衰老的“万恶之源”找到了？耶鲁教授最新研究带你解锁“冻龄”的
字幕摘录
| 时间 | 英文 | 中文 |
|---|---|---|
| 0:04 | Welcome everybody. | 欢迎大家 |
| 0:05 | My name is Devin Lau. | 我叫刘德文 |
| 0:06 | I'm the associate director for Yale Center Beijing | 我是耶鲁中心北京的副局长 |
| 0:09 | and very happy to have you join us. | 很高兴你加入我们 |
| 0:13 | The center was established in 2014 | 该中心成立于2014年 |
| 0:16 | as a way for Yale to increase its engagement with China. | 作为耶鲁增加与中国交往的途径. |
| 0:21 | And we are the first and only Yale University wide center. | 我们是耶鲁大学的第一个,也是唯一的一个中心。 |
| 0:28 | So we service the whole university | 所以我们为整个大学服务 |
| 0:29 | and we like to feature people | 我们喜欢以人为特色 |
| 0:31 | from all sorts of academic fields | 来自各种学术领域 |
展开字幕全文（1181 条）
| 序号 | 英文 | 中文 |
|---|---|---|
| 1 | Welcome everybody. | 欢迎大家 |
| 2 | My name is Devin Lau. | 我叫刘德文 |
| 3 | I'm the associate director for Yale Center Beijing | 我是耶鲁中心北京的副局长 |
| 4 | and very happy to have you join us. | 很高兴你加入我们 |
| 5 | The center was established in 2014 | 该中心成立于2014年 |
| 6 | as a way for Yale to increase its engagement with China. | 作为耶鲁增加与中国交往的途径. |
| 7 | And we are the first and only Yale University wide center. | 我们是耶鲁大学的第一个,也是唯一的一个中心。 |
| 8 | So we service the whole university | 所以我们为整个大学服务 |
| 9 | and we like to feature people | 我们喜欢以人为特色 |
| 10 | from all sorts of academic fields | 来自各种学术领域 |
| 11 | to have discussions here. | 在这里进行讨论。 |
| 12 | And we've been lucky to have people from the med school | 我们很幸运有医学院的人 |
| 13 | as well as from everything from drama to art history | 从戏剧到艺术史 |
| 14 | to classical music to economics and politics. | 古典音乐 经济和政治。 |
| 15 | So a very eclectic mix of people. | 所以,一个非常精密的人组合。 |
| 16 | And we're very excited to have a talk today | 我们今天很兴奋能和你谈谈 |
| 17 | that will apply to everybody | 将适用于每个人 |
| 18 | because it's about aging and health and we're all aging. | 因为它是关于老化和健康的 我们都在老化。 |
| 19 | So we all wanna be healthy. | 所以我们都想保持健康 |
| 20 | So this is gonna be a good opportunity for us | 这对我们来说是个好机会 |
| 21 | 向大家致电 Vishwa Deepadixit教授 | |
| 22 | who is the Waldemar von Wedwitz professor of pathology, | 他是沃德玛·冯·韦德维茨 病理学教授 |
| 23 | comparative medicine and immunobiology | 比较医学和免疫生物学 |
| 24 | as well as the director of the Yale Center | 以及耶鲁中心主任 |
| 25 | for Research on Aging. | 用于老龄问题研究。 |
| 26 | He's studied veterinary medicine in India | 他在印度学兽医 |
| 27 | before completing his PhD | 在完成博士学位之前 |
| 28 | at the University of Hanover in Germany | 德国汉诺威大学 |
| 29 | as well as doing postdoc research | 以及从事博士后研究 |
| 30 | at Morehouse School of Medicine | 在莫尔豪斯医学院 |
| 31 | and the National Institute on Aging at the NIH. | 和全国老年人研究所。 |
| 32 | His lab studies immunometabolism and aging | 他的实验室研究免疫细胞瘤和衰老 |
| 33 | focusing on understanding the interactions | 侧重于了解互动 |
| 34 | between metabolic and immune systems | 代谢和免疫系统之间 |
| 35 | with the goal of revealing molecular targets | 以揭示分子目标为目标 |
| 36 | that can be harnessed to control inflammation | 可以用来控制炎症 |
| 37 | and immune dysfunction as a means to enhance health span. | 和免疫功能障碍,作为增强健康范围的手段。 |
| 38 | And so hopefully he'll explain a little bit more | 希望他能多解释一点 |
| 39 | about what exactly he's doing. | 关于他到底在做什么。 |
| 40 | And I'm sure many of us are eager to hear | 我相信我们很多人都渴望听到 |
| 41 | how we can increase our immune systems | 我们如何增加免疫系统 |
| 42 | and metabolic systems to help us increase our health span. | 和新陈代谢系统 来帮助我们扩大健康范围。 |
| 43 | 我会把事情交给Deepadixit教授 | |
| 44 | All right, thank you, Devin. | 好的 谢谢 德文 |
| 45 | Thanks for your kind introduction. | 谢谢你的介绍 |
| 46 | Let me try to share the screen. | 让我试着分享屏幕。 |
| 47 | Okay, yeah, great, great. | 好吧,是的,伟大的,伟大的。 |
| 48 | Thank you, Devin. | 谢谢你,德文 |
| 49 | And thanks to all of you, all of my colleagues. | 感谢你们所有人,我的同事们。 |
| 50 | I believe most of you are currently in China. | 我相信你们大多数现在都在中国 |
| 51 | So good morning from New Haven. | 早上好,从纽黑文。 |
| 52 | I believe it's evening for most of you. | 我想对你们来说是晚上了 |
| 53 | So it's great that we can all be connected | 所以,这是伟大的,我们都可以被连接 |
| 54 | even though it's not in person, | 虽然不是亲自的 |
| 55 | at least we are connected virtually. | 至少我们几乎是相连的。 |
| 56 | So thanks for joining. | 谢谢你的加入 |
| 57 | And like Devin mentioned, | 正如德文提到的那样, |
| 58 | my laboratory studies aging. | 我的实验室研究老化。 |
| 59 | And I'm gonna kind of give you a broad overview | 我会给你一个大致的概述 |
| 60 | of what we are doing and share some data | 分享一些数据 |
| 61 | that we have recently published. | 我们最近发表的。 |
| 62 | Okay, so I guess Devin mentioned that, | 好吧 我猜德文提到过 |
| 63 | we have quite a broad group of people, | 我们有很多人 |
| 64 | very group of audience with diverse backgrounds. | 有不同背景的观众群 |
| 65 | So I think I'm gonna try to keep the presentation | 所以,我想我会试着保持演示文稿 |
| 66 | as simple as possible. | 尽可能简单。 |
| 67 | And hopefully at the end, you can have questions | 希望最后,你可以有问题 |
| 68 | and I'll be able to answer and provide any clarifications. | 我会回答 并提供任何澄清。 |
| 69 | Okay, but just wanna remind everyone first and foremost | 好吧,但只是想提醒大家 首先 |
| 70 | is things that often get lost | 经常迷路的东西 |
| 71 | when people talk about risk, okay, risk and disease. | 当人们谈论风险, 好吧,风险和疾病。 |
| 72 | So people will say, okay, if you drink too much, | 所以人们会说,好吧,如果你喝太多, |
| 73 | if you smoke too much, | 如果你抽烟太多, |
| 74 | if you're gonna be overweight, | 如果你会超重, |
| 75 | you have much more chances of getting cancer, right? | 你有更多机会得癌症 对吧? |
| 76 | Indeed, that is the case. | 确实如此。 |
| 77 | But if you compare the risk, | 但如果你比较一下风险 |
| 78 | the relative risk of getting cancer, all type of cancers | 癌症的相对风险,各类癌症 |
| 79 | and compare these risk factors with aging, | 并将这些风险因素与老化相比较, |
