightly modified versions, but we know the proteins because they are encoded by our genome, right? We know the human genome that's been sequenced. We
让我问一下。我们是否知道特定人类心脏细胞中蛋白质的总数>>？ >> 我想我们知道。是的，我想>>我们知道心脏细胞中的一切。我认为我们知道心脏细胞中的所有蛋白质。同样，您可以了解稍微修改版本的细微差别，但我们知道这些蛋白质，因为它们是由我们的基因组编码的，对吗？我们知道已被测序的人类基因组。我们
讲话人（自动字幕未标注）：
know what that is, >> but we don't know that everything that's expressed in a given cell. That's right. >> That that's true. And there there are some very interesting features there. >> Can I sorry, I'm interrupting on purpose. 20 years ago, could you say what you just said >> with much less confidence that I than I can now? say heart cell, but we don't actually know all the all the bits in it. But now we do. >> Now
知道那是什么，>>但我们不知道给定单元格中表达的所有内容。这是正确的。 >> 确实如此。那里有一些非常有趣的功能。 >> 抱歉，我是故意打扰的。 20 年前，你能说你刚才说的话吗>>我的信心比现在低得多吗？比如说心脏细胞，但我们实际上并不知道其中的所有部分。但现在我们做到了。 >> 现在
讲话人（自动字幕未标注）：
I think we we know >> essentially everything. Again, there's going to be subtle nuances that we don't know, but I think we know almost everything. >> That's good. >> Doesn't mean we know what all those things do. And that's maybe the frontier for the biochemistry frontier for the next generation of scientists to to figure out. We don't know what they all do, but we know more or less what they all are. knowing what
我认为我们基本上知道一切。同样，会有一些我们不知道的细微差别，但我认为我们几乎知道一切。 >> 那很好。 >> 并不意味着我们知道所有这些东西的作用。这可能是下一代科学家需要弄清楚的生物化学前沿。我们不知道他们都做什么，但我们或多或少知道他们都是什么。知道什么
讲话人（自动字幕未标注）：
they are but not knowing what they do motivated us to go take these two proteins that were in the mitochondria. We could make a very strong hypothesis that they were important because they were in every cell that has mitochondria down to a yeast that's a single-sellled organism and plants and animals. Everything that has a mitochondria has these two NPC1 and NPC2 proteins. And it would probably uh take too long to
它们是，但不知道它们的作用是什么促使我们去获取线粒体中的这两种蛋白质。我们可以做出一个非常有力的假设，即它们很重要，因为它们存在于每个具有线粒体的细胞中，一直到酵母（单一销售的有机体）以及植物和动物中。所有有线粒体的东西都有这两种 NPC1 和 NPC2 蛋白。可能需要很长时间才能
讲话人（自动字幕未标注）：
explain on this podcast this the processes that we went through to try to identify the function of this MPC 1 and 2, but this was a a brilliant collaboration and I think one of the the highlights of my career. different people in my lab and in the lab of my colleague Carl Thumbl that worked together. Carl was a fly geneticist or is a fly geneticist that used his unique skills and and resources and we were using
在此播客中解释我们尝试识别 MPC 1 和 2 功能的过程，但这是一次出色的合作，我认为这是我职业生涯的亮点之一。我的实验室和我的同事 Carl Thumbl 的实验室里有不同的人一起工作。卡尔是一名苍蝇遗传学家，或者是一名利用他独特的技能和资源的苍蝇遗传学家，而我们正在使用
讲话人（自动字幕未标注）：
yeast as a model system as well as human cells and triangulating all that data. We came up with data that suggested that this might be the mitochondrial pyrovate carrier. these two unknown proteins that happened to be sitting in the mitochondria and that was now been validated many times over that these are the proteins that do this transport of pyrovate into the mitochondria. It was a really fun time for me as a
酵母作为模型系统以及人类细胞并对所有这些数据进行三角测量。我们得出的数据表明这可能是线粒体丙酮酸载体。这两种未知的蛋白质恰好位于线粒体中，现在已经被多次验证，这些蛋白质是将丙酮酸转运到线粒体中的蛋白质。这对我来说是一段非常有趣的时光
讲话人（自动字幕未标注）：
scientist to to see that happen. And you know, you kind of alluded to this when you asked the question, what was maybe even more exciting than the discovery of the mitochondrial pyrovate carrier, which Carl and I did, and we published a paper and the lab of JeanClaude Martin and Geneva published a paper at the same time showing the same discovery. What's been really fun since then is to see the implications of that
科学家来见证这一切的发生。你知道，当你问这个问题时，你有点暗示了这一点，什么可能比发现线粒体丙酮酸载体更令人兴奋，卡尔和我发现了这一点，我们发表了一篇论文，让克洛德·马丁和日内瓦的实验室同时发表了一篇论文，展示了同样的发现。从那时起，真正有趣的是看到它的含义
讲话人（自动字幕未标注）：
and starting again to understand what role this protein plays in the allocation of that pyrovate that we've been talking about because now the MPC is the first step towards one destination of that pyrovate. So it kind of pulls it into the mitochondria so to speak and once that pyrovate is in the mitochondria it's going to be used for something in the mitochondria instead of maybe being used for something else in the
并再次开始了解该蛋白质在我们一直在讨论的丙酮酸分配中发挥什么作用，因为现在 MPC 是迈向该丙酮酸目的地的第一步。因此，可以说，它会将其拉入线粒体，一旦丙酮酸进入线粒体，它将被用于线粒体中的某些东西，而不是可能被用于线粒体中的其他东西。
讲话人（自动字幕未标注）：
cytool. And so that's been work that that we've done a lot of since is what are the implications of that. And I think it's been exciting to see in different cell types what that means. And so cardiamyiotes for example again these are cells that want to make ATP to to allow cardiumes to continue to contract. They need to extract every bit of energy they can make as much ATP as they can. They use this MPC extensively.
细胞工具。因此，我们已经做了很多工作，这就是它的含义。我认为在不同的细胞类型中看到这意味着什么是令人兴奋的。以心肌细胞为例，这些细胞想要产生 ATP，以使心肌继续收缩。他们需要提取尽可能多的 ATP 能量。他们广泛使用这个 MPC。
讲话人（自动字幕未标注）：
How do they ensure that that these cardiammyioites make sure that they make just enough to maintain themselves so they they're not so busy burning up all the lumber that they end up going, "Oh my goodness," and the house fell apart. >> Yeah. >> Do they consistently devote 90% of of their ATP to energy utilization and that they just know 10%. Like how quantitative are these these these pathways? >> Because you can't
他们如何确保这些 cardiammyioites 确保他们赚到的钱足以维持自己的生活，这样他们就不会忙着烧掉所有的木材，以至于最终“哦，天哪”，房子就倒塌了。 >> 是的。 >> 他们是否始终将 90% 的 ATP 用于能量利用，而他们只知道 10%。这些途径的定量程度如何？ >> 因为你不能
讲话人（自动字幕未标注）：
you can't have the walls fall down. It doesn't matter how much energy you produce, right? It's a brilliant question and and it's definitely not programmed like like there's a a spigot with a diverter valve that 90% goes this way and 10% goes that way. What actually happens and this doesn't just happen in cardiammyioytes it happens in every cell is that basically the cell is measuring the outputs again to
你不能让墙倒塌。你产生多少能量并不重要，对吗？这是一个很棒的问题，而且它的编程绝对不像有一个带有分流阀的龙头，90% 朝这边走，10% 朝那边走。实际发生的情况不仅发生在心肌细胞中，而且发生在每个细胞中，基本上细胞正在再次测量输出以
01:10:00
讲话人（自动字幕未标注）：
anthropomorphize and I have to say there are some scientists that hate us when we anthropomorphize having an intelligence or an adaptive logic. So it's okay. >> I think you've provided cover for me to do it on for cells. Then >> cells basically are measuring their resources all the time. >> I think you could make a compelling argument that every cell almost all cells know how much usable energy ATP they have all the
拟人化，我不得不说，当我们拟人化拥有智力或适应性逻辑时，有些科学家会讨厌我们。所以没关系。 >> 我认为你已经为我提供了对细胞进行此操作的掩护。然后>>细胞基本上一直在测量它们的资源。 >> 我认为你可以提出一个令人信服的论点，即每个细胞几乎所有细胞都知道它们拥有多少可用能量 ATP
讲话人（自动字幕未标注）：
time. And when it gets low, they will initiate a series of reactions to that, responses to that to bring it back up. They'll turn off processes that use ATP. They'll start pulling glucose out of the circulation to make more ATP. There's this really profound response to ATP depletion. And I think that's true for many of the endroducts of our metabolic map. Again, these are the the the products of the metabolic map
时间。当它变低时，他们会对此发起一系列反应，以使其回升。他们将关闭使用 ATP 的进程。他们将开始将葡萄糖从循环中抽出，以产生更多的 ATP。 ATP 耗尽会产生非常深刻的反应。我认为对于我们代谢图谱中的许多内产物来说都是如此。同样，这些是代谢图的产物
讲话人（自动字幕未标注）：
are the amino acids that make proteins. And the nucleotides that are required to make DNA and RNA, our genome, >> there's a greediness to all these cells. If the fat cells are greedy, you could really see a problem like if we're not ingesting enough glucose. Let's let's hold off on ketosis for a second and alternate metabolic pathways. But we will touch on it. But if the fat cells are also very self- serving then
是制造蛋白质的氨基酸。制造 DNA 和 RNA、我们的基因组所需的核苷酸>>所有这些细胞都贪婪。如果脂肪细胞贪婪，你真的会看到一个问题，比如我们没有摄入足够的葡萄糖。让我们暂缓酮症的发展，选择第二种替代代谢途径。但我们会触及它。但如果脂肪细胞也非常自私的话
讲话人（自动字幕未标注）：
you know at some point are they just forced to liberate this stuff. But like ultimately fat cells just want to get bigger and bigger and that but if this cardomyite it doesn't have enough glucose eventually it's like it could shut down any number of things like you can remodel the house down to you know just the fireplace and a little bit of structure around it but eventually >> you need the resource. So then what
你知道在某些时候他们只是被迫解放这些东西。但就像最终脂肪细胞只是想变得越来越大，但如果这种豆蔻石最终没有足够的葡萄糖，它就像它可以关闭任何数量的东西，比如你可以把房子改造成你只知道壁炉和周围的一些结构，但最终>>你需要资源。那么然后呢
讲话人（自动字幕未标注）：
happens that atyposite liberates the energy. Yeah. >> And and cells everybody gets a little bit and you just hang on. So it's a famine type situation. >> Exactly. I mean just as insulin tells the body I just ate. >> We're good. Take that energy that's available in the form of glucose. Squirrel it away. Use it. There are hormones that do the opposite. Glucagon is one of them. And glucagon again has become a little
碰巧异质释放了能量。是的。 >> 每个人都会得到一点细胞，然后你就坚持下去。所以这是一种饥荒类型的情况。 >> 正是如此。我的意思是，就像胰岛素告诉身体我刚刚吃的东西一样。 >> 我们很好。获取以葡萄糖形式提供的能量。把它藏起来。使用它。有些激素的作用恰恰相反。胰高血糖素就是其中之一。胰高血糖素再次变得有点
讲话人（自动字幕未标注）：
bit more popular recently because it's now being combined in some of the GLP-1 uh more newer GLP-1 drugs. Glucagon is called a fasting hormone. So glucagon in many ways does the opposite of insulin. It will go to the fat cell, bind to the vat fat cell, tell the fat cell to take the fat that it has squirreled away and release it. And now that can go to other cells in the body, the heart. Heart is very good at
最近更受欢迎，因为它现在被结合在一些 GLP-1 呃更新的 GLP-1 药物中。胰高血糖素被称为空腹激素。因此，胰高血糖素在很多方面与胰岛素的作用相反。它会到达脂肪细胞，与脂肪细胞结合，告诉脂肪细胞带走它储存的脂肪并将其释放。现在它可以进入身体的其他细胞，即心脏。心很擅长
讲话人（自动字幕未标注）：
consuming fatty acids that come from atapost tissue. And so so that's good. >> I'm actually relieved to hear that. >> Yeah. >> Right. Because if if god forbid there's a shortage of food that lasts long enough, like that's definitely an organ I don't want shutting down. >> Exactly. And and most of us have fat in our fat cells. And and you could make an argument that the key destination of that fat is the heart to
消耗来自后组织的脂肪酸。所以这样很好。 >> 听到这个消息我真的很欣慰。 >> 是的。 >> 对。因为如果上帝不允许的话，食物短缺会持续足够长的时间，就像这绝对是一个我不想关闭的器官。 >> 正是如此。我们大多数人的脂肪细胞中都含有脂肪。你可以说脂肪的主要目的地是心脏
讲话人（自动字幕未标注）：
keep it alive. And you know in a normal human I think it's estimated 70 to 80% of the energy extraction that happens in cardiammyioytes and heart muscle cells is happening from fat. You said under fasted conditions is that >> especially under fasted conditions but even in fed conditions fat is is uh is available for the heart to use and and >> dietary fat or fat from adapocytes >> both whatever fat is in the
让它活下去。你知道，在正常人中，我认为心肌细胞和心肌细胞中提取的能量中，估计有 70% 到 80% 来自脂肪。你说在禁食条件下是>>特别是在禁食条件下，但即使在进食条件下脂肪也是可以供心脏使用的并且>>膳食脂肪或来自适应细胞的脂肪>>无论是在体内的任何脂肪
讲话人（自动字幕未标注）：
circulation the cardiammyioite is pretty good at taking it up and burning it making ATP from it >> yeah the brain likes glucose but it can use maybe now we I'm not super versed in in the ketogenic pathways but I know that our brain can thrive on ketones >> so carbohydrates are not quote unquote essential. You know, all the ketogenic folks love to say that there's no such thing as an essential carbohydrate. That
在循环中，cardiammyioite 非常擅长吸收它并燃烧它，从中产生 ATP>>是的，大脑喜欢葡萄糖，但它可以使用也许现在我们我不太精通生酮途径，但我知道我们的大脑可以在酮的帮助下茁壮成长>>所以碳水化合物并不是必不可少的。你知道，所有生酮人士都喜欢说不存在必需碳水化合物这样的东西。那
讲话人（自动字幕未标注）：