| 80 | the process of aging, | 衰老的过程, |
| 81 | you find that aging by itself is strongly associated | 你发现老化本身就有着强烈的联系 |
| 82 | with increased risk of disease, okay? | 和增加的疾病风险,好吗? |
| 83 | And this risk of disease that is caused by process of aging | 而这种由衰老过程引起的疾病风险 |
| 84 | is across the board actually, okay? | 其实是全局的,好吗? |
| 85 | So for example, if you look at heart disease, | 比如说,如果你看心脏病, |
| 86 | you find almost the same thing. | 你发现几乎一样的东西。 |
| 87 | I'm sure your doctor has told you that, | 我敢肯定,你的医生已经告诉你, |
| 88 | if you have hypertension, if you're overweight again, | 如果你有高血压, 如果你再次超重, |
| 89 | smoking, you're gonna have high chances | 抽烟,你会有很高的机会 |
| 90 | of getting heart disease. | 得了心脏病 |
| 91 | But if you add aging or if you just have aging | 但如果你加了衰老 或者你只是老了 |
| 92 | as an independent risk factor, | 作为独立风险因素, |
| 93 | again, you get the same result as cancer. | 同样,你得到的结果与癌症相同。 |
| 94 | And obviously a major disease that is induced by aging, | 显然是一种由衰老引起的重大疾病, |
| 95 | a cost by aging or is a risk factor, | 由老化引起的费用或是一个风险因素, |
| 96 | where aging is a risk factor is Alzheimer's disease. | 衰老是风险因素的是老年痴呆症 |
| 97 | On the left is a graph which shows | 左边是一张显示 |
| 98 | what is the relative risk of various diseases | 各种疾病的相对风险是什么? |
| 99 | as we get older, okay? | 随着我们变老,好吗? |
| 100 | And I think it's very easy for all of you to see | 我觉得你们很容易看到 |
| 101 | what is happening here, right? | 这里发生什么了? |
| 102 | Something happens as we hit somewhere around 45, 55, right? | 当我们在45,55左右撞到某个地方时 发生了一些事情,对吧? |
| 103 | That the incidence of chronic diseases in humans | 人类慢性病的发病率 |
| 104 | increases quite dramatically from that point onwards, okay? | 从那时起就大幅增长,好吗? |
| 105 | So for these are all the diseases that are listed, | 因此,所有这些疾病 列出, |
| 106 | heart disease, cancer, stroke, emphysema, | 心脏病 癌症 中风 肺气肿 |
| 107 | pneumonia, diabetes, we also added accidents | 肺炎,糖尿病,我们还增加了意外 |
| 108 | because people fall, obviously chronic kidney diseases | 因为人们跌倒了 显然是慢性肾病 |
| 109 | and Alzheimer's. | 还有老年痴呆症 |
| 110 | So what is it, okay? | 那这是什么? |
| 111 | What is it that is caused by aging | 衰老导致的是什么 |
| 112 | or what does aging do, the process of aging do | 或者老化会怎样,老化的过程会怎样 |
| 113 | that increases the risk of all these diseases | 这些疾病的风险增加 |
| 114 | simultaneously, okay? | 同时,好吗? |
| 115 | Something must be happening. | 一定有事发生 |
| 116 | And the idea in the field is, for example, | 而这个领域的想法是,例如, |
| 117 | let's say if we develop a drug | 假设我们开发了一种药物 |
| 118 | just specifically for Alzheimer's disease, okay? | 只是针对老年痴呆症,好吗? |
| 119 | And we magically cure Alzheimer's, | 我们神奇地治愈老年痴呆症 |
| 120 | process of aging will still continue | 老龄化进程仍将继续下去 |
| 121 | and you would still get other type of diseases | 你还会得其他类型的疾病 |
| 122 | if you live long enough. | 如果你活得够长的话 |
| 123 | So in other words, people think that if, | 所以换句话说,人们会认为,如果, |
| 124 | and that's actually what's happening | 事情就是这样 |
| 125 | in the biomedical research enterprise all over the world | 全世界生物医学研究企业 |
| 126 | is that we treat each disease at a time. | 我们一次治疗每一病 |
| 127 | I know this is important and that's one of the ways | 我知道这很重要 这也是其中之一 |
| 128 | to kind of tackle these conditions. | 解决这些条件 |
| 129 | But another idea has been that instead of treating | 但另一个想法是 与其治疗 |
| 130 | each disease at a time, which are all age-linked | 每个疾病一次,都是与年龄相关的 |
| 131 | that we would eventually get, | 我们最终会得到, |
| 132 | if we treat diabetes, we'll get cancer | 如果我们治疗糖尿病,我们就会得癌症 |
| 133 | or if you treat cancer, you'll get heart disease. | 或者如果你治疗癌症,你会得心脏病。 |
| 134 | What if we can understand what is happening | 如果我们能理解发生了什么 |
| 135 | in this process of aging | 在这个老龄化过程中 |
| 136 | so that maybe we can even target those mechanisms | 这样我们甚至可以针对这些机制 |
| 137 | and delay the process of aging | 并拖延老龄化进程 |
| 138 | so that one can prevent onset of all the diseases | 防止所有疾病的爆发 |
| 139 | at the same time if we do find | 同时如果我们找到 |
| 140 | that critical mechanism of aging. | 那个衰老的关键机制 |
| 141 | So that is the big idea in the field world over | 所以,这是大 想法在世界的实地 |
| 142 | that people are quite interested in | 人们很感兴趣 |
| 143 | and my laboratory is trying to understand | 我的实验室正在试图理解 |
| 144 | what is the mechanism of the process of aging | 衰老过程的机制是什么? |
| 145 | that impacts various organs. | 影响各种器官。 |
| 146 | And our primary interest currently is an immune | 我们的主要利益是免疫 |
| 147 | and metabolic system for the reasons shown | 和新陈代谢系统的原因 |
| 148 | in the next slide. | 在下一张幻灯片中。 |
| 149 | And the slide, okay, is here. | 幻灯片就在这里 |
| 150 | So here, what you're looking at on the upper panel | 所以这里,你看到的 在上面的面板 |
| 151 | are what we call the hallmarks of aging, okay? | 我们称之为老化的标志,好吗? |
| 152 | The key mechanisms that we think are responsible | 我们认为负责的关键机制 |
| 153 | for causing process of aging itself, okay? | 导致自己衰老,好吗? |
| 154 | Among these hallmarks that are listed here, | 这些标志在这里列出, |
| 155 | inflammation is one of the major hallmarks | 炎症是主要标志之一 |
| 156 | that we are quite interested in. | 我们很感兴趣 |
| 157 | A process whereby there is increase in production | 生产增加的过程 |
| 158 | of pro-inflammatory cytokines that happens with age | 随着年龄的增长而出现的亲炎性细胞瘤 |
| 159 | in humans and in many animals. | 在人类和许多动物。 |
| 160 | There is increase in molecular damage | 分子损伤增加 |
| 161 | and the damage products accumulate in the cells | 和损害产物在细胞中积累 |
| 162 | which also cause inflammation. | 也会引起炎症。 |
| 163 | This is called as damage associated molecular patterns. | 这被称为破坏相关分子模式. |
| 164 | Then you have cellular stress, mitochondrial stress | 那你有细胞压力 线粒体压力 |
| 165 | that produces reactive oxygen species. | 产生活性氧物种。 |
| 166 | There is metabolic dysfunction that happens with age | 代谢功能障碍随着年龄而发生 |
| 167 | and visceral adiposity is one of the major hallmarks | 内脏消化是主要标志之一 |
| 168 | and risk of these factors. | 这些因素的风险。 |
| 169 | There is impaired proteostasis | 蛋白质硬化 |
| 170 | that is one of the mechanisms of aging | 这是衰老的机制之一 |
| 171 | where there is reduction in our ability | 在能力减弱的地方 |
| 172 | to clear damaged proteins, a process called autophagy. | 清理受损的蛋白质, 一个叫做自失能的过程。 |
| 173 | There's also stem cell exhaustion | 还有干细胞耗竭 |
| 174 | that our overall stem cells, either they're exhausted | 我们的整个干细胞, 要么它们筋疲力尽 |
| 175 | or they're lost or the niches where they're present | 或者是他们迷失了 或者是他们所在的地方 |
| 176 | are dysfunctional so that we are not able to regenerate | 我们无法再生 |
| 177 | things that we can do very easily when we are younger. | 我们年轻时可以轻松做的事情。 |
| 178 | And then there is genetic changes | 还有遗传改变 |
| 179 | including methylation changes in the genome | 包括基因组中的甲基化变化 |
| 180 | that alter the transcription of the genes | 改变基因的复制 |
| 181 | that control various biological process | 控制各种生物过程 |
| 182 | and then these global changes | 然后这些全球变化 |
| 183 | somehow cause this process of aging | 不知何故导致这个衰老的过程 |
| 184 | and leads to this loss of resilience. | 并导致这种复原力的丧失。 |
| 185 | But then you will ask me, | 但你会问我, |
| 186 | my grandfather is 94 years old, | 我爷爷已经94岁了 |
| 187 | he doesn't have any of these diseases, | 他没有这些疾病, |
| 188 | but my neighbor is 60 years old | 但我的邻居60岁了 |
| 189 | and he has let's say gout or heart disease. | 他可以说是痛风或心脏病 |
| 190 | So we all know that aging, | 所以我们都知道老化, |
| 191 | nobody gets all the diseases at the same time. | 没有人同时得病。 |
| 192 | So what is actually happening? | 到底发生了什么? |
| 193 | So we think that when these mechanisms are in play, | 因此,我们认为,当这些机制发挥作用时, |
| 194 | what the host does is it kind of loses its homeostasis | 宿主所做的是 它会失去它的内存 |
| 195 | or the process where all the systems are functioning | 或所有系统运行的过程 |
| 196 | at its best level. | 在最好的一级。 |
| 197 | And so there's a loss of resilience. | 故有应变之减. |
| 198 | Resilience means ability to rebound. | 复原力意味着反弹能力。 |
| 199 | But then just the loss of resilience | 但只有恢复力的丧失 |
| 200 | is not going to cause a disease. | 将不会引起疾病。 |
| 201 | So for that disease to manifest, | 所以为了证明这种疾病 |
| 202 | you have to have specific associative triggers. | 你必须有特定的关联触发器。 |
| 203 | Okay? | 好吗? |
| 204 | For example, I'll give you a very clean example, | 比如,我给你一个非常干净的例子 |
| 205 | which is disease called as gout, okay? | 那病叫痛,好吗? |
| 206 | Gout is a disease that is age related disease, | Gout是一种与年龄有关的疾病, |
| 207 | but we don't get gout. | 但我们不会被痛风。 |
| 208 | We, of course, and young people don't get gout, | 我们,当然, 年轻人不会受到痛楚, |
| 209 | old people get gout, | 老人会痛哭 |
| 210 | but gout would only happen if you have unit crystals | 但只有有单位结晶才会有痛楚 |
| 211 | that are present in the joints, okay? | 是在关节,好吗? |
| 212 | Same thing as with cancer. | 和癌症一样 |
| 213 | For cancer to manifest, | 为了显示癌症, |
| 214 | you have to have these perturbations | 你必须有这些扰动 |
| 215 | in oncogenes, in the biotics, in the background of aging. | 在肿瘤,生物, 老龄化的背景。 |
| 216 | You have to have associative trigger like dyslipidemia | 你必须要有连锁触发器,比如血滑症 |
| 217 | for heart disease to manifest. | 以显示心脏病 |
| 218 | For Alzheimer's disease, although there is still debate, | 对于阿尔茨海默症, 虽然还有争论, |
| 219 | presence of amyloid beta is considered really important | 乙酰胺的存在被认为非常重要 |
| 220 | for disease to happen. | 让疾病发生 |
| 221 | And similarly, you will only get infection and disease | 同样,你只会感染和生病 |
| 222 | with aging if you have a pathogen that is present. | 如果你有病原体的话 就会老化 |
| 223 | You have to have a virus or you have to have a bacteria | 你必须有病毒或细菌 |
| 224 | {\fn黑体\fs22\bord1\shad0\3aHBE\4aH00\fscx67\fscy66\2cHFFFFFF\3cH808080}能出现导致这种疾病 | |
| 225 | So what we are trying to understand is | 所以我们想了解的是 |
| 226 | if we can understand this process upstream here, | 如果我们能在上游了解这个过程 |
| 227 | and if we do that and we improve the ability of the host | 如果我们这样做,我们提高东道主的能力 |
| 228 | to maintain homeostasis and resilience, | * 保持适应性和复原力, |
| 229 | that in that case, we may be able to actually prevent | 那样的话,我们也许可以阻止 |
| 230 | multiple age-related diseases that occur. | 与年龄有关的多种疾病。 |
| 231 | And if you really think about it, | 如果你真的考虑一下 |
| 232 | this is really not a very new idea, okay? | 这真的不是一个非常新的想法,好吗? |
| 233 | This is a picture of Ilya Metchnikov | 这是伊利亚·梅奇尼科夫的照片 |
| 234 | who discovered macrophages or phagocytes | 发现了巨噬细胞或巨噬细胞 |
| 235 | and really laid the foundation of NAEP immune system, | 真正奠定了NAEP免疫系统的基础, |
| 236 | NAEP immunobiology. | NAEP免疫生物学. |
| 237 | He wrote this book called | 他写了这本书 |
| 238 | His Prolongation of Life Optimistic Studies | 他的人生乐观研究的长篇大论 |
| 239 | while he was in Pasteur Institute in Paris. | 他在巴黎巴斯德学院的时候 |
| 240 | If you get a chance, you should read this book, | 如果你有机会 你应该读这本书 |
| 241 | really very interesting book. | 非常有趣的书。 |
| 242 | So by the way, Ilya Metchnikov was also the person | 顺便说一句,伊利亚·梅奇尼科夫也是 |
| 243 | who coined the term gerontology, the study of aging. | 他发明了老年学这个术语 老年学的研究 |
| 244 | And Ilya Metchnikov predicted several years ago that, | 伊利亚·梅奇尼科夫几年前预言 |
| 245 | and this is the excerpt from his book, | 这是他的书的节录, |
| 246 | that he predicted that the phagocytes or macrophages | 他预言, 乳腺细胞或大phages |
| 247 | are going to be really important for the diseases of aging. | 将会对衰老的疾病非常重要 |
| 248 | And he said that the phagocytes resist the influence | 他说, 磷酸酯抵抗影响 |
| 249 | of invading poisons better than any other cells of the body | 比身体任何其他细胞都要好 |