doesn't change the fact that like the preferred fuel source for most every cell is glucose. But anyway, that's a separate issue. >> You don't want the brain to shut down either. >> Yeah. >> So, if the form of energy changes, is it still once you get to mitochondria, pyuvate, MCP, and downstream, is it all the same? is essentially like energy is energy at that point or is or is there are there multiple pathways
并没有改变这样一个事实：大多数细胞的首选燃料来源是葡萄糖。但无论如何，这是一个单独的问题。 >> 你也不希望大脑停止运转。 >> 是的。 >> 那么，如果能量的形式发生了变化，那么一旦到达线粒体、丙酮酸、MCP 以及下游，是不是都一样呢？本质上就像能量是那个点的能量或者是或是否有多种途径
讲话人（自动字幕未标注）：
depending on the fuel source? >> Yeah, the ability of neurons to consume fatty acids is limited. I I think it's traditionally been thought that it's very close to zero. I think that's being questioned now, but it's limited. As you allude to neurons are particularly fond of consuming glucose and use that glucose to make their ATP. And you know that obviously puts a very stringent demand on the body to always have
取决于燃料来源？ >> 是的，神经元消耗脂肪酸的能力是有限的。我认为传统上人们认为它非常接近于零。我认为现在有人对此提出质疑，但这是有限的。正如您提到的，神经元特别喜欢消耗葡萄糖并利用葡萄糖来制造 ATP。你知道这显然对身体提出了非常严格的要求
讲话人（自动字幕未标注）：
glucose available. Glucose is one of these things that's fascinating the the systems that we have in our body to maintain glucose. You know diabetes is defined as high blood sugar. That is the definition the clinical definition of diabetes when basically our body does not adequately limit the circulating glucose and that is destructive damaging but it's damaging on the in the course of years right a person can live
可用葡萄糖。葡萄糖是让我们体内维持葡萄糖的系统着迷的物质之一。您知道糖尿病被定义为高血糖。这就是糖尿病的临床定义，基本上我们的身体不能充分限制循环葡萄糖，这是破坏性的，但它会损害一个人可以生存的岁月。
讲话人（自动字幕未标注）：
with diabetes for years before succumbing to it if glucose is too low you die within minutes if not seconds and that I think for a few different reasons but probably the most important one is the brain requires some amount of uh glucose to keep it functioning. So you know again I I alluded to this before this very elaborate dance that is happening by these individual cells taking up different nutrients out of the
在屈服于糖尿病之前，如果血糖太低，你会在几分钟甚至几秒内死亡，我认为有几个不同的原因，但可能最重要的一个是大脑需要一定量的葡萄糖来保持其功能。所以你又知道了，我在这个非常复杂的舞蹈之前提到过这一点，这些舞蹈是由这些单独的细胞从细胞中吸收不同的营养物质而发生的。
讲话人（自动字幕未标注）：
circulation using them for their own unique purposes and and neurons again are are very adept at taking in glucose and burning it and making ATP from it. I think again the heart I I feel like is really fascinating because it'll it'll eat anything. It's an omnivore. Fats, glucose, lactate, ketones, amino acids. It will make ATP out of just about anything that ATP can be made out of. And again, that's important for us
循环系统将它们用于其独特的目的，并且神经元再次非常擅长吸收葡萄糖并燃烧它并从中产生 ATP。我再次觉得我的心真的很迷人，因为它会吃任何东西。它是杂食动物。脂肪、葡萄糖、乳酸盐、酮、氨基酸。它将用任何可以制造 ATP 的东西来制造 ATP。再说一遍，这对我们很重要
讲话人（自动字幕未标注）：
to enable us to live no matter whether we just ate or not. Heart is very good at that. So I think this elaborate dance that we have going on in our body all the time between different cells cells doing it different way taking in different fuels and uh using them for their unique purposes. >> What is the consequence of eliminating the M MCP a shuttle like you get like if you take a mouse you're at the University of
使我们无论是否吃饭都能够生存。心在这方面非常擅长。所以我认为我们体内不同细胞之间一直在进行这种精心设计的舞蹈，细胞以不同的方式吸收不同的燃料，并将它们用于其独特的目的。 >> 消除 M MCP 的后果是什么，就像你在大学里拿一只鼠标一样
讲话人（自动字幕未标注）：
Utah let's give a shout out to Mario Kapi whose life story is amazing who won a Nobel Prize for essentially developing what are called knockout mice among other things. um you can eliminate genes to test the role of a particular protein downstream of that gene. If you make a mouse that lacks these proteins, do you get a dead mouse? So >> they do not survive to birth. Yeah, >> you can get sperm egg and a and that
犹他州让我们向马里奥·卡皮致敬，他的人生故事令人惊叹，他因开发出所谓的基因敲除小鼠等技术而获得了诺贝尔奖。嗯，你可以消除基因来测试该基因下游特定蛋白质的作用。如果你培育出一只缺乏这些蛋白质的老鼠，你会得到一只死老鼠吗？所以>>他们无法存活到出生。是的，>>你可以获得精卵和那个
讲话人（自动字幕未标注）：
somehow the >> it can become a a mouse. >> Yeah, it'll start to develop and then I think if I remember right, it's about 12 or 13 days of development, which is >> you know 2/ird of the way from fertilization [clears throat] to birth of the mouse, it will die and and you won't get a live mouse. But what has been done and and obviously you were probably getting there is because of the technologies that Mario developed
不知何故>>它可以变成一只老鼠。 >> 是的，它会开始发育，然后我想，如果我没记错的话，大约需要 12 或 13 天的发育时间，也就是 >> 你知道，从受精（清喉咙）到老鼠出生的过程中，它会死亡，而你不会得到一只活老鼠。但已经完成的事情，显然你可能已经做到了，因为马里奥开发的技术
讲话人（自动字幕未标注）：
and then others following after him, we can now make mice that lack the MPC only in the liver or only in the heart or only in the muscle or only in the brain and many of these things have been done. >> Sorry, I should have been given credit. He developed a technology that would allow for organ and cell type specific deletions or additions of genes. forgive me but you reminded me like in all much to so >> yeah and
然后其他人追随他，我们现在可以制造仅在肝脏、仅在心脏、仅在肌肉或仅在大脑中缺乏 MPC 的小鼠，并且其中许多事情已经完成。 >> 抱歉，我应该得到认可。他开发了一种技术，可以对器官和细胞类型进行特定的基因删除或添加。原谅我，但你提醒了我很多事情>>是的，
讲话人（自动字幕未标注）：
many people have been contributing that technology and different ways to use it for decades now and as you might imagine given the unique demands of different cells the effects are different the heart is again very focused its metabolic program is focused on generating ATP so what if we eliminate the MPC in the heart so we have now made ATP P generation from glucose less efficient. We've we've now cut off the
几十年来，许多人一直在贡献这项技术和不同的使用方式，正如你可能想象的那样，考虑到不同细胞的独特需求，效果是不同的，心脏再次非常专注，其代谢程序专注于生成 ATP，那么如果我们消除心脏中的 MPC，那么我们现在可以降低从葡萄糖生成 ATP P 的效率。我们现在已经切断了
讲话人（自动字幕未标注）：
ability to use mitochondria at least in the conventional way. So I actually think the results of that experiment are fascinating and this is work that has been done by a few different labs. Akmed Clinton who's a postoc now running his own lab at Rutgers was the one who started this and uh other people have contributed. What essentially happens to that heart is that it lives and the animal lives for weeks after that.
至少以传统方式使用线粒体的能力。所以我实际上认为该实验的结果很有趣，这是由几个不同的实验室完成的工作。阿克迈德·克林顿 (Akmed Clinton) 是一名博士后，现在在罗格斯大学经营自己的实验室，他是发起这项工作的人，呃，其他人也做出了贡献。本质上发生在心脏上的事情是它活了，而动物在那之后还活了几周。
讲话人（自动字幕未标注）：
But eventually the animals die. And when you look at what they die of, they have a massive heart. They die of heart failure. And what has become clear as we've gone and done more sophisticated analyses of this heart and why they die. It's pretty clear that they don't die from an inability to make ATP because they can burn other things to make ATP. We talked about this. They can burn fats. They burn fats just fine.
但最终动物们都会死去。当你看到他们死于什么时，你会发现他们有一颗巨大的心。他们死于心力衰竭。当我们对这颗心脏进行更复杂的分析以及它们死亡的原因时，一切都变得清晰起来。很明显，它们不会因无法生成 ATP 而死亡，因为它们可以燃烧其他物质来生成 ATP。我们讨论过这个。它们可以燃烧脂肪。它们燃烧脂肪效果很好。
讲话人（自动字幕未标注）：
What they appear to die from, and I would say I'm speculating a bit here, we don't have all the answers to all the questions, is they have made a resource allocation decision that turns out to be pathological for them. And instead of using the glucose that they take in to burn it and make ATP, they start making biomass. That that again we talked about that that bifurcation. We've eliminated their ability to make ATP
他们似乎死于什么，我想说我在这里推测了一下，我们没有所有问题的全部答案，是他们做出了一个资源分配决定，结果对他们来说是病态的。他们不再使用摄入的葡萄糖来燃烧并制造 ATP，而是开始制造生物质。我们再次谈到了那个分歧。我们已经消除了他们制造 ATP 的能力
讲话人（自动字幕未标注）：
from it at least as effectively and instead they make biomass. They grow. And when cardiamyioytes grow that creates structural problems for the heart. Almost every human that succumbs to heart failure will end up with a big dilated heart that's less effective at pumping. And that's what we see in in the mouse really. And that maybe tells us something about the fundamental importance of this resource allocation
至少同样有效地从中提取生物质。他们成长。当心肌细胞生长时，就会给心脏带来结构性问题。几乎每个死于心力衰竭的人最终都会出现心脏扩张、泵血效率降低的情况。这就是我们在鼠标中真正看到的。这也许告诉我们这种资源分配的根本重要性
讲话人（自动字幕未标注）：
decision. And this is obviously just in the context of cardiammyioytes. But again, that resource allocation decision is happening in every cell in our body all the time. And that's one reason why I'm fascinated with this field is we're just starting to understand how those resource allocation decisions are made. What are the implications of making them correctly and incorrectly? And maybe even more excitingly, can
决定。这显然只是在心肌细胞的背景下。但同样，资源分配决策一直发生在我们身体的每个细胞中。这就是我对这个领域着迷的原因之一，因为我们才刚刚开始了解这些资源分配决策是如何做出的。正确和错误地制作它们会产生什么影响？也许更令人兴奋的是，可以
01:20:00
讲话人（自动字幕未标注）：
we go and fix that? When a cardiamyioite or when a heart more aptly is making a resource allocation decision that is pathological, can we fix it? Can we find a a therapeutic that will go and correct that and rewire it in the appropriate and healthy way and can that then restore the proper function of the heart? Again, I think we're at the at the frontier of this field, but it's a really exciting place that that our
我们去解决这个问题吗？当心肌细胞或更恰当地说是心脏做出病态的资源分配决策时，我们可以修复它吗？我们能否找到一种治疗方法来纠正这一点，并以适当和健康的方式重新连接它，然后才能恢复心脏的正常功能？再说一次，我认为我们处于这个领域的前沿，但这是一个非常令人兴奋的地方，我们的
讲话人（自动字幕未标注）：
field exists now where we're starting to understand the problems and we're starting, I would say, early in developing the right agents to act and to manipulate this metabolic map that might be able to fix things. I'd like to take a quick break and acknowledge our sponsor, Function. Function provides over 160 advanced lab tests to give you a clear snapshot of your bodily health. This snapshot gives you insights into
现在存在一个领域，我们开始了解这些问题，我想说，我们很早就开始开发合适的药物来采取行动并操纵这个可能能够解决问题的代谢图。我想稍微休息一下并感谢我们的赞助商 Function。功能提供超过 160 项高级实验室测试，让您清晰了解自己的身体健康状况。这张快照让您深入了解
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your heart health, your hormone health, autoimmune function, nutrient levels, and much more. They've also recently added access to advanced MRI and CT scans. Function not only provides testing of over 160 biomarkers key to your physical and mental health, it also analyzes these results and provides recommendations for improving your health from top doctors. For example, in a recent test with function, I learned that
您的心脏健康、激素健康、自身免疫功能、营养水平等等。他们最近还增加了先进的 MRI 和 CT 扫描的访问权限。 Function 不仅提供对您身心健康至关重要的 160 多种生物标记物的测试，还分析这些结果并提供顶级医生改善您健康的建议。例如，在最近的一次功能测试中，我了解到
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some of my blood lipids were slightly out of range. As a result, I decided to start supplementing with nattokinise, which can naturally help reduce LDL cholesterol, and it did. In a follow-up test, I could confirm that this strategy worked. My blood lipids are now back exactly where I want them. Comprehensive lab testing of the sort that function offers is just so important for health. I mean, how else are you going
我的一些血脂稍微超出了范围。因此，我决定开始补充纳豆激酶，它自然可以帮助降低低密度脂蛋白胆固醇，而且确实如此。在后续测试中，我可以确认这个策略是有效的。我的血脂现在完全回到了我想要的水平。功能提供的全面实验室测试对于健康非常重要。我的意思是，你还要怎么走？
讲话人（自动字幕未标注）：
to know what's going on under the hood? And while I've been doing blood work for years, it used to be timeconuming, complicated, and expensive. In fact, I used to spend thousands of dollars per year trying to get this kind of data. And the data, frankly, were not all that good. But now with Function, it's extremely easy and affordable. A Function membership is only a dollar a day, $365 a year. And if you think about
知道幕后发生了什么？虽然我从事血液检查已有多年，但它曾经非常耗时、复杂且昂贵。事实上，我过去每年花费数千美元试图获取此类数据。坦率地说，数据并不那么好。但现在有了 Function，它变得非常简单且经济实惠。 Function 会员每天仅需 1 美元，每年 365 美元。如果你想