| 250 | and sometimes are stimulated by them, okay? | 有时被他们刺激,好吗? |
| 251 | And you would be wondering, oh, what are these poisons | 你会想知道这些毒药是什么 |
| 252 | and what does he really mean? | 他到底在说什么? |
| 253 | And remember, this is what he said | 记住,这就是他说的 |
| 254 | almost 120 years ago. | 大约120年前。 |
| 255 | So at that time, we had very little knowledge | 那时我们所知甚少 |
| 256 | of modern biology and modern molecular biology. | 现代生物学和现代分子生物学。 |
| 257 | Of course, immunology was basically non-existent. | 当然,免疫学基本上不存在。 |
| 258 | So what Ilya meant with poisons is shown | 所以伊利亚对毒药的用意是 |
| 259 | in this electron micrograph image of a phagocyte | 在这个电子显微图中,一个phagocyte的图像 |
| 260 | or a macrophage that is isolated from an old animal, okay? | 或者一个与老动物隔离的巨噬体,好吗? |
| 261 | So what you see here is this phagocyte | 所以,你在这里看到的是 这个phagocyte |
| 262 | that is actually accumulating these poisons | 这其实是积累这些毒药 |
| 263 | and you will see which are the poisons. | 你将看见什么是毒药。 |
| 264 | And the poisons are pretty obvious here. | 这里的毒药很明显 |
| 265 | So this is a macrophage that has phagocytosed | 因此,这是一个宏phage 已经phago细胞化 |
| 266 | or potentially accumulated lipid in this big lipid droplet. | 或可能积累的脂质 在这个大的脂液。 |
| 267 | I mentioned that there is impaired autophagy. | 我提到有缺陷的自制性。 |
| 268 | So this is increase in protein deposits, | 这就是蛋白质矿藏的增加 |
| 269 | protein aggregates within the macrophage. | 蛋白质聚集在宏phage内部. |
| 270 | This is the nucleus of the macrophage. | 这是宏phage的核心。 |
| 271 | In this case, it is, you know, misshapen. | 在这种情况下,这是,你知道的,Misshapen。 |
| 272 | And then you can see these so-called poison-like things | 然后你可以看到这些 所谓的毒物类的东西 |
| 273 | inside these lysosomes, which are electron-dense material. | 里面是电子感应材料 |
| 274 | And then you also find these weird structures in the cell. | 然后你在牢房里也发现了这些奇怪的结构。 |
| 275 | And this is a crystal, okay? | 这是水晶,好吗? |
| 276 | These are the kind of poisons | 这些是毒药 |
| 277 | that Ilya Meshnikov was talking about. | 伊利亚・梅什尼科夫在谈论。 |
| 278 | And now we have modern words for that. | 现在我们有现代的词汇来形容它。 |
| 279 | We call them damage-associated molecular patterns, okay? | 我们称之为破坏相关分子模式,好吗? |
| 280 | And these damage-associated molecular patterns, | 这些与破坏相关的分子模式, |
| 281 | once they accumulate in cells like macrophages, | 一旦它们聚集在巨噬细胞中 |
| 282 | macrophages can actually sense them, okay? | 宏phages可以真正感觉到它们,好吗? |
| 283 | And when macrophages sense them, | 当大法师们感觉到它们时, |
| 284 | then macrophages produce inflammation. | 然后宏观phages产生炎症。 |
| 285 | And without going into too much details, | 并且没有谈太多的细节, |
| 286 | I will just summarize years of work | 我只是总结一下多年的工作 |
| 287 | that what happens with ages, | 年久失修会怎样 |
| 288 | there is a very special sensor multimolecular platform | 有一个非常特殊的传感器 多分子平台 |
| 289 | 在被称为NLRP3炎症的宏phages中, | |
| 290 | which was first discovered by Jörg Chopp in Switzerland. | 它最早由Jörg Chopp在瑞士发现. |
| 291 | This molecular pattern recognition receptor | 这种分子模式识别受体 |
| 292 | can sense many type of different poisons | 能够感知多种不同的毒药 |
| 293 | or different damage-associated molecular patterns | 或不同的与损害有关的分子形态 |
| 294 | that are listed here. | 此处列出。 |
| 295 | And that's the interesting part about this molecule, | 这就是这个分子的有趣部分 |
| 296 | because with aging, what we get is increase | 因为随着老化,我们得到的就是增加 |
| 297 | of multiple type of damage-associated molecular patterns | 多种类型与损害有关的分子形态 |
| 298 | or these poisons, okay? | 或者这些毒药,好吗? |
| 299 | And inflammasome can get activated by many of these things. | 而炎症可以被很多这些东西激活. |
| 300 | Now you would ask, oh, well, if that is the case, | 现在你会问,哦,嗯,如果是这样的话, |
| 301 | why would biology have, | 为什么生物学会 |
| 302 | or why would we even have this molecule? | 或者我们为什么要拥有这个分子? |
| 303 | Obviously we don't wanna get disease all the time. | 显然我们不想老是生病 |
| 304 | No, actually this molecule is present | 不,实际上这个分子存在 |
| 305 | to protect us from infections. | 保护我们免受感染。 |
| 306 | However, in the process of aging, | 然而,在老龄化过程中, |
| 307 | what we get is this continuous slow cellular damage | 我们得到的是这种持续缓慢的细胞损伤 |
| 308 | and macrophages try to clear it by activating this complex, | 和宏phages试图通过激活 这个复杂, |
| 309 | but the damage kind of continues | 但破坏的种类继续 |
| 310 | because process of aging time continues. | 因为老化的过程还在继续 |
| 311 | And what it does is, | 而它所做的是, |
| 312 | is basically continuously activates this complex. | 基本上就是不断激活这个复合体 |
| 313 | And when this complex is continually activated, | 当这个综合体不断被激活时, |
| 314 | what it does is it cleaves this important enzyme | 它所做的就是把这个重要的酶切开 |
| 315 | 称为CasPase-1。 | |
| 316 | 然后CasPase-1启动 | |
| 317 | two very critical cytokines, IL-18 and IL-1 beta. | 两个非常关键的细胞基,IL-18和IL-1β. |
| 318 | And these two cytokines then produce inflammation. | 而这两个细胞基随后产生炎症. |
| 319 | And when we block these NLRP3 inflammasome genetically, | 当我们封锁这些 NLRP3 的炎症 遗传, |
| 320 | then you can actually prevent the process of inflammation, | 然后你可以防止炎症的发生 |
| 321 | at least in mice. | 至少在老鼠身上是这样 |
| 322 | And once we do that, | 一旦我们这样做, |
| 323 | what you also get is inhibition | 你得到的也是抑制 |
| 324 | or protection of animals from many diseases. | 或保护动物免受许多疾病的侵害。 |
| 325 | So the animals, the mice that are old | 所以动物, 老鼠老了 |
| 326 | and have reduced activity of NLRP3 inflammasome | 并减少了NLRP3炎症的活性 |
| 327 | are protected from bone loss. | 避免骨折。 |
| 328 | They are also protected from diabetes | 她们还受到糖尿病的保护 |
| 329 | and they have improved immune system | 它们改善了免疫系统 |
| 330 | because they have better thymic function. | 因为他们有更好的胸腔功能。 |
| 331 | They also have greater memory in old age | 老人的记忆力也比较强 |
| 332 | because they have less cognitive decline | 因为他们的认知下降较少 |
| 333 | and less inflammation in the brain. | 少点脑部炎症 |
| 334 | And they are less frail. | 而且它们也比较弱。 |
| 335 | And then you would wonder, wow, | 然后你会想,哇, |
| 336 | this is like sounds pretty interesting. | 这听起来很有趣 |
| 337 | How come there are effects on so many different things? | 怎么会有这么多不同的东西? |
| 338 | And I think the answer is truly what Meshnikov had predicted | 我认为答案是梅什尼科夫预言的 |
| 339 | is it's the phagocytes. | 是法甲细胞 |
| 340 | So macrophages are present in all these different locations, | 因此,宏phages 存在于所有这些不同的地点, |
| 341 | as tissue resident cells. | 作为组织内细胞。 |
| 342 | And I think what is happening with aging | 我觉得老掉牙了 |
| 343 | is that these cells are getting activated | 这些细胞被激活了 |
| 344 | through the process of this molecule | 通过这个分子的过程 |
| 345 | called as NLRP3 inflammasome. | 被称为 NLRP3 炎症。 |
| 346 | So one of the things we are interested in | 所以,我们感兴趣的一件事 |
| 347 | is to find where does inflammation originate. | 是要找出炎症发源地 |
| 348 | What is the source of inflammation? | 发炎之源何在? |
| 349 | Organ source and also the cellular source. | 器官来源和细胞来源 |
| 350 | So what you're looking here is a CT scan | 你在这里看到的是CT扫描 |
| 351 | of a healthy person and 31 year old. | 一个健康的人 和31岁。 |
| 352 | And actually also a healthy person that is 74 year old. | 其实也是个74岁的健康人。 |
| 353 | There is no, both these people | 没有,这两个人 |
| 354 | have the same amount of weight, okay? | 体重相同,好吗? |
| 355 | But there is one big difference. | 但有一个很大的区别。 |
| 356 | I think you can see it very clearly in this image, right? | 我想你能从这个图像中看得很清楚,对吧? |
| 357 | You see the difference? | 你看到区别了吗? |
| 358 | Yep. | 对 |
| 359 | So the older people, as we get older, | 因此,老年人,随着我们变老, |
| 360 | we accumulate fat, okay? | 我们积累脂肪,好吗? |
| 361 | We accumulate fat inside our viscera | 我们的内脏里积聚脂肪 |
| 362 | or wherever organs are. | 或器官所在的地方。 |
| 363 | It(学名:Niceral adiposity)为pos科pos属下的一个种. | |
| 364 | You don't have to be actually obese to accumulate it. | 你不必真的肥胖来积累它。 |
| 365 | You know, obviously once there is obesity and overweight, | 你知道,很明显 一旦有肥胖和超重, |
| 366 | you would accumulate fat inside your stomach. | 你会在胃里积累脂肪 |
| 367 | However, even if you maintain a normal body weight, | 然而,即使你保持正常的体重, |
| 368 | you would still accumulate fat inside your organs | 你会在你的器官里积累脂肪 |
| 369 | called visceral adiposity, okay? | 叫做内脏消化,好吗? |
| 370 | And it is known now that increase of fat, | 现在人们知道脂肪的增加, |
| 371 | both in men and in women with age, | 不论男女, |
| 372 | as shown here, is a major risk factor | 如本文所示,这是一个主要风险因素 |
| 373 | for several diseases that emerge with age. | 对于随着年龄而出现的几种疾病。 |
| 374 | And what we're trying to understand is, | 而我们试图理解的是, |
| 375 | is it possible that increase of this visceral fat | 这种粘膜脂肪的增殖 有可能吗 |
| 376 | is causing inflammation with age? | 会不会因为年龄而发炎? |
| 377 | And is that the part of the mechanism | 这是机制的一部分 |
| 378 | of process of aging itself? | 衰老过程本身? |
| 379 | And okay, so this is a slide | 好吧,这是一张幻灯片 |
| 380 | which is very interesting in my view | 我觉得这很有趣 |
| 381 | because what you're looking at here | 因为你在看什么 |
| 382 | is everything that is green is a myeloid cell, | 绿色的一切都是个小细胞, |
| 383 | which is mostly in this case are macrophages | 这其中大多是宏phages |
| 384 | and a few neutrophils. | 还有几颗神经素 |
| 385 | And if you would show this figure to any pathologist | 如果你能向任何病理学家展示这个数字 |
| 386 | and ask, what is this? | 问,这是什么? |
| 387 | They will say, oh, this is an immune organ | 他们会说 这是免疫器官 |
| 388 | because everything that's green is a myeloid cell | 因为所有绿色的东西都是小细胞 |
| 389 | and myeloid cells are immune cells | 蛋白质细胞是免疫细胞 |
| 390 | and there are so many green cells, | 还有这么多的绿色细胞, |
| 391 | so it would be an immune organ. | 所以它会是一个免疫器官。 |
| 392 | But the answer is it's not an immune organ. | 但答案是它不是一个免疫器官. |
| 393 | It's actually adipose tissue. | 它实际上是脂肪组织. |
| 394 | Your fat tissue. | 你的脂肪组织。 |
| 395 | And what is quite interesting is that the fat tissue | 有趣的是脂肪组织 |
| 396 | in normal situation, in healthy situation | 在正常情况下,在健康情况下 |
| 397 | actually harbors lots of these macrophages | 其实藏了很多这些宏phages |
| 398 | that are present in the fat. | 存在于脂肪中。 |
| 399 | And what these macrophages do is they control, | 而这些巨型动物所做的就是控制 |
| 400 | they maintain the normal function of the adipose tissue. | 它们保持脂肪组织的正常功能. |
| 401 | And we're trying to understand with age, | 我们试图理解年龄, |
| 402 | as aging happens, what happens to this organ | 随着衰老的发生,这个器官会发生什么 |
| 403 | which increases with age? | 哪个随着年龄的增长? |
| 404 | Are there changes in the immune system? | 免疫系统有变化吗? |
| 405 | And are these immune cells aberrantly activated | 这些免疫细胞异常激活 |
| 406 | to cause increased inflammation? | 导致炎症增加? |
| 407 | So here is some data to prove to you | 所以这里有一些数据可以证明给你 |
| 408 | that indeed adipose tissue is an immunological organ. | 脂肪组织确实是一种免疫器官。 |
| 409 | So you're looking at single cell sequencing analysis here | 所以这里是单细胞测序分析 |
| 410 | of young visceral fat from a healthy mouse | 健康鼠标的幼体脂肪 |
| 411 | and old visceral fat from an aged animal. | 和来自老年动物的老脂肪 |
| 412 | And when you do the single cell analysis | 当你做单细胞分析时 |
| 413 | 看看这些U -maps, | |
| 414 | this work was done by my former colleague, | 这项工作是我前同事完成的, |
| 415 | Emily Goldberg,她现在是教师 | |
| 416 | in University of California, San Francisco. | 就读于加州大学旧金山分校. |
| 417 | So what Emily found was that in young animals, | Emily发现在幼兽身上 |
| 418 | there are lots of different type of immune cells | 很多种类不同的免疫细胞 |
| 419 | that are present within the adipose tissue. | 存在于脂肪组织内 |
| 420 | So this is, for example, | 所以,举例来说, |
| 421 | cluster of very specific, very interesting cell | 一组非常具体、非常有趣的单元格 |