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the information it provides and the health challenges it helps you avoid and the proactive things that it can do for you to enhance your health, I truly look at it as a savings. To learn more, visit functionhealth.com/huberman and use the code hubberman for a $50 credit towards your membership. Again, that's functionhealth.com/huberman. So, is it fair to say that the allocation of energy, which is made pathologic in
它提供的信息、它帮助您避免的健康挑战以及它可以为您做的积极的事情来增强您的健康，我确实将其视为一种节省。要了解更多信息，请访问 functionhealth.com/huberman 并使用代码 hubberman 获得 50 美元的会员积分。同样，这是 functionhealth.com/huberman。那么，可以公平地说，能源的分配是病态的吗？
讲话人（自动字幕未标注）：
this mutant mouse, but also in people who have these uh cardiac conditions and die of heart attack essentially. It's almost like the the identity of the cells is screwed up. They're still a cardommyioite, >> but they're devoting too much energy to making more of themselves and not enough to to doing what they're supposed to do. I have like two analogies that I want to throw out there and maybe they they're too much
这种突变小鼠，也存在于患有这些呃心脏病并基本上死于心脏病发作的人身上。这几乎就像细胞的身份被搞砸了一样。他们仍然是一个小豆豆，>>但他们投入了太多的精力来让自己变得更好，而没有足够的精力去做他们应该做的事情。我想抛出两个类比，也许它们太多了
讲话人（自动字幕未标注）：
of a reach, but I love dogs. I have a now a medium-sized dog. I used to have a large dog. The larger breeds of dogs live much shorter lives than the smaller ones. And and we actually know >> that's because of dosing of IGF-1, which is a growth pathway thing. So there is this like story about larger animals within a given species tend to live much shorter lives than the smaller variety of that same species. There's
达不到，但我喜欢狗。我现在有一只中型狗。我曾经养过一只大狗。较大品种的狗的寿命比较小品种的狗短得多。我们实际上知道 >> 这是因为 IGF-1 的剂量，这是一种生长途径。因此，有一个类似的故事，关于特定物种中的大型动物往往比同一物种中较小的物种寿命短得多。有
讲话人（自动字幕未标注）：
some exceptions to this, but there does seem to be a sort of rule that like you can either be big and live a short life or you can be small and live a longer life within certain species. >> But there's also this thing about heartbeats, right? Like this theory that you only get so many heartbeats in your life. The reason I I like these higher level perhaps appropriate comparisons, a lot of caveats there, is that like
也有一些例外，但似乎确实有一种规则，在某些物种中，你要么体型大，寿命短，要么体型小，寿命更长。 >> 但还有关于心跳的事情，对吧？就像这个理论一样，你一生中只能得到这么多的心跳。我喜欢这些更高层次的也许适当的比较的原因，其中有很多警告，就像
讲话人（自动字幕未标注）：
ultimately when I think about life and evolution and a propagation of species and health versus pathology, it's all about energy, right? It's like how are you devoting energy? It can get into the kind of mystical spiritual piece. That's not our purpose. There's not my purpose in in bringing this up now, but >> it seems like at the cellular level and at the subcellular level, which is what you're describing, >> the
最终，当我思考生命、进化、物种传播、健康与病理时，一切都与能量有关，对吗？就像你如何投入精力？可以进入那种神秘的精神片。那不是我们的目的。我现在提出这个问题并不是我的目的，但是 >> 似乎在细胞水平和亚细胞水平上，这就是你所描述的，>>
讲话人（自动字幕未标注）：
allocation of energy in this case is the difference between life and death, but but this this decision, you're not telling us like, oh, you know, these pathways I discovered along with others are really like there's a a fan out of like 50 different options. You're saying make more >> biomass, more of self, [snorts] or use energy to be self. Mh. >> And there seems to be like a critical balance there. And I have
在这种情况下，能量的分配是生与死的区别，但是这个决定，你不会告诉我们，哦，你知道，我和其他人一起发现的这些途径真的就像有一个粉丝从大约 50 种不同的选择中选出。你是说制造更多>>生物质，更多的自我，[哼哼]或者使用能量来成为自我。姆赫。 >> 那里似乎存在一种关键的平衡。我有
讲话人（自动字幕未标注）：
another story I could tell about how like if you look at the data on longevity in different athletes like the gymnasts, the sprinters seem to live 3 to six years longer on average than than others. And the endurance runners are somewhere in the middle. You look at very large athletes like the powerlters and the um moving aside all things of like use of drugs in sports, you go like >> the the sports where there's
我可以讲另一个故事，如果你看看体操运动员等不同运动员的寿命数据，短跑运动员似乎比其他运动员平均寿命长 3 到 6 年。耐力跑运动员则处于中间位置。你看看像强力运动员这样的大运动员，嗯，把所有像在运动中使用药物这样的事情放在一边，你就会像 >> 那些有的运动
讲话人（自动字幕未标注）：
just a lot more of somebody that's not good for longevity and it really isn't. So there does seem to be this balance between size and the use of fuel to to build more of oneself and the use of fuel to just be oneself. And that self could be a cell. >> Yeah. >> That self could be an organ. >> That self could be a whole organism. And I find that like not incidental, but maybe I'm taking too many liberties here. >>
只是更多的人不利于长寿，事实并非如此。因此，在规模和使用燃料来构建更多自己以及使用燃料来成为自己之间似乎确实存在这种平衡。这个自我可能是一个细胞。 >> 是的。 >>那个自我可能是一个器官。 >>那个自我可能是一个完整的有机体。我发现这并不是偶然的，但也许我在这里太随意了。 >>
讲话人（自动字幕未标注）：
Yeah. I mean that's a that's a complex analogy. and and but I think one thing that is very clear about about what you're talking about is this sense of of of identity in a cell. I that's a fundamentally important phenomenon that again we've known about for a long time and there's been under an understanding in some cell types in some ways about how that identity is established and maintained. But I think your
是的。我的意思是这是一个复杂的类比。但我认为你所谈论的非常清楚的一件事是细胞中的这种身份感。这是一个非常重要的现象，我们已经知道很长时间了，并且在某些细胞类型中以某种方式了解了这种身份是如何建立和维持的。但我认为你的
讲话人（自动字幕未标注）：
question is a really interesting one. To what extent is disease associated with loss of that cell identity? And and cell identity is a bit of a squishy parameter. You know, how do you measure what a cell thinks it is? You know, there's no function, right? So, yeah, like when we had Max Crumbl on the podcast, he was like, you know, every one of your cells by the time you reach our age, roughly, you know, in our 30s,
问题是一个非常有趣的问题。疾病在多大程度上与细胞身份的丧失相关？而且小区身份是一个有点模糊的参数。你知道，如何测量细胞的想法？你知道，没有任何功能，对吧？所以，是的，就像我们在播客中邀请 Max Crumbl 时一样，当你达到我们这个年龄时，你知道，他就像你的每一个细胞，大约，你知道，在我们 30 多岁的时候，
讲话人（自动字幕未标注）：
no, I'm kidding. in our 50s, early 50s, is we're a mosaic of like our original genetic makeup plus all these mutations that have accumulated. Nobody likes that picture. That's true. We're a patchwork of like our former self and our newer self. >> That's one form of cell identity. What I like here is that you're talking about within an organ, within a cell type, >> you sort of have a choice of a make more of oneself
不，我在开玩笑。在我们 50 多岁、50 岁出头的时候，我们是由我们最初的基因构成加上所有这些积累的突变组成的马赛克。没有人喜欢那张照片。这是真的。我们是过去的自己和新的自己的拼凑而成。 >> 这是细胞身份的一种形式。我在这里喜欢的是你在一个器官内，在一个细胞类型内谈论，>>你可以选择让自己变得更好
讲话人（自动字幕未标注）：
or b just be you. >> Yeah. So there's something like kind of like to me conceptually sticky about this notion of size versus use. >> Yeah. I think I as you say I I think that in a way we're talking again about resource allocation allocating to energy versus making more stuff that could mean another cell or a bigger cell. >> There's many examples of where making more stuff instead of making more energy is
或者 b 就是你。 >> 是的。因此，对我来说，尺寸与用途的概念在概念上有些粘性。 >> 是的。我想，正如你所说，我认为，在某种程度上，我们正在再次讨论分配给能源的资源分配，而不是制造更多的东西，这可能意味着另一个细胞或更大的细胞。 >> 有很多例子表明，制造更多的东西而不是制造更多的能源
讲话人（自动字幕未标注）：
pathological. We talked about cancer. We talked about the heart getting pathologically bigger. Immune cells becoming hyperactivated can lead to inflammatory diseases. You know, there's many examples of that. >> So, I think this is all playing out at the level of individual cells and what you're talking about is obviously a bigger uh conceptual framework in which to think about it. But I think there is that uh
病态的。我们谈论了癌症。我们谈到心脏病理性变大。免疫细胞过度活跃会导致炎症性疾病。你知道，这样的例子有很多。 >> 所以，我认为这一切都是在单个细胞的层面上发生的，你所谈论的显然是一个更大的呃概念框架来思考它。但我认为有那个呃
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connection and I don't know this is a bit non-scientific but I I do think it's fascinating to understand the historical philosophical ways that our ancestors thought about the world >> and we [snorts] find relics of that in our science right that we can see reflected in the discoveries that are made today. I don't want to take us off the biology, but if we can go down this pathway a little bit more, you know, I
我不知道这有点不科学，但我确实认为理解我们祖先思考世界的历史哲学方式是很有趣的>>并且我们[哼哼]在我们的科学权利中找到了这种遗迹，我们可以在今天的发现中看到它们的反映。我不想让我们脱离生物学，但如果我们能沿着这条路多走一点，你知道，我
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sometimes think about energy in terms of human interactions and and I think most of us can think of the extremes of benevolent versus malevolent energy exchange like like let's say somebody like money is just >> a tool, right? Like people say money is energy. That sounds very like, you know, like internety, but really it it can be exchanged for something, right? We've decided that. And if somebody steals from us or
有时从人类互动的角度来思考能量，我认为我们大多数人都可以想到善意与恶意能量交换的极端，就像我们说像金钱这样的人只是>>一种工具，对吗？就像人们说的，金钱就是能量。这听起来很像互联网，但实际上它可以用来交换某些东西，对吧？我们已经决定了。如果有人偷了我们的东西或者
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they they promise something and it turns out they overcharge us or something like that like we fundamentally understand the math there. You said it was going to cost us this much cost. You said it was going to be this and instead I got that and this isn't what I paid for. Right? But if you look at human interaction and behavior, the stuff that we consider malevolent is usually when something when someone perceives
他们承诺了一些事情，结果证明他们向我们收取了过高的费用或类似的事情，就像我们从根本上理解那里的数学一样。你说我们要花这么多钱。你说会是这个，但我却得到了那个，这不是我付钱买的。正确的？但如果你看看人类的互动和行为，我们认为恶意的东西通常是当某人察觉到某事时
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the energy has been stolen from them. Usually in the form of time, >> but often in the form of physical energy because time is physical energy, right? >> And then benevolent acts are generally ones in which there's a either an even or a kind of a um like a >> net positive exchange of energy. And this is like a lot of what structures human interactions. Like I don't want to take us too far. This is not a psychology
他们的能量被偷走了。通常以时间的形式，>>但通常以物理能量的形式，因为时间就是物理能量，对吗？ >> 然后，仁慈的行为通常是存在一种偶数或某种嗯，如 >> 净正能量交换。这就像构建人类互动的许多因素一样。好像我不想带我们走得太远。这不是心理学
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podcast, but think about this all the time and like why I like zooming down at the level of the cell is we can find there there isn't going to be a perfect relationship between the cell and human interactions at large. But this notion of no cell if it wants what best for itself and therefore the organ it resides in and therefore the organism. >> Yeah. >> Can afford to really cheat itself. >> That's right. like bring
播客，但一直想一想这一点，就像为什么我喜欢在细胞水平上缩小一样，我们可以发现细胞和人类相互作用之间不会存在完美的关系。但是，如果细胞想要为自己以及它所居住的器官以及有机体提供最好的东西，那么就没有细胞的概念。 >> 是的。 >> 真的可以欺骗自己。 >> 没错。喜欢带
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it down to like the individual cell. You can't like the cell can't afford to cheat itself, >> right? >> And if too many cells do that, you end up with a big heart that doesn't pump. >> Exactly. >> So, it cheated itself. >> Yeah. >> For me, that's very useful. I don't know if it is for anyone else. So, when I think about like really critical biology, all these proteins, like which ones are you going to study? Like,
细化到喜欢单个细胞。你不可能认为细胞无法欺骗自己，>>对吗？ >> 如果太多的细胞这样做，你最终会得到一个不跳动的大心脏。 >> 正是如此。 >> 所以，它欺骗了自己。 >> 是的。 >> 对我来说，这非常有用。我不知道是否适合其他人。所以，当我想到真正关键的生物学时，所有这些蛋白质，比如你要研究哪些？喜欢，
01:30:00
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it's clear to me now why this set of proteins is very important. Yeah. >> Very, very important. What I didn't get was how you actually found it. So was it that you knew there was a gene there that coded for this thing of a certain size? So you started making some what we call recominant version of that and like throwing it on cells seeing what happened. Is that kind of the the steps that went through? >> We knew the