| 422 | called as innate lymphocyte cell two. | 被称为先天淋巴细胞2 |
| 423 | 这里有宏phages。 | |
| 424 | 宏phages有不同类型. | |
| 425 | 有NKT细胞. | |
| 426 | There are gamma delta T cells. | 有伽玛三角洲T细胞. |
| 427 | There are T cells. | 有T细胞 |
| 428 | There are B cells. | 有B细胞. |
| 429 | Every type of immune cell that you know of is present | 你所知道的每一种免疫细胞都存在 |
| 430 | except neutrophils and eosinophils, okay? | 除了中营养素和迷幻药,好吗? |
| 431 | But what happens with age is very dramatic. | 但随着年龄的增长 却非常戏剧化 |
| 432 | So some cells are actually completely lost. | 因此一些细胞实际上完全丢失. |
| 433 | So for example, if you look at the cells called as ILC2s, | 举例来说,如果你看看所谓的ILC2的细胞, |
| 434 | they actually disappear. | 他们实际上消失了。 |
| 435 | Several other cells also will lose with age, | 其他几个细胞也会随着年龄的增长而失去 |
| 436 | for example, NKT cells. | 例如NKT细胞. |
| 437 | And macrophages that I've been telling you about, | 和宏观phages,我已经告诉你, |
| 438 | in fact, also go down, okay? | 事实上,也要下去,好吗? |
| 439 | Remember, Mechnikov had told us 100 years ago | 记住,梅奇尼科夫100年前告诉我们的 |
| 440 | that phagocytes help clear the poisons from the body, okay? | 那个法甲细胞有助于清除 体内的毒药,好吗? |
| 441 | Help clear the debris. | 帮助清除残骸。 |
| 442 | And it seems that we are losing those cells | 似乎我们失去了这些细胞 |
| 443 | that are helpful to us with age. | 对我们年长有帮助 |
| 444 | And this leads us to definition | 这让我们有了定义 |
| 445 | of what are the cellular hallmarks of immunological aging. | 免疫衰老的细胞特征是什么 |
| 446 | What happens to the immune system with aging, okay? | 衰老后免疫系统会怎样,好吗? |
| 447 | And those are, few of those are listed here. | 这些是,这里列出的很少。 |
| 448 | One is that we and others have shown that, | 一是我们和其他人已经表明, |
| 449 | in fact, the T cells expand with age, | 事实上,T细胞随着年龄的增长而扩大, |
| 450 | including the suppressor cells or the T regulatory cells. | 包括抑制细胞或T调节细胞。 |
| 451 | They also increase. | 它们也有所增加。 |
| 452 | There is expansion of a specific type of B cells | 某类B细胞在扩张 |
| 453 | called as a pro-inflammatory aged B cells. | 被称为亲炎的B细胞。 |
| 454 | And this happens in unique structures | 这发生在独特的结构中 |
| 455 | called as fat-associated lymphoid clusters. | 称为脂肪相关淋巴结。 |
| 456 | This happens in the adipose tissue. | 这发生在脂肪组织中. |
| 457 | There is a loss of natural killer cells | 自然杀手细胞的减少 |
| 458 | and the natural killer T cells. | 自然杀手T细胞 |
| 459 | And there is a loss of innate lymphocyte cells to ILC2s. | 而原生淋巴细胞则会失去ILC2. |
| 460 | And there is also a reduction | 也有一个减少 |
| 461 | of a specific type of dendritic cell subset | 特定类型的凹槽子集 |
| 462 | 和顺位静脉 宏观或phagocytes,好吗? | |
| 463 | So the question is, when all these things are happening, | 所以问题是 当这一切发生时 |
| 464 | what can we, how can we actually study | 我们能怎样,怎样才能真正学习 |
| 465 | if we can block those things, | 如果我们能阻止那些东西, |
| 466 | if we can block the inflammation? | 如果我们能阻止炎症发生? |
| 467 | And the one of the things that I have been interested in | 我感兴趣的一件事 |
| 468 | for several years in my lab is this process | 在我实验室里待了几年就是这个过程 |
| 469 | where there is negative energy balance in a host. | 在宿主能量平衡为负值的地方 |
| 470 | In other words, when you eat less, okay? | 换句话说,当你少吃,好吗? |
| 471 | When energy consumed, which is, | 当能量消耗,也就是, |
| 472 | this is basically your food, okay? | 这基本上是你的食物,好吗? |
| 473 | You get energy by consuming food. | 你通过消费食物获得能量. |
| 474 | If you consume less food and you expend more energy, | 如果你消耗的食物少 花费更多的能量, |
| 475 | so in other words, if you're eating less, | 所以换句话说,如果你少吃一点 |
| 476 | walking more, running more, | 走得更远 跑得更远 |
| 477 | this would cause your energy balance equation | 这会导致你的能量平衡方程式 |
| 478 | to be in negative, which means that you need more energy | 表示你需要更多的能量 |
| 479 | but you're consuming less of it. | 但你消费更少。 |
| 480 | When this happens, okay? | 当这种情况发生时,好吗? |
| 481 | What you actually get is increased lifespan, okay? | 你实际上得到的是延长寿命,好吗? |
| 482 | This has been shown in many, many species | 许多物种都表现出来 |
| 483 | and through a process called as caloric restriction. | 并且通过一个叫做卡路里限制的过程。 |
| 484 | If you restrict calories, mice, rats live longer, | 如果你限制热量,老鼠,老鼠活得更长, |
| 485 | flies, worms live longer, there is some indication | 苍蝇,蠕虫活得更长,有迹象表明 |
| 486 | that even monkeys may live longer. | 即使是猴子也会活得更长 |
| 487 | But one of the things that you have to imagine | 但其中一件事,你必须想象 |
| 488 | when a host is in negative energy balance, | 当一个宿主出现负能量平衡的时候, |
| 489 | it has to do many things, right? | 它必须做很多事情,对不对? |
| 490 | It has now be able to judiciously use the remainder | 它现在能够明智地使用其余部分 |
| 491 | of the fuel it has, these are all energetic substrates. | 这些都是能量的底物 |
| 492 | So immune system and metabolic system | 所以免疫系统和代谢系统 |
| 493 | have to have this coordinated dance | 一定要有这种协调的舞蹈 |
| 494 | so that it can maintain homeostasis. | 这样它就可以保持优雅 |
| 495 | There is one problem, however, okay? | 但有一个问题,好吗? |
| 496 | When you get increased lifespan by restricting calories, | 当你通过限制卡路里来延长寿命时 |
| 497 | the problem is of trade-offs, okay? | 问题是权衡,好吗? |
| 498 | So there are trade-offs with this increased lifespan | 寿命的延长有取舍 |
| 499 | so that you have reduction in growth. | 以便你减少增长。 |
| 500 | Your reproductive system is less active, | 你的生殖系统不太活跃 |
| 501 | immune system is less active. | 免疫系统不活跃。 |
| 502 | So basically, in other words, | 所以基本上,换句话说, |
| 503 | energy is diverted from less essential functions | 能源从不太重要的功能中转移 |
| 504 | to more essential functions, | 履行更重要的职能, |
| 505 | which is like running the heart, running the brain. | 这就像运行心脏,运行大脑。 |
| 506 | And people think that the longevity that you get | 人们觉得你长寿 |
| 507 | because of caloric restriction | 由于卡路里的限制 |
| 508 | is because of these cellular trade-offs, okay? | 是因为这些细胞的权衡,好吗? |
| 509 | Also, organismal trade-offs. | 还有 有机的权衡 |
| 510 | Now you would ask, okay, | 现在你会问,好吧, |
| 511 | if we are going to have a trade-off, | 如果我们要有一个权衡, |
| 512 | if we're gonna live longer, but if we cannot grow, | 如果我们要活更长, 但如果我们无法成长, |
| 513 | and if reproduction is bad, we are getting infections, | 如果生殖不良 我们就会感染 |
| 514 | what's the point of living? | 何等为众生. |
| 515 | I fully agree with you, you know? | 我完全同意你,你知道吗? |
| 516 | So the question is, how do we study this mechanism | 所以问题是,我们如何研究这个机制 |
| 517 | in a way where there is no trade-off, | 在没有权衡的情况下, |
| 518 | but we can understand what is driving these positive effects? | 但我们能理解是什么驱使这些积极效应? |
| 519 | So, and then, you know, it is known, | 所以,然后,你知道,这是众所周知的, |
| 520 | like I told you, that calorie restriction increases lifespan. | 我说过,卡路里限制会延长寿命 |
| 521 | But then there was a paper | 但后来有一篇论文 |
| 522 | that showed that several mouse strains | 显示多个鼠标菌株 |
| 523 | actually not only live not longer, | 其实不仅活得不长 |
| 524 | they actually live shorter, okay? | 他们活得更短,好吗? |
| 525 | So some mouse strains live longer, some live shorter. | 所以有些老鼠菌株活得更久,有些则活得更短. |
| 526 | There was a big debate, and everybody got really confused | 一场大辩论,大家都很困惑 |
| 527 | whether calorie restriction is really real, | 卡路里限制是否是真的 |
| 528 | or whether it is just some sort of an artifact | 还是只是某种文物 |
| 529 | of a laboratory condition, | 实验室状况, |
| 530 | because we know that the animals, | 因为我们知道动物, |
| 531 | when they are housed in animal houses, | 当他们住在牲畜的家中的时候, |
| 532 | they're in a very different condition | 他们的处境完全不同 |
| 533 | as compared to what we live, | 与我们所生活的一切相比, |
| 534 | because the animals live in a pathogen-free environment. | 因为动物生活在一个没有病原体的环境中。 |
| 535 | They don't see any pathogens. | 他们看不到任何病原体。 |
| 536 | And, you know, if you take a mouse or a worm or a fly | 而且,你知道,如果你拿一只老鼠,一只虫或一只苍蝇 |
| 537 | and stop giving it, you know, it's 40% of the food, | 停止给它,你知道, 这是40%的食物, |
| 538 | animal does not know what is happening, | 动物不知道发生了什么, |
| 539 | because animal does not sign consent forms. | 因为动物不会签署同意书 |
| 540 | So animal undergoes the stress response. | 所以动物会承受压力 |
| 541 | So a lot of these things then cause changes in the physiology | 因此,很多这些东西 然后引起生理变化 |
| 542 | so that it is very difficult to understand | 所以很难理解 |
| 543 | what is actually happening during calorie restriction. | 在卡路里限制期间究竟发生了什么 |
| 544 | So the idea was to actually do studies in human beings, okay? | 所以这个想法是真正做 人类的研究,好吗? |
| 545 | Do a calorie restriction study in humans. | 对人类进行卡路里限制研究. |
| 546 | And then if we find that calorie restriction in humans | 如果我们发现卡路里在人类中的限制 |
| 547 | is biologically relevant, | 与生物学相关, |
| 548 | then we identify endogenous targets | 然后我们找出内在目标 |
| 549 | that are affected by CR, | 受CR影响, |
| 550 | and then use those targets to assign causality, | 然后利用这些目标来指定因果关系, |
| 551 | to see whether they're just, you know, | 看看他们是否只是,你知道, |
| 552 | really, if they're passengers or if they're drivers, | 真的,如果他们是乘客或司机, |
| 553 | if they're important, | 如果它们是重要的, |
| 554 | then we can test causality using model organisms | 然后我们就可以用模型生物测试因果关系 |
| 555 | and see whether they're important for mechanisms of disease | 看看它们是否对疾病机理很重要 |
| 556 | or lifespan itself. | 或寿命本身。 |
| 557 | And this is what we did. | 这就是我们所做的。 |
| 558 | So this was a study called a Scalery. | 所以,这是一个研究,叫做"天平"。 |
| 559 | It was a clinical trial | 这是临床试验 |
| 560 | that was done at three different sites at Baton Rouge. | 在巴吞鲁日的三个不同地点完成的 |
| 561 | This is my former institution. | 这是我的前机构。 |
| 562 | I used to work here before I came to Yale, | 我到耶鲁大学之前就在这里工作过 |
| 563 | in St. Louis and Washington University, | 在圣路易斯和华盛顿大学, |
| 564 | in Boston and Tufts University. | 在波士顿和塔夫茨大学 |
| 565 | And what the study wanted to do was basically | 而研究想要做的 基本上是 |
| 566 | take people that are healthy | 带健康的人 |
| 567 | between 25 and 45 years of age. | 25至45岁。 |
| 568 | They're not old people. | 他们不是老人。 |
| 569 | And restrict the calorie intake of the individuals by 25%. | 并且将个人的卡路里摄入量限制25%. |
| 570 | So you eat 25% less food for two years, okay? | 所以,你吃25% 少的食物两年,好吗? |
| 571 | And then after two years or during that time, | 过了两年或在这期间 |
| 572 | study whether calorie restriction | 研究是否限制卡路里 |
| 573 | or negative energy balance is reducing the risk of disease. | 或负能量平衡正在减少疾病风险。 |
| 574 | And here is the data. | 这是数据。 |
| 575 | Remember, the clinical trial wanted to restrict people | 记住,临床试验是为了限制人 |
| 576 | by about 25%. | 大约25%。 |
| 577 | But in fact, when you take people | 但事实上,当你带人 |
| 578 | and you tell them to restrict calories | 你告诉他们限制卡路里 |
| 579 | and tell them to go about their life as normal | 让他们过正常的生活 |
| 580 | in free living condition, | 自由生活, |
| 581 | human beings, it seems, | 人类,似乎, |
| 582 | can only restrict about 15% calories, not 25%. | 只能限制约15%的热量,而不是25%。 |
| 583 | And this is the percent of calorie restriction in people. | 这就是卡路里在人群中限制的比例。 |
| 584 | This is baseline, which means at this time of the study, | 这是基线,这意味着在研究的此时此刻, |
| 585 | M12 means 12 months after the study | M12意味着在研究后12个月 |
| 586 | and 24 months, so year one and year two. | 24个月,所以第一年和第二年。 |
| 587 | And what the study initially showed | 最初的研究显示 |
| 588 | were there were some markers of aging | 是否有一些老化标记 |
| 589 | and oxidative damage which were reduced | 减少的氧化损害 |
| 590 | when people underwent calorie restriction. | 当人们受到卡路里的限制。 |
| 591 | So which was quite exciting | 所以,这是相当令人兴奋的 |
| 592 | and suggesting that there may be indeed be | 并暗示也许确实有 |
| 593 | that calorie restriction may be beneficial to people. | 限制卡路里对人们有好处 |