我现在很清楚为什么这组蛋白质非常重要。是的。 >> 非常非常重要。我不明白的是你实际上是如何找到它的。那么你是否知道那里有一个基因编码了这个具有一定大小的东西？所以你开始制作一些我们所说的重组版本，并将其扔到细胞上看看会发生什么。这就是所经历的步骤吗？ >> 我们知道
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protein was there. What we didn't know is what it did. >> Mhm. >> And I would say the key discoveries of that came from genetics. Basically Carl's lab made flies that lacked the MPC and we could then >> they were actually alive. There's an interesting story there that's probably too in the weeds, but they live, [snorts] >> but they had specific manifestations that we could analyze using >> chemistry. [snorts] And
蛋白质就在那里。我们不知道的是它做了什么。 >> 嗯。 >> 我想说，其中的关键发现来自遗传学。基本上，卡尔的实验室制造了缺乏 MPC 的苍蝇，然后我们可以>>它们实际上是活的。那里有一个有趣的故事，可能也在杂草中，但它们活着，[哼哼]>>但它们有我们可以使用>>化学分析的特定表现。 [哼哼]还有
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I'll tell you about the results of that. We were studying it in other in other cell types in yeast cells and in human cells and studying the results of losing these genes. You know, again, this is what's enabled by doing genetics. You know, Mario Capeki figured out how to do this in mice and his colleagues that gave us the ability to do knockout mice. Other people have enabled it in other species. And by doing that
我会告诉你结果。我们正在酵母细胞和人类细胞的其他细胞类型中研究它，并研究失去这些基因的结果。你知道，这也是通过遗传学实现的。你知道，马里奥·卡佩基（Mario Capeki）想出了如何在老鼠身上做到这一点，他的同事让我们有能力敲除老鼠。其他人已经在其他物种中启用了它。通过这样做
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and studying the results, we could then deduce, oh, what's happening in these yeast cells, these fruit flies, and these human cells grown on a dish is they aren't able to take their pyrovate into the mitochondria. You know by analyzing them using sophisticated chemical tools we could see that they were basically their metabolic pathway from glucose to pyrovate to pyrovate in the mitochondria to ATP that was being
通过研究结果，我们可以推断出，哦，这些酵母细胞、这些果蝇和这些在培养皿中生长的人类细胞中发生了什么，它们无法将丙酮酸带入线粒体。你知道，通过使用复杂的化学工具分析它们，我们可以看到它们基本上是从葡萄糖到丙酮酸，再到线粒体中的丙酮酸到 ATP 的代谢途径。
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blocked and it was being blocked specifically at that level of the pyrovate. So that then gave us the initial hypothesis maybe that's what these proteins are doing and we could then go and validate that hypothesis in multiple experiments and that like I said been validated by many other people over the ensuing decade or so. So those were the experiments that enabled us to to figure it out. It was really um genetics
被阻断，并且它在丙酮酸盐的水平上被特别阻断。因此，这给了我们最初的假设，也许这就是这些蛋白质正在做的事情，然后我们可以在多个实验中验证这个假设，就像我说的，在接下来的十年左右的时间里，这个假设得到了许多其他人的验证。这些实验使我们能够弄清楚这一点。这真的是嗯遗传学
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that enabled us to do it. >> Very satisfying when a discovery comes about in yeast flies and mamalon including human cells. What year span was all of that happening if you had to really tighten it? >> Yeah, we published the paper in 2012. It probably was going on from 2008 or 9 to 2012, something something like that. >> This is actually an important moment, I think, for people to understand like when they hear about
这使我们能够做到这一点。 >> 当在酵母蝇和 mamalon（包括人类细胞）中发现新发现时，我感到非常满意。如果你必须真正收紧的话，这一切发生在哪一年？ >> 是的，我们在 2012 年发表了这篇论文。它可能是从 2008 年或 9 月到 2012 年发生的，类似的事情。 >> 我认为，这实际上是一个重要的时刻，让人们能够理解，就像当他们听到
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yeast or flies. They're probably like like why why are we doing this stuff? And I'm not here to like plug federal funding for research. I think that just happens naturally as a consequence of the podcast. Or at least I hope so. But my graduate adviser told me that yeast like they have a very quick turnover. So that's why they're good to use. And and she said that um she was a wine drinker. She said and they were
酵母或苍蝇。他们可能会问我们为什么要做这些事情？我来这里并不是为了支持联邦研究经费。我认为这是播客的自然结果。或者至少我希望如此。但我的研究生导师告诉我，酵母的周转速度非常快。这就是为什么它们很好用。她说，嗯，她是个喝酒的人。她说，他们是
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much smarter than us because they know how to make their own alcohol. [laughter] So now we know why biologists use yeast. >> Fruit flies. It's because of the short generation time. You can get a lot of experiments >> done. And they they have many of the the same structures that a human does. You know, not exactly obviously, but they have many structures that human does. And there's some things that they're
比我们聪明得多，因为他们知道如何自己酿造酒精。 [笑声] 现在我们知道为什么生物学家使用酵母了。 >> 果蝇。这是因为生成时间短。您可以完成很多实验>>。它们有许多与人类相同的结构。你知道，不完全明显，但它们有许多人类的结构。有些东西是
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particularly good at. You can look at the whole thing in the microscope and see different cells and different features. And I would say again, not to plug our specific experiments, but we could not have made that discovery with any one type of organism. If we just had the yeast data, we wouldn't have figured it out. If we just had the flight data, we wouldn't have figured it out. >> Same with the the human cell
特别擅长。你可以在显微镜下观察整个物体，看到不同的细胞和不同的特征。我要再说一遍，不要阻止我们的具体实验，但我们不可能用任何一种类型的生物体做出这一发现。如果我们只有酵母数据，我们就无法弄清楚。如果我们只有飞行数据，我们就无法弄清楚。 >> 与人体细胞相同
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data. But putting it all together, we could triangulate what we were seeing in one to what we were seeing in the other, and it became obvious that this is the hypothesis we should pursue. And I I think that's been obviously an effective strategy that's been employed by scientists for a long time is to take multiple different approaches, multiple different model systems to answer a complicated question. >> Let's talk
数据。但把它们放在一起，我们可以将我们在一个中看到的内容与我们在另一个中看到的内容进行三角测量，很明显，这是我们应该追求的假设。我认为这显然是科学家长期以来采用的一种有效策略，即采用多种不同的方法、多种不同的模型系统来回答一个复杂的问题。 >> 我们来谈谈
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about lactate. >> Every time lactate's come up on this podcast before, it's been the in the context of exercise physiology. We had the the great Andy Galpin, whose name I don't expect you to recognize, but he's he's really one of the like pre-minent public educator. He's a professor of physiology and exercise physiology. And he told us and he told the world like everyone talks about lactic acid. We don't actually
关于乳酸。 >> 以前每次在这个播客中提到乳酸时，都是在运动生理学的背景下出现的。我们有伟大的安迪·加尔平（Andy Galpin），我不希望你认出他的名字，但他确实是一位杰出的公共教育家。他是生理学和运动生理学教授。他告诉我们，他告诉世界，就像每个人都谈论乳酸一样。我们实际上并不
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make lactic acid. We make this thing called lactate. But within the cell lactate plays a very crucial role in this metabolic pathway. I know you spent some time with lactate. So when you think about lactate what do you think about? >> I mean so pyrovate we talked about pyrovate extensively >> to a first approximation. Again it's a little more complicated than this but I think this is a good way to think about it.
制造乳酸。我们生产这种叫做乳酸的东西。但在细胞内，乳酸在这一代谢途径中起着非常关键的作用。我知道你花了一些时间接触乳酸。那么，当您想到乳酸时，您会想到什么？ >> 我的意思是，我们广泛讨论了丙酮酸>> 到了第一个近似值。这又比这更复杂一些，但我认为这是一个很好的思考方式。
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When pyrovate is made simplistically has two fates. It can go into the mitochondria we talked about. What we didn't talk about is the other major fate is to be converted to lactate and exported. And that decision burn it make lactate. I think you could make a very strong argument is one of the most important metabolic decisions that cells are making all the time. >> Why would it not burn it or make more of itself
当丙酮酸被简单地制造出来时，有两种命运。它可以进入我们谈到的线粒体。我们没有谈论的是另一个主要命运是转化为乳酸并出口。这个决定会燃烧它产生乳酸。我认为你可以提出一个非常有力的论点，这是细胞一直在做出的最重要的代谢决定之一。 >> 为什么它不把它烧掉或者自己制造更多
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because it's just got it in excess? >> Yeah. There's something about that production of lactate that enables ongoing production of biomass. So again, a little more complicated than this. If you burn the pyrovate, that turns into carbon dioxide. We breathe it out. That the stuff is gone. We breathe it out. There's no stuff. There's just the energy. If you don't burn it, that stuff doesn't get eliminated as carbon
因为它只是过量了？ >> 是的。乳酸的生产能够持续生产生物质。再说一次，比这更复杂一点。如果燃烧丙酮酸，就会变成二氧化碳。我们把它呼出来。那东西不见了。我们把它呼出来。没有东西了这里只有能量。如果你不燃烧它，这些东西就不会以碳的形式被消除
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dioxide and can turn into a protein. can contribute to protein production or carbohydrate production or you know fatty acids that can be used to make make new cells. And so that really is the that resource allocation decision as we talked about many times building or burning. And lactate is one of the mediators in a way of that building decision. And so lactate I think historically has been thought of as a waste
二氧化碳，可以转化为蛋白质。可以有助于蛋白质的产生或碳水化合物的产生，或者您知道可以用来制造新细胞的脂肪酸。这确实是我们多次讨论的建设或销毁的资源分配决策。在某种程度上，乳酸是这种构建决策的调节因素之一。所以我认为乳酸在历史上一直被认为是一种浪费
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product when our cells can't burn typically because of lack of oxygen. We haven't talked so much about the role of oxygen and all this. When I talk about burning, what I really mean is taking that pyrovate or fatty acids or other things and oxidizing them using oxygen and ex by so doing extracting the energy and doing this unbelievably amazing chemistry that the mitochondria do to basically very effectively capture
当我们的细胞通常由于缺氧而无法燃烧时，就需要使用产品。我们还没有过多讨论氧气的作用以及所有这些。当我谈论燃烧时，我真正的意思是获取丙酮酸盐或脂肪酸或其他物质，并使用氧气和前体将它们氧化，通过提取能量并进行线粒体基本上非常有效地捕获的令人难以置信的惊人化学反应
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all that energy and make it usable in the form of ATP. When oxygen isn't available, that pyrovate cannot be burned and then it essentially has to be converted to lactate. That's why when we exercise and our muscle becomes hypoxic or doesn't have adequate oxygen, we make lactate and that lactate is what causes the burn that we feel. And we've thought about it traditionally as a waste product. There's been beautiful
所有这些能量并以 ATP 的形式可供使用。当没有氧气时，丙酮酸盐无法燃烧，然后它必须转化为乳酸。这就是为什么当我们运动时，我们的肌肉缺氧或没有足够的氧气，我们会产生乳酸，而乳酸正是导致我们感到烧灼感的原因。传统上我们认为它是一种废物。曾经有过美丽
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experiments done in the last 5 or 10 years. Joshua Benowitz, a friend of mine, a professor at Princeton, has done some of these that have demonstrated that lactate is a very important fuel on its own. The heart, for example, is quite good at consuming lactate and burning it. >> The heart can it seems like it's kind of like a it's got it's consuming a sort of like dog's breakfast of fuels. It likes lipids. It'll take
过去 5 年或 10 年进行的实验。我的朋友、普林斯顿大学教授约书亚·贝诺维茨（Joshua Benowitz）所做的一些研究表明，乳酸本身就是一种非常重要的燃料。例如，心脏非常擅长消耗乳酸并燃烧它。 >> 心脏似乎正在消耗一种像狗早餐一样的燃料。它喜欢脂质。这需要
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glucose. It likes lactate. anything that's good for us cuz that that keeps it beating no matter what the metabolic status of you know as long as we're alive we have something that it can burn and lactate is just an important mediator of carrying th that energy around >> it can be a fuel it can be a shuttle >> in the context of exercise in brain and I know this is we're not talking about actionables here but like
葡萄糖。它喜欢乳酸。任何对我们有好处的东西，因为无论你的新陈代谢状态如何，只要我们还活着，我们就有一些可以燃烧和乳酸的东西，它只是携带能量的重要媒介>>它可以是一种燃料，它可以是一个穿梭机>>在大脑锻炼的背景下，我知道这不是我们在这里谈论的可操作的事情，而是像
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I've mentioned before on this podcast like if we do like an intense typically it's aerobic exercise we get like enough lactate generated that does seem to be a signal to the brain for this brain derived neutrophic factor which now kind of makes sense in this context because the whole purpose of BDNF is to build more stuff more connections typically rather than break connections so it's amazing that we think of these
我之前在这个播客中提到过，如果我们确实喜欢剧烈的有氧运动，我们会产生足够的乳酸，这似乎是大脑衍生的中性营养因子的信号，在这种情况下现在有点有意义，因为 BDNF 的整个目的是建立更多的东西，更多的连接，而不是破坏连接，所以令人惊讶的是，我们想到这些
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things like a waste product just like we used to talk about like junk DNA nobody does that [clears throat] anymore we have to be very careful with language in biology I'm realizing >> like the moment we we label something conceptually >> you like shut down a field like line of discovery that almost always ends up being like super important. >> Yeah, we joke all the time in the mitochondria field about the powerhouse
像废物之类的东西就像我们以前谈论的垃圾 DNA 一样没有人这样做[清嗓子]我们必须非常小心生物学中的语言我意识到>>就像我们在概念上标记某些东西的那一刻>>你喜欢关闭一个像发现线这样的领域，而它几乎总是最终变得非常重要。 >> 是的，我们在线粒体领域一直开玩笑说“发电站”
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of the cell, right? Which it really is. I mean, the cell the mitochondria are very good at being a powerhouse and making ATP, but they do so much more. And again, just to illustrate the point that when we categorize something into one thing, this is what it does. We're almost always proven wrong and it turns out to be a bit more complicated. There's something I can't wrap my head around because if I have an excess
细胞的，对吗？确实如此。我的意思是，细胞线粒体非常擅长成为发电站并制造 ATP，但它们的作用远不止于此。再次，只是为了说明这一点，当我们将某物归类为一件事时，这就是它的作用。我们几乎总是被证明是错误的，而且事实证明事情有点复杂。有些事我无法理解，因为如果我有多余的东西
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of energy and therefore I'm making lactate, am I going to now prioritize lactate? Is that going to now get burned off the top of the energy uh priority scale? >> That's a good question. And and you know, I I don't think we have strict answers to this, but there's definitely prioritization of energy. One of the most important things to burn is fatty acids. And and the reason for that is that when fatty acids are in
能量，因此我正在制造乳酸，我现在要优先考虑乳酸吗？现在它会被从能源呃优先级的顶部烧掉吗？ >> 这是个好问题。你知道，我认为我们对此没有严格的答案，但能源绝对是优先考虑的。最重要的燃烧物质之一是脂肪酸。其原因是当脂肪酸存在时
讲话人（自动字幕未标注）：
excess, they can be toxic. and they can be toxic in an acute way quickly. Glucose again is toxic in excess but chronically maybe it's a little bit less dangerous if we have high glucose for for some time. High free fatty acids is dangerous now >> and not just because it clogs arteries >> that of course. Yeah, exactly. >> Yeah, >> it Yeah, in reason in ways that we probably don't need to get into, but can be
过量，它们可能有毒。它们很快就会产生急性毒性。过量的葡萄糖同样是有毒的，但从长远来看，如果我们一段时间处于高血糖状态，危险可能会小一些。高游离脂肪酸现在很危险>>当然不仅仅是因为它会堵塞动脉>>。是的，完全正确。 >> 是的，>> 是的，以合理的方式，我们可能不需要进入，但可以
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讲话人（自动字幕未标注）：
disruptive to cell structures and so forth. And so, you know, most cells when they have fatty acids will burn the fatty acids first probably as a response to, hey, this could kill us. Let's let's take care of this first. >> Is also true the fatty acids we ingest. >> This is also true. The fatty acids we ingest if they get into cells, of course, you know, um you could imagine, again, it's a little more complicated
破坏细胞结构等。所以，你知道，大多数细胞在含有脂肪酸时会首先燃烧脂肪酸，这可能是对“嘿，这可能会杀死我们”的反应。让我们先解决这个问题。 >> 我们摄入的脂肪酸也是如此。 >> 这也是事实。我们摄入的脂肪酸，如果它们进入细胞，当然，你知道，嗯你可以想象，再说一次，它有点复杂
讲话人（自动字幕未标注）：
than this, but the fatty acids we ingest and the fatty acids we make end up in the same pathways, right? They they both get into other cells. uh throughout the body and when they do they need to be handled appropriately. Lactate is maybe a little bit more on that on that side. It has some important effects to the chemistry of cells that are important to deal with. And so lactate if it if it gets too high in the body
比这更重要的是，我们摄入的脂肪酸和我们制造的脂肪酸最终会进入相同的途径，对吗？它们都进入其他细胞。嗯，遍布全身，当它们发生时，需要适当处理。在那一侧，乳酸可能会多一些。它对细胞化学有一些重要的影响，需要处理。如果体内的乳酸含量过高
讲话人（自动字幕未标注）：
it can be toxic. you know, uh, lactic acidosis, which is essentially the the the phenomenon where we have too much lactic acid, lactate in our in our circulation. That's bad and can be lethal. And so, dealing with that lactate is important. And so, yeah, I think there is a prioritization that probably comes as a result of evolutionary pressure. You know, we had ancestors that maybe didn't deal with fatty acids so
它可能有毒。你知道，呃，乳酸性酸中毒，本质上是我们的循环中乳酸过多的现象。这很糟糕，而且可能是致命的。因此，处理乳酸很重要。所以，是的，我认为存在一个优先顺序可能是进化压力的结果。你知道，我们的祖先可能不处理脂肪酸，所以
讲话人（自动字幕未标注）：
well and maybe didn't survive, but we had one individual that figured out how to deal with them more effectively and that individual survived better and and that trait was selected for and we're now pretty good at it. We had a colleague of yours on the podcast who studies hypoxia and spleen function and and we're talking about how everyone hears the word mutation >> and they think like oh mutations are just always
好吧，也许没有生存下来，但我们有一个人知道如何更有效地处理他们，并且那个人生存得更好，而且这个特征被选择了，我们现在非常擅长。我们在播客上有一位研究缺氧和脾功能的同事，我们正在谈论每个人如何听到“突变”这个词>>，他们认为哦，突变总是如此
讲话人（自动字幕未标注）：
damaging but you know these mutations that afford more life that are adaptive essentially people can't hear that enough mutations are the reason we're here. >> That's right. >> Yeah. So the X-Men had it right. Like that's a that's a good series to watch. on the other side of the coin, the maladaptive um situation. Could you tell us about the Warberg effect and its role in cancer? And and I do want to frame this
具有破坏性，但你知道这些突变可以提供更多的生命，本质上是适应性的，人们听不到足够的突变是我们在这里的原因。 >> 没错。 >> 是的。所以 X 战警是对的。就像这是一个值得一看的好系列。另一方面，是适应不良的情况。您能告诉我们沃伯格效应及其在癌症中的作用吗？我确实想把这个框起来
讲话人（自动字幕未标注）：
properly because nowadays we're living in a weird time around this topic of cancer. There are these corners of the internet that like don't actually believe in cancer or germ theory. They they just like don't believe it. And some of that is actually kind of catching on. I believe cancer exists and I believe that cancers can come about through a variety of mechanisms. So only if you believe that to be true that it
正确的是，因为现在我们生活在一个围绕癌症话题的奇怪时代。互联网上有一些人实际上并不相信癌症或细菌理论。他们只是喜欢不相信而已。其中一些实际上很流行。我相信癌症的存在，并且癌症可以通过多种机制发生。所以只有当你相信这是真的
讲话人（自动字幕未标注）：
can come about through a variety of mechanisms. Would I ask you to like >> agree uh if you disagree please disagree but >> it's true right that there are a lot of paths to cancer. >> Yeah there's no question that there are some fundamental features of cancer. All cancers to my knowledge have mutations in the genome and those mutations are many but tend to cause again work together to cause that cell to divide to
可以通过多种机制实现。我想请您喜欢>>同意呃如果您不同意请不同意但是>>确实有很多通往癌症的途径。 >> 是的，毫无疑问癌症有一些基本特征。据我所知，所有癌症的基因组中都有突变，这些突变很多，但往往会再次共同作用，导致细胞分裂
讲话人（自动字幕未标注）：
replicate itself more rapidly to evade the immune system which is patrolling looking for misbehaving cells to eliminate them and somehow cancer cells can avoid that. critically important and you know one of the most um exciting developments in cancer therapy over the last 10 or 15 years has been these checkpoint inhibitors PD1 PDL1 that uh inhibitors that basically reverse that you know cancer cells are very good at
更快地自我复制以逃避正在巡逻的免疫系统，寻找行为不当的细胞来消灭它们，而癌细胞可以以某种方式避免这种情况。至关重要的是，你知道过去 10 或 15 年癌症治疗中最令人兴奋的发展之一就是这些检查点抑制剂 PD1 PDL1，这些抑制剂基本上可以逆转癌细胞非常擅长的功能
讲话人（自动字幕未标注）：
cloaking themselves let's say from the immune system and those therapies eliminate that cloak and and allow them to be seen by the immune system and eliminated and there's just been amazing responses to those new therapies again they don't treat every cancer to the same degree, but there's been wonderful examples where they've been effective. So yeah, cancers can arise through many different pathways. They all are
让我们说，这些疗法消除了免疫系统的伪装，让它们被免疫系统发现并消除，这些新疗法产生了惊人的反应，它们并没有以同样的程度治疗每种癌症，但有一些很好的例子表明它们是有效的。所以，是的，癌症可以通过许多不同的途径产生。他们都是
讲话人（自动字幕未标注）：
associated with mutations. One of the common features of cancer is changes in metabolism. And this is when you talk about the Warberg effect, this is really fundamentally what you're talking about. So the Warberg effect is a phenomenon that was named after Otto Warberg, a scientist, a German scientist back in the 1920s that observed that cancer cells consumed less oxygen than would be expected from the cells around
与突变有关。癌症的共同特征之一是新陈代谢的变化。这就是当你谈论沃伯格效应时，这实际上是你所谈论的根本问题。因此，沃伯格效应是一种以科学家奥托·沃伯格 (Otto Warberg) 的名字命名的现象，他是 20 年代的德国科学家，他观察到癌细胞消耗的氧气比周围细胞消耗的氧气少
讲话人（自动字幕未标注）：
them. And that has been named the Warberg effect. What Otto Warberg thought was that that's because the mitochondria are broken and then concluded that broken mitochondria are probably the cause of cancer. That was the thinking that permeated from the time of Otto Warberg in the 1920s for for many years. >> Broken meaning they're not making ATP or or they're they're doing something wacky. >> Yeah, they're well
他们。这被称为沃伯格效应。奥托·沃伯格认为这是因为线粒体被破坏了，然后得出结论，线粒体被破坏可能是癌症的原因。这是从 20 年代奥托·沃伯格时代起就渗透了很多年的思想。 >> 破碎意味着他们没有制造 ATP 或者他们正在做一些古怪的事情。 >> 是的，他们很好
讲话人（自动字幕未标注）：
they're not consuming oxygen. That was the observation. the oxygen consumption was low and that is again mitochondria as the powerhouse of the cell are consuming oxygen that's how they're doing their powerhouse function making ATP so that was the observation the interpretation of that observation was that mitochondria are probably broken we now know we've talked about this that mitochondria do more than just make
他们不消耗氧气。这就是观察结果。耗氧量低，这又是线粒体，因为细胞的动力室正在消耗氧气，这就是它们如何发挥其动力室功能来制造 ATP，所以这就是观察结果，对该观察结果的解释是线粒体可能被破坏了，我们现在知道我们已经讨论过，线粒体的作用不仅仅是制造 ATP
讲话人（自动字幕未标注）：
ATP and it turns out that mitochondria and cancer cells are not broken in fact they're very very good not necessarily at making ATP but at making stuff and again the stuff is what's so important for a cancer cell because it needs to divide itself it needs to duplicate itself to eventually make a tumor so the Warberg effect is a phenomenon again in simple terms that is absolutely the case that mo many cancer cells
ATP，事实证明，线粒体和癌细胞没有被破坏，事实上，它们非常非常擅长，不一定擅长制造 ATP，而是制造东西，而这些东西对癌细胞来说非常重要，因为它需要自我分裂，需要自我复制，最终形成肿瘤，所以沃伯格效应又是一种现象，简单来说，这绝对是大多数癌细胞的情况
讲话人（自动字幕未标注）：
most tumors consume less oxygen than you would imagine because they're instead of burning their fuel again we talked about this bifurcation cancer cells tend to not be burning. And by burning, that's consuming oxygen, but they're using their resource allocation to build stuff, to build a new cell. And so, I think this dubtales very nicely with what we've been talking about before. The oxygen consumption, the Warberg
大多数肿瘤消耗的氧气比你想象的要少，因为它们不再燃烧燃料，我们谈到了这种分叉癌细胞往往不会燃烧。通过燃烧，会消耗氧气，但他们正在利用资源分配来建造东西，建造新的细胞。所以，我认为这个故事与我们之前讨论的内容非常吻合。瓦伯格耗氧量
讲话人（自动字幕未标注）：
effect, is basically just a surrogate for that resource allocation question. And cancer cells are are very adept at using their resources to duplicate themselves. >> Of the uh modern treatments for cancer, radiation, chemotherapy and amunotherapies and what's of happening now had someone on talking about you know cart cells and um things of that sort. But is there anything that um you kind of sense on the horizon?
效应，基本上只是资源分配问题的替代。癌细胞非常善于利用它们的资源来复制自己。 >> 呃现代癌症治疗、放射、化疗和免疫疗法以及现在正在发生的事情有人在谈论你知道车细胞和诸如此类的事情。但你有什么感觉即将到来吗？
讲话人（自动字幕未标注）：
it might be 5 10 years out or two years out that like if if we could just solve that that we would be in a position to treat and cure many more cancers like like what's the >> what's the kind of lynchpin thing here? Is it being able to reallocate the use of pyuvate like if we could do that if that was a druggable thing or you could do a gene therapy but or you could use non-invasive tools like ultrasound or light
可能需要 5 年、10 年或两年后，如果我们能够解决这个问题，我们就能够治疗和治愈更多的癌症，就像 >> 这里的关键是什么？是否能够重新分配丙酮酸的使用，就像我们可以这样做，如果这是一种可药物的东西，或者你可以进行基因治疗，或者你可以使用超声波或光等非侵入性工具
讲话人（自动字幕未标注）：
these are all just forces right chemical or I would I would like to simplify things like for people if possible like there two ways to change things in the body healthy or unhealthy you have mechanical choices and chemical choices right you can feel more full by having your gut distend you can feel more full because your hypothalamus says you're full and there's a bunch of other stuff involved But like that's all
这些都是正确的化学力量，或者我想简化一些事情，比如对于人们来说，如果可能的话，有两种方法可以改变身体健康或不健康的情况，你有机械选择和化学选择，对吧，你可以通过让你的肠道扩张来感觉更饱，你可以感觉更饱，因为你的下丘脑说你已经吃饱了，还有很多其他的东西参与其中，但就这样了
讲话人（自动字幕未标注）：
we've got is mechanical and chemical forces. >> So let's assume you had the tool. >> Is there some place where like you feel like if we could just >> turn that bolt? >> Yeah. >> We would be in a much better position to treat a lot of cancers or cure them. >> Let's maybe take a step back from that and then get to that question in a second and talk about cancer. You know what it is and why it's so difficult. If a
我们有的是机械力和化学力。 >> 因此，我们假设您拥有该工具。 >> 有没有像您一样的地方，我们可以>> 转动那个螺栓？ >> 是的。 >> 我们将能够更好地治疗或治愈许多癌症。 >> 让我们先退后一步，然后再讨论这个问题，谈谈癌症。你知道它是什么以及为什么如此困难。如果一个
讲话人（自动字幕未标注）：
bacteria invades us, it's very easy for our immune system to say, "Hey, that's not us. Let's go kill that thing." >> If a cancer cell starts hyperp proliferating, it's us, right? It's our cells. It doesn't have antigens, which are the technical term for the molecules, the features that are recognized by the immune system. it doesn't necessarily have antigens that are recognized as not us nonself. So that's one of
当细菌入侵我们时，我们的免疫系统很容易说：“嘿，那不是我们。我们去杀死那个东西吧。” >> 如果癌细胞开始过度增殖，那就是我们，对吧？这是我们的细胞。它没有抗原，这是分子的技术术语，是免疫系统识别的特征。它不一定具有被识别为非我们非自身的抗原。所以这是其中之一
讲话人（自动字幕未标注）：
the big challenges of cancer. The challenge for us is to figure out a way to kill those cells which again are our cells. They are us to kill those cells without killing the rest of our cells. Because if we kill the rest of our cells, we kill us, right? That's the challenge of cancer therapy in my view. Again, I'm oversimplifying, but that's that's a big challenge. And many of the features of cancer cells are not
癌症的巨大挑战。我们面临的挑战是找到一种方法来杀死这些细胞，而这些细胞又是我们的细胞。他们是我们杀死这些细胞而不杀死我们其余细胞的。因为如果我们杀死了其余的细胞，我们就杀死了我们自己，对吗？在我看来，这就是癌症治疗的挑战。再说一次，我过于简单化了，但这就是一个巨大的挑战。癌细胞的许多特征并不具有
讲话人（自动字幕未标注）：
completely new things that that cancer just invented. It's using the functions that our normal cells have. For example, one of the things that's common, not universal, but common in cancer cells is to become more like a stem cell. Has many features of stem cells. So, okay, we can find a way to target a specific stem cell pathway and kill all the cells that have that. Well, then we're killing many of our stem cells,
癌症刚刚发明的全新事物。它利用了我们正常细胞所具有的功能。例如，在癌细胞中常见但不普遍但常见的事情之一是变得更像干细胞。具有干细胞的许多特征。所以，好吧，我们可以找到一种方法来针对特定的干细胞途径并杀死所有具有该途径的细胞。好吧，那么我们正在杀死许多干细胞，
讲话人（自动字幕未标注）：
too. And now the lining of our gut doesn't regenerate, which we talked about. That's driven by hair. Exactly. This is obviously one reason why many of the the side effects of chemotherapy is to target those proliferating cells which share many features with cancer cells. So that's the problem of cancer therapy. And there's a second problem that's worth talking about too. We've talked about evolution a lot here which
也。现在我们的肠道内壁无法再生，正如我们所讨论的。这是由头发驱动的。确切地。显然，这就是为什么化疗的许多副作用都是针对那些与癌细胞有许多共同特征的增殖细胞的原因之一。这就是癌症治疗的问题。还有第二个问题也值得讨论。我们在这里谈论了很多进化论
讲话人（自动字幕未标注）：
I think is it's a great rubric by which to think about biology. Cancer cells a a tumor is under evolutionary pressure. Right? So we know let's take an example where we have a tumor and we get a drug. We have a great drug that kills 99.9% of the cells in that tumor. But.1% of the cells either through a mutation or some sort of an adaptation are not killed by it. But that.1% can now repopulate, make a new tumor. And
我认为这是思考生物学的一个很好的标准。癌细胞和肿瘤面临着进化压力。正确的？所以我们知道让我们举一个例子，我们患有肿瘤并且我们得到了药物。我们有一种很棒的药物，可以杀死肿瘤中 99.9% 的细胞。但是，有 1% 的细胞通过突变或某种适应而不会被它杀死。但那 1% 现在可以重新生长，形成新的肿瘤。和
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讲话人（自动字幕未标注）：
this is what happens in cancer therapy. We all know of tragic examples where we loved ones had a tumor, got a treatment and they went into remission. you know, the tumor maybe shrinks, it goes away, maybe even becomes invisible by the imaging tools that we have to image uh cancers, but then it comes back. And that's because these cells are under evolutionary pressure. If if one cell, theoretically, one cell acquires
这就是癌症治疗中发生的情况。我们都知道一些悲惨的例子，我们所爱的人患有肿瘤，接受治疗后病情得到缓解。你知道，肿瘤可能会缩小，消失，甚至可能通过我们对癌症进行成像的成像工具变得不可见，但随后它又会回来。那是因为这些细胞面临着进化压力。如果一个细胞，理论上，一个细胞获得
讲话人（自动字幕未标注）：
a mutation that makes it resistant to that drug, doesn't get killed by that drug, that one cell can now repopulate, make a new tumor, and be just as damaging. And now it's resistant to the drug. Now the drug doesn't work anymore. And this is the second big problem with cancer therapy. You know I this is not my field of expertise per se but I feel like given that situation this is not dissimilar to what happens with
一种突变使其对该药物产生抗药性，不会被该药物杀死，一个细胞现在可以重新繁殖，产生新的肿瘤，并且具有同样的破坏性。现在它对药物产生了耐药性。现在药已经没有作用了。这是癌症治疗的第二大问题。你知道，这本身不是我的专业领域，但我觉得考虑到这种情况，这与发生的情况没有什么不同
讲话人（自动字幕未标注）：
viruses. HIV now can be managed and frequently is managed by a triple combination therapy. And the reason for that is you now give three drugs that are going to kill that virus or prevent the propagation of that virus. It's now very difficult to acquire resistance to all three simultaneously. I think the analogy applies to cancer too. I think the future of cancer therapy again in my in my worldview is going to be we
病毒。现在，艾滋病毒可以得到控制，并且通常可以通过三重联合疗法来控制。原因是你现在给予三种药物来杀死该病毒或阻止该病毒的传播。现在很难同时获得对这三者的抵抗力。我认为这个类比也适用于癌症。我认为在我的世界观中，癌症治疗的未来将是我们
讲话人（自动字幕未标注）：
have many safe and effective drugs that hit different features of the cancer cells biochemistry and by virtue of understanding the specifics of the tumor that I might have the astute oncologist can say given that unique biochemistry of that tumor this drug this drug and this drug are going to work together to kill that tumor. And it's going to be very hard for that tumor to become resistant to all of those drugs
有许多安全有效的药物可以针对癌细胞生物化学的不同特征，并且通过了解肿瘤的具体情况，精明的肿瘤学家可以说，鉴于该肿瘤独特的生物化学，这种药物和这种药物将共同杀死该肿瘤。肿瘤很难对所有这些药物产生耐药性
讲话人（自动字幕未标注）：
simultaneously and as a result of that that might result in something approximating a cure. I think that's the world that we need to get to. So there's been amazing therapies that have come out. You know, one of the most exciting recently are drugs that target specific encogenic mutations, specific mutations that cause cancer. Krass mutations are one that that are really exciting that target specific proteins that
同时并因此可能会导致某种接近治愈的结果。我认为这就是我们需要到达的世界。因此，出现了一些令人惊奇的疗法。您知道，最近最令人兴奋的药物之一是针对特定内源突变（导致癌症的特定突变）的药物。 Krass 突变是一种非常令人兴奋的突变，它针对特定的蛋白质，
讲话人（自动字幕未标注）：
are contributing to the cancer in a completely specific way. Don't do anything else in the body to normal cells. Only hit those mutations that are onenic. But again, eventually there can be resistance that's acquired to that. So if we can now make multiple examples of that kind of specific safe kind of [snorts] drug and use them in combinations, our ability to treat cancer is going to be dramatically improved. >>
以完全特定的方式导致癌症。不要对体内的正常细胞做任何其他事情。只攻击那些单一的突变。但同样，最终可能会遇到阻力。因此，如果我们现在可以制作这种特定安全药物的多个例子并将它们组合使用，我们治疗癌症的能力将得到显着提高。 >>
讲话人（自动字幕未标注）：
That's very encouraging. We had a guy on the podcast named David Fagenbomb. He's a medical doctor. Are you familiar with his work? He's at University of Pennsylvania. He had Castleman's disease and he was able to cure his own Castleman's disease because he was basically on his deathbed. and he basically just started taking different combinations of already approved drugs in a kind of desperate attempt to save his
这非常令人鼓舞。我们的播客中有一位名叫大卫·法根博姆（David Fagenbomb）的人。他是一名医生。你熟悉他的作品吗？他在宾夕法尼亚大学。他患有卡斯尔曼氏病，并且能够治愈自己的卡斯尔曼氏病，因为他基本上已经濒临死亡。他基本上只是开始服用已经批准的药物的不同组合，绝望地试图挽救他的生命
讲话人（自动字幕未标注）：
life. And he he found things that would extend his life. And he's been alive 11 years now. and he runs a lab, serious scientist as we say, but he also has this uh not for profofit called Every Cure, which has been successfully using AI and cell assays and things to take biopsies and try and figure out like, okay, in this tragedy of a kid who's dying of a particular cancer, like let's just throw a bunch of not random
生活。他发现了可以延长他生命的东西。现在他已经活了 11 年了。他经营着一个实验室，正如我们所说，是一位严肃的科学家，但他也有一个名为“Every Cure”的非营利组织，它已经成功地使用人工智能和细胞分析以及进行活组织检查的东西，并尝试找出答案，就像，好吧，在这个死于某种特定癌症的孩子的悲剧中，就像让我们扔一堆非随机的
讲话人（自动字幕未标注）：
drugs, but already approved drugs at this tumor in a dish, and if some of them work, like if the parents agree and there's no other hope, do it. and like in some cases they're curing and in many cases they're extending life. It matches up well with what you're describing. It requires this AI piece to run iterations cuz there's a huge catalog of drugs that even oncologists might not be aware of. One particular
药物，但已经批准在培养皿中治疗该肿瘤的药物，如果其中一些有效，例如如果父母同意并且没有其他希望，那就去做。就像在某些情况下它们正在治愈，而在许多情况下它们正在延长生命。与你所描述的情况非常吻合。它需要这个人工智能片段来运行迭代，因为有大量的药物目录，甚至连肿瘤学家也可能不知道。一个特别的
讲话人（自动字幕未标注）：
highlight of his work is that we know now that in breast cancers where they use lidocaine during the surgery the incidences of recurrence are significantly lower. >> And it turns out that lidocaine has some effect on the local environment. I'm not, this isn't my area, but you know, David talks about this and I'm encouraged by things like that and what you're describing that we're not necessarily going to have like
他工作的亮点是我们现在知道，在乳腺癌手术中使用利多卡因，复发率显着降低。 >> 事实证明，利多卡因对当地环境有一定影响。我不是，这不是我的领域，但你知道，大卫谈到了这个，我对类似的事情以及你所描述的我们不一定会遇到的事情感到鼓舞
讲话人（自动字幕未标注）：
the miracle drug, but then the miracle cocktail for that individual, that cancer. >> That's the key thing is that, you know, >> David's situation is very specific to David and and every tumor is a little bit different. >> Yeah. And one of I think the unhelpful results of historically how we talk about tumors is we talk about breast cancer or liver cancer or you know colon cancer. There are some breast cancers that
神奇的药物，然后是针对那个人的神奇鸡尾酒，即癌症。 >> 关键是，你知道，>> 大卫的情况非常特殊，而且每个肿瘤都有点不同。 >> 是的。我认为历史上我们谈论肿瘤的无益结果之一是我们谈论乳腺癌或肝癌，或者你知道结肠癌。有一些乳腺癌
讲话人（自动字幕未标注）：
are more similar to some liver cancers than they are to other breast cancers. Right? This is our historical classification of cancer has just been by where it is. was defined by the surgeons that would take it out. But the specific mutations that cause that cancer and keep that cancer again evading the immune system, propagating, avoiding cell death and so forth are unique to that cancer. So if we understand the
与其他乳腺癌相比，它们与某些肝癌更相似。正确的？这是我们对癌症的历史分类。是由将其取出的外科医生定义的。但导致该癌症并使该癌症再次逃避免疫系统、传播、避免细胞死亡等的特定突变是该癌症所独有的。所以如果我们理解
讲话人（自动字幕未标注）：
unique mutational landscape of that cancer that gives us then an ability to say again in a in a world that isn't today's world but hopefully not too long uh far from now where we have the ability to say this combination of drugs is going to be effective at killing the cells in that tumor. You're highlighting something really important that is both about the sociology of medicine and science that it's just the it's
这种癌症独特的突变景观使我们有能力在一个不是当今世界的世界中再说一次，但希望不会太久远，距离现在我们有能力说这种药物组合将有效杀死该肿瘤中的细胞。你强调了一些关于医学社会学和科学社会学的非常重要的事情，它只是
讲话人（自动字幕未标注）：
not disparaging of it's just it is the way it is because of history. So much of the way things are in medicine and science can be answered by the a phrase that everyone should hate, which is, well, we've always done it that way, which is the worst reason to do anything unless it's working spectacularly well, right? But is it a stretch to say that there are some liver cancers that are called liver cancer but that are
并不是贬低它，只是因为历史，它就是这样。医学和科学中的很多事情都可以用每个人都应该讨厌的一句话来回答，那就是，好吧，我们一直都是这样做的，这是做任何事情的最糟糕的理由，除非它运作得非常好，对吧？但是，有些肝癌虽然名为肝癌，但其实是肝癌，这样说是否有些牵强？
讲话人（自动字幕未标注）：
actually much closer in terms of their cellular phenotype to cancer of a cardiammyioite because of the way that say MPC one is changed in other words like should we be classifying cancers as oh this is a cancer of the sort that the cells are making too much of themselves. >> Yeah. >> As opposed to they're overusing energy. There's too much pyuvate. I'm making this up, right? I'm not obviously not my field. But
实际上，就其细胞表型而言，它们与心肌细胞的癌症更接近，因为 MPC 的改变方式换句话说，就像我们应该将癌症分类为哦，这是一种细胞过度利用自身的癌症。 >> 是的。 >> 而不是他们过度使用能源。丙酮酸盐太多了。我正在编造这个，对吗？我显然不是我的领域。但
讲话人（自动字幕未标注）：
rather than think only about address in the body. >> Yeah, no question that we should be thinking about the specific features of cancer. I've been talking about it in terms of the mutation, >> the specific mutations that define a cancer. And I think that's a useful way to do it >> because those mutations in a way are the instructions for making a new cell. Right? the genome of a cell are the instructions for how to
而不是只考虑正文中的地址。 >> 是的，毫无疑问我们应该考虑癌症的具体特征。我一直在谈论突变，>>定义癌症的特定突变。我认为这是一种有用的方法>>因为这些突变在某种程度上是制造新细胞的指令。正确的？细胞的基因组是如何进行操作的指令
讲话人（自动字幕未标注）：
make a new cell, the the constituents that would make up a new cell. But I think a very important feature that you're touching on that I appreciate you bringing up is on top of that, layered on top of that is the unique metabolism that makes up that cell, right? That enables those instructions to be executed. You know, a cell can have all the right instructions to make a new cell, but if it doesn't have the building
制造一个新细胞，即构成新细胞的成分。但我认为你提到的一个非常重要的特征，我很欣赏你提出的，是最重要的，最重要的是构成该细胞的独特的新陈代谢，对吗？这使得这些指令能够被执行。你知道，一个细胞可以拥有制造新细胞的所有正确指令，但如果它没有建筑物
讲话人（自动字幕未标注）：
blocks, the lumber and the bricks and the mortar to make a new cell, it can't make a new cell. And so, I think that's a really important feature of this that we need to talk about. And there's been a lot of energy in the in the field over the last 10 or 15 years and maybe even 10 years or less at trying to specifically block the resource allocation of cancer cells toward building new new cells. The challenge there
块、木材、砖块和砂浆来制造一个新的细胞，但它不能制造一个新的细胞。因此，我认为这是我们需要讨论的一个非常重要的特征。在过去的 10 年或 15 年，甚至可能是 10 年或更短的时间里，该领域投入了大量的精力，试图专门阻止癌细胞的资源分配以构建新的新细胞。那里的挑战
讲话人（自动字幕未标注）：
again is that it's fairly easy to develop resistance to that. A cancer cell can just make a mutation and and rewire its metabolism to build that same thing a different way. But that is a very important feature of the cancer tube. Beyond just the mutations are the are the the metabolic processes that enable those mutations to be manifest in in in what turns into a tumor. How far are we from a a world where um I drink
再次是，很容易对此产生抵抗力。癌细胞可以发生突变并重新连接其新陈代谢，以不同的方式构建相同的东西。但这是癌管的一个非常重要的特征。除了突变之外，还有使这些突变在形成肿瘤的过程中表现出来的代谢过程。我们离一个我喝酒的世界还有多远
讲话人（自动字幕未标注）：
a fluid and it's a safe fluid because we do this for like other types of imaging. I step into a tube and I do it when I'm like five >> and I do it when I'm 50. >> Mhm. And I get a picture of red and green in every cell, right? So you get like an image of like the proportion of my metabolism in different organs and you could zoom in to a single cell. This is not like science fiction at the level like it couldn't be
一种液体，它是一种安全的液体，因为我们这样做是为了像其他类型的成像一样。我走进一个管子，当我五岁的时候我就会这样做>>，当我 50 岁的时候我也会这样做。>>嗯。我在每个单元格中都得到了红色和绿色的图片，对吧？所以你会得到一幅不同器官中新陈代谢比例的图像，你可以放大到单个细胞。这不像科幻小说那样不可能
讲话人（自动字幕未标注）：
done >> where you say okay this is a healthy cardommyioite and it's using 65% of its energy to just keep pumping and then it like puts aside a little bit to make sure it can make more of its stuff so it stays around and a little bit. it's like going to this other pathway and like that's a healthy cardio. We know this from the population of of age match data and then when I'm you know 40 50 you go yeah I don't know
完成 >> 你说的好，这是一个健康的豆蔻石，它使用 65% 的能量来继续泵送，然后它会留出一点点，以确保它可以制造更多的东西，这样它就会留在周围，一点点。这就像走另一条路，就像这是一种健康的有氧运动。我们从人口年龄匹配数据中知道这一点，然后当我知道 40 50 时，你就走了，是的，我不知道
讲话人（自动字幕未标注）：
like the your heart's looking a little more green than red or something like that. we can kind of turn the dial back like like we have druggable, you know, targets inside of cells and we can like kind of like adjust the the energy allocation like is what I'm describing like so crazy because I can imagine a mouse experiment or paper will probably come out on that next week if it hasn't already >> and like that's kind
就像你的心看起来比红色更绿一点或者类似的东西。我们可以把旋钮调回来，就像我们有可药物的，你知道，细胞内的目标，我们可以像调整能量分配一样，就像我所描述的那样疯狂，因为我可以想象，如果还没有的话，下周可能会出现小鼠实验或论文，就像那样>>
讲话人（自动字幕未标注）：
of what you want. You want subcellular resolution cuz I feel like we've gone from this place where like >> I was around when the first MR like functional magnetic resonance imaging stuff was kind of like here's a person looking at a banana here's a person hearing a joke and like now you can see dynamics and you can see acts on pathways but if we get down to the cells cool >> it's a lot of salt and pepper >> then you
你想要什么。你想要亚细胞分辨率，因为我觉得我们已经离开了这个地方，就像 >> 当第一个类似功能性磁共振成像的东西出现时，我就在附近，就像这是一个人在看香蕉，这是一个人在听笑话，就像现在你可以看到动态，你可以看到通路上的行为，但如果我们深入细胞，冷静>>这是很多盐和胡椒>>然后你
讲话人（自动字幕未标注）：
get down to the inner workings of the cells you can't see everything if you look at everything it's going to look like chaos >> someone put on X this morning actually a AI I rendering of all the proteins in a cell in one tiny patch of cell and it's just like overwhelming. You're just like, "Oh my god." Like there's so much here. But if you just say like, "Let's just look at metabolism at this key node and we know
深入到细胞的内部运作，你无法看到一切，如果你观察一切，它看起来会像混乱一样 >> 今天早上有人戴上了 X，实际上是人工智能 I 在一小块细胞中渲染了细胞中的所有蛋白质，这就像压倒性的。你就像，“天哪。”好像这里有很多东西。但如果你只是说，“让我们看看这个关键节点的新陈代谢，我们就知道
02:00:00
讲话人（自动字幕未标注）：
what healthy should be. Here's where you're at." >> And you're just trying to tilt that balance. I mean, that to me feels like a >> that could be done. >> Yeah. >> Like we've got smart people working on this. We need more money >> to for scientists to work this stuff out and more scientists to do that work. But I feel like that's doable >> conceptually. Pieces of that are doable. I think you know when you talk about
健康应该是什么。这就是你现在所处的位置。” >> 而你只是想扭转这种平衡。我的意思是，对我来说，这感觉像是可以做到的。 >> 是的。>> 就像我们有聪明的人在研究这个问题。我们需要更多的钱>>让科学家们解决这个问题，需要更多的科学家来做这项工作。但我觉得从概念上讲这是可行的。其中的一些部分是可行的。我想当你谈论时你就知道了
讲话人（自动字幕未标注）：
can we basically image metabolism with cellular resolution I [clears throat] should be clear that's a very difficult problem. The spatial resolution the ability to see fine enough detail to make out individual cells or even uh smaller than that. That's a challenge. That's definitely a challenge inside a human body. And it's also a challenge to be able to have a surrogate of metabolism that we can actually see. Of
我们能用细胞分辨率基本上对新陈代谢进行成像吗？我[清嗓子]应该清楚这是一个非常困难的问题。空间分辨率能够看到足够精细的细节，以辨认出单个细胞，甚至比这更小的细胞。这是一个挑战。这绝对是人体内部的一个挑战。能够拥有我们实际看到的新陈代谢替代物也是一个挑战。的
讲话人（自动字幕未标注）：
course, our metabolism, there's nothing visual that we can see with the naked eye, right? That there's nothing I can see in the metabolism of a cell. So, what could we make that would enable us to visualize that? There's really exciting tools being developed of many different kinds to be able to image various features of metabolism in a cell. >> Well, we would in neuroscience. I mean, again, I was fortunate to be
当然，我们的新陈代谢，没有任何东西是我们肉眼可以看到的，对吧？我在细胞的新陈代谢中看不到任何东西。那么，我们可以做些什么来使我们能够想象这一点呢？许多不同类型的工具正在开发中，这些工具确实令人兴奋，能够对细胞中新陈代谢的各种特征进行成像。 >> 好吧，我们会在神经科学领域。我的意思是，我再次很幸运
讲话人（自动字幕未标注）：
part of this wave of technology. Didn't contribute to building any of it, but it was like, how do you know which brain areas are active? Well, you could drop electrodes in or you could remove a piece and go, well, it probably did that when it was there cuz you lost that function. But, you know, a lot of it was just blood flow. It was like oxygenated to deoxxygenated blood >> reflects light differently. And like
这波技术浪潮的一部分。没有为构建任何东西做出贡献，但就像，你怎么知道哪些大脑区域是活跃的？好吧，你可以把电极放进去，或者你可以取下一块然后走，好吧，它可能会那样做，因为你失去了那个功能。但是，你知道，很多只是血流。就像含氧血液和脱氧血液一样>>反射光的方式不同。并且喜欢
讲话人（自动字幕未标注）：
you'd get these beautiful maps, but you were just looking at blood flow. Now, then you got >> 2D deoxy glucose. You can look at glucose uptake, but it was spatially very crude or it was the the time resolution wasn't very good. But I feel like we've come some way. You can look at voltage. You can look at calcium. I feel like >> the moment that chemists, bioengineers, and physicists and computers came into biology,
你会得到这些漂亮的地图，但你只是在观察血流。现在，您得到>> 2D 脱氧葡萄糖。您可以查看葡萄糖的摄取，但它在空间上非常粗糙，或者时间分辨率不是很好。但我觉得我们已经取得了一些进展。你可以看看电压。你可以看看钙。我感觉>>化学家、生物工程师、物理学家和计算机进入生物学的那一刻，
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things got a lot better. >> Yeah. >> I mean, some people say it got a lot worse, >> but they retired now. So, like, it got a lot better because you could see what's really happening. >> Maybe I'm overly optimistic. No, I I think that we need to be able to figure out what to measure. I mean, that's obviously a key thing. What would be the metabolic parameter? What would be the one metabolic parameter you'd really
事情变得好多了。 >> 是的。 >> 我的意思是，有些人说情况变得更糟，>> 但他们现在退休了。所以，情况变得好多了，因为你可以看到到底发生了什么。 >>也许我过于乐观了。不，我认为我们需要弄清楚要衡量什么。我的意思是，这显然是一件关键的事情。代谢参数是什么？您真正想要的一个代谢参数是什么
讲话人（自动字幕未标注）：
want to measure to assess is this cell healthy or not healthy? And it's hard to know exactly what that one would be or collection of things and then figure out a way to measure that >> non-invasively, so to speak. You know, it's one thing if if I'm going to measure that, do I have to cut off my arm, >> shave it into slices, and you know, measure it? Nobody wants that. >> So, how can I measure it without, >> you
想要测量以评估该细胞是否健康？可以这么说，很难确切地知道那个东西是什么或东西的集合，然后找出一种非侵入性地测量它的方法。你知道，如果我要测量它，我是否必须切断我的手臂，>>将其切成片，然后测量它，这是一回事？没有人想要这样。 >>那么，如果没有>>你，我该如何测量它
讲话人（自动字幕未标注）：
know, doing damage to me while I'm measuring it? These are hard problems, but as you say, the technology just keeps getting better in all versions of this. And the experimental tools, the tools that we can use in mice or in cells and culture are definitely getting better. And that that's that's an aspect of this field of of studying metabolism that's really exciting is our ability to now be able to measure what's
你知道吗，在我测量的时候会对我造成伤害吗？这些都是难题，但正如你所说，技术在所有版本中都在不断进步。实验工具，我们可以在小鼠或细胞和培养物中使用的工具肯定会变得更好。这就是新陈代谢研究领域的一个方面，真正令人兴奋的是我们现在能够测量什么
讲话人（自动字幕未标注）：
happening at individual places in individual cells and looking at specific individual molecules you know intermediates and products and substrates of these this metabolic map and that I think is teaching us a lot about how metabolism works in individual cells and that is then going to be informative when we think about how it's working in a I'm intrigued by this really wild thing that you see in the news every once
发生在单个细胞的各个位置，观察特定的单个分子，你知道这些代谢图的中间体、产物和底物，我认为它教会了我们很多关于新陈代谢如何在单个细胞中工作的知识，当我们思考它是如何工作的时，这将提供信息。我对你每次在新闻中看到的这种非常疯狂的东西很感兴趣
讲话人（自动字幕未标注）：
in a while which I believe to be true but no one can explain which is that there are dogs and there are occasionally people who can detect the scent of cancer beyond chance like this is like no one really knows the basis of this and recently there's an example my understanding is it's validated of a woman who was able to smell Parkinson's as a musty scent that a musky excuse me and now spouses of people that had
有一段时间，我相信这是真的，但没有人能解释，那就是有狗，偶尔有人能够超越偶然地检测到癌症的气味，就像没有人真正知道其基础一样，最近有一个例子，我的理解是，它验证了一位女士能够闻到帕金森氏症的霉味，对不起，现在是那些患有帕金森病的人的配偶
讲话人（自动字幕未标注）：
Parkinson's in particular the female um the wives of these men like oh yeah I remember this now of course there's a whole lot of like placebo correlation just so story that can emerge from that but as you're telling me some of this like obviously you wouldn't want this to be the one and only frontline detection system but it kind of makes sense that if if cellar metabolism is at the heart of certain cancers or
帕金森氏症尤其是女性，这些男人的妻子，哦，是的，我现在当然记得这一点，当然有很多类似安慰剂的相关性，这样的故事就可以从中浮现出来，但正如你告诉我的一些内容，显然你不希望这是唯一的前线检测系统，但这有点有意义，如果细胞代谢是某些癌症的核心，或者
讲话人（自动字幕未标注）：
neurodeenerative conditions makes sense that we're breathing out yeah >> the byproducts obviously these sense are just correlative right and the shifts in when we with infants, parents are remarkably good at being like something's off because they can't communicate verbally with us yet, right? Like something's off in their stool or something's off in their skin power that's not extreme and and become remarkably
神经退行性病症是有道理的，我们正在呼气，是的>>副产品显然这些感觉只是相关的，当我们带着婴儿时，父母非常擅长表现得好像有些不对劲，因为他们还不能与我们进行口头交流，对吗？就像他们的粪便中有什么东西掉了，或者他们的皮肤力量有什么东西掉了，这不是极端的，并且变得非常明显
讲话人（自动字幕未标注）：
astute detecting real underlying issues. Yeah. So, do you think that there could be useful information coming from the air we expel in terms of revealing at a systemic level or maybe even at a cellular level um how well or poorly we're regulating >> energy? Yeah. I mean, obviously, as you said in your in in alluding to this, this is again at the frontier of science and I don't think we understand much of the
敏锐地发现真正的根本问题。是的。那么，您认为我们排出的空气中可能存在有用的信息，可以在系统水平甚至细胞水平上揭示我们对>>能量的调节程度如何？是的。我的意思是，显然，正如您在提到这一点时所说的那样，这又是科学的前沿，我认为我们对其中的了解不多
讲话人（自动字幕未标注）：
specifics, but I think you could imagine that because again, smells, scents are chemistry, right? These are chemical compounds that are coming from the person. And when a person's doing different metabolism, they're going to be producing different chemicals in different proportions. And I think it is possible that those can be detected in specific ways. That's not so dissimilar from some of the diagnostics that we
具体细节，但我想你可以想象，因为同样，气味、气味是化学，对吗？这些是来自人体的化合物。当一个人进行不同的新陈代谢时，他们会产生不同比例的不同化学物质。我认为这些可能可以通过特定的方式检测到。这与我们的一些诊断并没有什么不同
讲话人（自动字幕未标注）：
do use where we actually measure the blood chemistry. You know, the blood chemistry is different between people that have different diseases and don't. And so, you know, and obviously the breath is some measure of the chemistry that's going on in the person. It's obviously um different from the blood, but it's a fascinating topic and and as that gets to chemical specificity, it'll become probably more clear what's
请在我们实际测量血液化学成分的地方使用。您知道，患有不同疾病和未患有疾病的人之间的血液化学成分是不同的。所以，你知道，显然呼吸是人体内发生的化学反应的某种衡量标准。它显然与血液不同，但这是一个令人着迷的话题，随着化学特异性的增加，它可能会变得更加清楚是什么
讲话人（自动字幕未标注）：
going on there and why why is Parkinson specifically susceptible to that different chemistry in a way that can be detected by scent. We were talking a few moments ago about excess energy toxicity. This is something that Dr. Lane Norton brought up on this podcast. He's a serious biochemist, nutrition, exercise science guy, public educator, loves random ice control trials and metaanalysis. That's like his if it's not
那里发生了什么，以及为什么帕金森病特别容易受到这种不同化学物质的影响，并且可以通过气味检测到。刚才我们正在谈论能量过剩的毒性。这是莱恩·诺顿博士在这个播客中提出的。他是一位认真的生物化学家、营养学、运动科学专家、公共教育家，喜欢随机冰控制试验和荟萃分析。这就像他的，如果不是的话
讲话人（自动字幕未标注）：
there, he's not interested or he's perfectly interested in in tossing away everything else. So that's kind of his hallmark. So that should feel good to you just knowing that. But he talks about this energy toxicity. You know, like excess calories leads to problems. Not just because of the presence of excess body fat, but because of just too much energy at the front end creates downstream biochemical issues across
在那里，他对扔掉其他一切不感兴趣或者完全感兴趣。这就是他的标志。所以知道这一点你应该感觉很好。但他谈到了这种能量毒性。你知道，过量的卡路里会导致问题。不仅是因为身体脂肪过多，而且前端能量过多会导致下游生化问题
讲话人（自动字幕未标注）：
the body. How does this relate to some of what we've been discussing? >> There's a a widely accepted hypothesis that mitochondria with excess energy leads to problems. You know, many people that that are listening have probably heard of reactive oxygen species. This is, you know, forms of oxygen that become reactive and end up spinning out and damaging proteins and nucleic acids. And I think it is uh again widely
身体。这与我们一直在讨论的一些内容有何关系？ >> 有一个广泛接受的假设，即线粒体能量过剩会导致问题。您知道，许多正在听的人可能听说过活性氧。你知道，这是氧气的形式，它们会变得活跃，最终旋转出来并破坏蛋白质和核酸。我认为这又是广泛的
讲话人（自动字幕未标注）：
accepted, not universally, but widely accepted that one of the contributors to that is mitochondria that have too much energy. Basically, the form that energy takes when it's extracted from the food we eat and before it's converted to ATP is powering the mitochondria. And when that mitochondria is overpowered, that leads to a state that is very susceptible to generation of these reactive species that end up damaging
人们普遍认为，造成这种情况的原因之一是能量过多的线粒体，这一点虽然不是普遍接受，但已被广泛接受。基本上，从我们吃的食物中提取能量并在转化为 ATP 之前所采取的能量形式为线粒体提供动力。当线粒体被压倒时，就会导致一种非常容易产生这些反应性物质的状态，这些反应性物质最终会造成损害
讲话人（自动字幕未标注）：
our genome, creating mutations and damaging proteins and creating many of the problems that we see. And I think there's been a number of studies that have suggested they might contribute to various pathologies including aging. So I think that idea of excess energy is one that is really important to consider from the level of the organism down to the level of individual cells and even the mitochondria within those
我们的基因组，产生突变并破坏蛋白质，并造成我们看到的许多问题。我认为有许多研究表明它们可能会导致包括衰老在内的各种病症。因此，我认为能量过剩的概念是一个非常重要的概念，从生物体的水平到单个细胞的水平，甚至是细胞内的线粒体。
讲话人（自动字幕未标注）：
cells. Once again, it I'm thinking about the this notion like no individual or collection of individuals or cell or collection of cells can really get away with or what's the saying like you pay the piper somehow. Like cells really get punished for cheating themselves by taking too much energy or not allocating it correctly. Like you can level up >> from this like single cell analysis all the way to to societies. I
细胞。我再一次思考这个概念，比如没有任何个人或个人集合或细胞或细胞集合可以真正逃脱惩罚，或者什么叫你以某种方式付钱给风笛手。就像细胞因为消耗过多能量或不正确分配能量而欺骗自己一样，确实会受到惩罚。就像你可以从单细胞分析一直升级到社会一样。我
讲话人（自动字幕未标注）：
actually think >> this is fascinating. I for a variety of reasons. First of all, again, we've never had a serious discussion about what mitochondria actually do besides just create help create energy. So, first of all, thank you so much for telling us how they actually allocate their resources towards things other than just making more energy for usage to build more of oneself. also for framing that in the context
实际上认为>>这很有趣。我因为种种原因。首先，我们从来没有认真讨论过线粒体除了创造能量之外实际上还能做什么。因此，首先，非常感谢您告诉我们他们实际上如何将资源分配到其他事情上，而不仅仅是制造更多的精力来建立更多的自我。也用于在上下文中构建
讲话人（自动字幕未标注）：
of of disease and health and also for shining a light on the fact that like while we might be right here now that I do think I'll just say what maybe you were trying to say but are too humble to say that I think as long as we're looking at things just like oh this is a cancer of this tissue and not actually asking what specifically is happening to the cells there that might be common to other cancers elsewhere and
疾病和健康的问题，也为了揭示这样一个事实：虽然我们现在可能就在这里，但我确实认为我只想说你可能想说的话，但我太谦虚了，不能说我认为只要我们关注这样的事情，哦，这是这种组织的癌症，而不是真正询问那里的细胞具体发生了什么，这可能是其他地方癌症常见的情况，
讲话人（自动字幕未标注）：
like changing our nomenclature and boundaries of how we classify things opening up our minds to it >> as well as really thinking about the whole body as a like a constellation of these little microactories that is us. I am certain that people hearing this will no longer think about like metabolism just as them my metabolism but this um constellation of metabolisms and and the health status of of all the different
比如改变我们的命名法和我们对事物分类的界限，打开我们的思维>>以及真正将整个身体视为我们这些小微工厂的星座。我确信听到这个的人们将不再像我的新陈代谢一样思考新陈代谢，而是这个新陈代谢的星座以及所有不同的健康状况
讲话人（自动字幕未标注）：
cells. So, it goes without saying that it's a really unique opportunity for the general public to hear from like like a worldclass biologist working on these specific issues and related issues for decades now, right? And so, and you're a very busy person. So, I'm very grateful to to you to the University of Utah for allowing uh and encouraging public education to Howard Hughes. No, they didn't tell me to say this,
细胞。因此，不用说，对于公众来说，这是一个真正独特的机会，可以听到几十年来致力于这些具体问题和相关问题的世界级生物学家的意见，对吗？所以，你是一个非常忙碌的人。所以，我非常感谢犹他大学允许呃并鼓励霍华德休斯进行公共教育。不，他们没有让我这么说，
讲话人（自动字幕未标注）：
but I think people really need to understand what an amazing opportunity is to learn from the people and there are others in the field. you're so good at attribution who are who are really trying to figure out these really hard problems in biology that are crucial to health and to disease and therefore to curing disease and really trying to move things forward in your workshop that you call a laboratory. So you
但我认为人们确实需要了解向人们学习的绝佳机会，并且该领域还有其他人。你们非常擅长归因，他们真正试图解决生物学中的这些非常困难的问题，这些问题对健康和疾病至关重要，因此对治愈疾病至关重要，并真正试图在你们称之为实验室的工作室中推动事情向前发展。所以你
讲话人（自动字幕未标注）：
don't have to do this sort of thing but I greatly appreciate it and I speak on behalf of many many people really appreciate it. There's information and then there's superb information. So thank you so much. >> Thanks Andrew. It's been a lot of fun. >> Uh we'll do it again >> anytime. >> Cheers. >> Thank you. Thank you for joining me for today's discussion with Dr. Jared Ruer. To learn more about his work, please see
不必做这种事情，但我非常感激，我代表很多人发言，真的很感激。有信息，然后有极好的信息。非常感谢。 >> 谢谢安德鲁。这很有趣。 >> 呃，我们随时都会再做一次。 >> 干杯。 >> 谢谢。感谢您参加今天与 Jared Ruer 博士的讨论。要了解有关他的工作的更多信息，请参阅
讲话人（自动字幕未标注）：
the links in the show notes caption. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zerocost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a fivestar review. And you can now leave us comments at both Spotify and Apple. Please also
显示注释标题中的链接。如果您正在学习或喜欢此播客，请订阅我们的 YouTube 频道。这是支持我们的绝佳零成本方式。此外，请通过单击 Spotify 和 Apple 上的关注按钮来关注播客。在 Spotify 和 Apple 上，您都可以给我们留下五星级评价。您现在可以在 Spotify 和 Apple 上给我们留下评论。还请
讲话人（自动字幕未标注）：
check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comment section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's
查看今天节目开头和整个节目中提到的赞助商。这是支持这个播客的最佳方式。如果您对我有疑问，或者对播客或嘉宾有意见，或者您希望我为 Huberman Lab 播客考虑的主题，请在 YouTube 上的评论部分留言。我确实阅读了所有评论。对于那些还没有听说过的人，我即将出版一本新书。它是
讲话人（自动字幕未标注）：
my very first book. It's entitled Protocols, an operating manual for the human body. This is a book that I've been working on for more than 5 years, and that's based on more than 30 years of research and experience. And it covers protocols for everything from sleep to exercise to stress control protocols related to focus and motivation. And of course, I provide the scientific substantiation for the protocols that
我的第一本书。它的标题是《协议》，一本人体操作手册。这是我花了 5 年多时间编写的一本书，它基于 30 多年的研究和经验。它涵盖了从睡眠到锻炼，再到与注意力和动机相关的压力控制协议等各个方面的协议。当然，我为这些协议提供了科学依据
讲话人（自动字幕未标注）：
are included. The book is now available by pre-sale at protocolsbook.com. There you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols, an operating manual for the human body. And if you're not already following me on social media, I am Huberman Lab on all social media platforms. So that's Instagram, X, Threads, Facebook, and LinkedIn. And on all those
都包括在内。该书现已在 protocolbook.com 上预售。在那里您可以找到各个供应商的链接。您可以选择您最喜欢的一个。同样，这本书的名字是《Protocols》，一本人体操作手册。如果您还没有在社交媒体上关注我，我是所有社交媒体平台上的 Huberman Lab。这就是 Instagram、X、Threads、Facebook 和 LinkedIn。以及所有这些
讲话人（自动字幕未标注）：
platforms, I discuss science and science related tools, some of which overlaps with the content of the Hubberman Lab podcast, but much of which is distinct from the information on the Hubberman Lab podcast. Again, it's Huberman Lab on all social media platforms. And if you haven't already subscribed to our neural network newsletter, the neural network newsletter is a zerorost monthly newsletter that includes podcast
平台上，我讨论了科学和科学相关工具，其中一些与 Hubberman Lab 播客的内容重叠，但其中大部分与 Hubberman Lab 播客上的信息不同。同样，所有社交媒体平台上都是 Huberman Lab。如果您还没有订阅我们的神经网络时事通讯，神经网络时事通讯是 Zerorost 每月时事通讯，其中包括播客
讲话人（自动字幕未标注）：
summaries as well as what we call protocols in the form of one to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You simply go to hubbermanlab.com, go to the menu tab in the top right corner,
摘要以及我们所说的一到三页 PDF 形式的协议，涵盖了从如何优化睡眠、如何优化多巴胺、故意冷暴露等所有内容。我们有一个基本的健身方案，涵盖心血管训练和阻力训练。所有这些都是完全零成本可用的。您只需访问 hubbermanlab.com，转到右上角的菜单选项卡，
讲话人（自动字幕未标注）：
scroll down to newsletter, and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Jared Ruer. And last, but certainly not least, thank you [music] for your interest in science.
向下滚动到时事通讯，然后输入您的电子邮件。我要强调的是，我们不会与任何人分享您的电子邮件。再次感谢您参加今天与 Jared Ruer 博士的讨论。最后但并非最不重要的一点是，感谢[音乐]对科学的兴趣。
References
- 1
- 2本期官方 show notes
go.hubermanlab.com
- 3Huberman Lab 官方免责声明
hubermanlab.com
- 4犹他大学 Jared P. Rutter 官方学术主页
medicine.utah.edu
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