| 594 | And then the question was to what should we study | 然后问题是我们该研究什么 |
| 595 | that actually tells us | 这其实告诉我们 |
| 596 | that there is effect of calorie restriction | 有卡路里限制的效果 |
| 597 | because remember I told you | 因为我告诉过你 |
| 598 | that these are all healthy people, okay? | 这些人都是健康的,好吗? |
| 599 | I also told you they are not old people. | 我也说过他们不是老人 |
| 600 | So if somebody is old and is young and healthy, | 所以如果有人年老 年轻健康 |
| 601 | what are you going to study that is gonna tell you | 你要学习什么? |
| 602 | that something is working? | 东西起作用了吗? |
| 603 | Okay, luckily for us, for immunologists, | 好吧,幸运的是为我们, 对于免疫学家, |
| 604 | there is organ that ages faster | 有器官会变老更快 |
| 605 | than any other organ of the body | 而不是该机构的任何其他机关 |
| 606 | and this organ is called as the thymus. | 这器官被称为胸腺 |
| 607 | And the thymus is a key organ, as you know, | 胸腺是关键器官 如你所知 |
| 608 | that produces T cells and what you're looking | 产生T细胞 和你正在寻找的东西 |
| 609 | at the magnetic resonance imaging | 在磁共振成像时 |
| 610 | of a healthy 25 year old person | 健康25岁的人 |
| 611 | and a 45 year old person on the right. | 右边还有个45岁的老人 |
| 612 | And if you do the MRI, this is the heart, | 如果你做核磁共振,这是心脏, |
| 613 | it's the aorta, this is the sternum | 这是主动脉 这是胸骨 |
| 614 | and this area here is the thymus, okay? | 这个区域是胸腺,好吗? |
| 615 | And this white spot where my arrow is | 我箭头所在的白点 |
| 616 | is the fat inside the thymus, okay? | 胸腺里面的脂肪,好吗? |
| 617 | Let me find it for you again, this right here. | 让我再给你找一次,这里 |
| 618 | However, if you look at somebody | 不过,如果你看一个人 |
| 619 | who is just 45 years of age and healthy, | 年仅45岁 身体健康 |
| 620 | you can see that all the thymus is white. | 你可以看到所有的胸腺都是白色的 |
| 621 | So this is the heart, is the sternum. | 这是心脏,是胸骨。 |
| 622 | So the 45 year old person, about 80% of the thymus | 所以45岁的人,大约80%的胸腺 |
| 623 | is all made up of fat, yes, in healthy people. | 在健康人群中都是由脂肪组成的 |
| 624 | And it's highly conserved | 保护得很好 |
| 625 | throughout evolution and vertebrates. | 整个进化和脊椎动物。 |
| 626 | This is the same image of this person. | 这个人也是这样 |
| 627 | Here we have basically blocked the signal | 我们基本上封锁了信号 |
| 628 | that is coming from fat. | 这是来自脂肪。 |
| 629 | So the only signal that is coming from is water. | 所以,唯一的信号是水。 |
| 630 | So with that, you can actually calculate | 因此,你可以计算 |
| 631 | the functional volume of the thymus. | 胸腺的功能体积。 |
| 632 | So this is the thymus in a 25 year old person, | 这是25岁老人的胸腺 |
| 633 | you can clearly see it is present. | 你可以看到它的存在。 |
| 634 | And in a 45 year old person, | 而在一个45岁的人, |
| 635 | there is nothing or almost nothing. | 什么也没有,几乎什么都没有。 |
| 636 | So we wanted to study what does calorie restriction | 所以我们想研究什么是卡路里限制 |
| 637 | do to the thymus. | 对胸腺做点什么 |
| 638 | And the effects were really very striking. | 效果非常惊人。 |
| 639 | And this work was done by my colleague, Dr. Yuni Yun, | 这项工作是由我的同事尤尼·云博士完成的, |
| 640 | who's an associate research scientist in the lab. | 他是实验室的助理研究科学家 |
| 641 | And what she found was that when you study people | 而她发现 当你学习人 |
| 642 | at the baseline, | 在基线, |
| 643 | and then after two years of calorie restriction, | 经过两年的卡路里限制, |
| 644 | you see that overall people have lost some weight. | 你看,整体上的人 已经失去了一些体重。 |
| 645 | This is why it is all weight, basically fat. | 这就是为什么它都是重量,基本上脂肪。 |
| 646 | But if you look at the thymus, | 但是如果你看着胸腺 |
| 647 | so this is the same person that came at baseline | 因此,这是同一个人 来到基线 |
| 648 | and after two years. | 两年后 |
| 649 | And when you look at this, | 当你看到这个时 |
| 650 | actually the size of the functional thymus | 实际功能胸腺的大小 |
| 651 | is actually bigger. | 其实是更大的。 |
| 652 | So somehow calorie restriction in human beings | 所以,不知何故卡路里限制 人类 |
| 653 | is in fact rejuvenating the function of the thymus, | 实际上是在恢复胸腺的功能, |
| 654 | increasing the function of the thymus, | 增加胸腺的功能, |
| 655 | not just protecting, but actually rejuvenating, reversing, | 不仅保护,而且实际上 振兴,逆转, |
| 656 | which was quite surprising | 这很令人惊讶 |
| 657 | because we did not really expect this to happen. | 因为我们没有真正预期到会发生这种情况。 |
| 658 | So this is just the quantification of the thymic volume, | 所以这只是对胸腔体积的量化 |
| 659 | the functional thymic volume. | 功能性胸腔音量。 |
| 660 | There is a marker that can tell us about new T cells | 有一个标记可以告诉我们新的T细胞 |
| 661 | that are made by thymus, | 是用胸腺造出来的, |
| 662 | just because the size of the thymus is bigger | 只是因为胸腺的大小更大 |
| 663 | doesn't mean the thymus is better. | 这并不意味着胸腺更好 |
| 664 | So you have to measure whether the thymus | 所以,你必须衡量 胸腺 |
| 665 | is making new T cells. | 正在制作新的 T 单元格。 |
| 666 | So there's an episomal DNA, | 所以有间质DNA |
| 667 | which we can measure in T cells | 我们可以在 T 单元格中测量 |
| 668 | that indicates presence of new T cells. | 表示存在新的 T 单元格。 |
| 669 | So you can see that when people come at baseline, | 你可以看到当人们来到基线, |
| 670 | but after two years of CR, | 但过了两年CR, |
| 671 | they all have increased in this marker. | 他们都增加了这个标记。 |
| 672 | So in the next few minutes, | 所以在接下来的几分钟里 |
| 673 | I will quickly show you the data | 我会很快把数据给你看 |
| 674 | and not go over all the details, | 而不详谈一切细节, |
| 675 | but give you some big picture of what we're trying to do. | 但是,给你一些大 图片我们想做什么。 |
| 676 | So obviously we're trying to understand | 很明显我们想了解 |
| 677 | how does calorie restriction works? | 卡路里的限制怎么用? |
| 678 | What is the mechanism in this case for reducing inflammation? | 在这种情况下,减少炎症的机制是什么? |
| 679 | And then if we find that mechanism, | 然后,如果我们找到这个机制, |
| 680 | can we actually use those targets | 我们能否真正使用那些目标 |
| 681 | to then develop maybe new drugs against inflammation | 然后再研制新的抗炎药物 |
| 682 | and potentially against aging? | 和潜在的反对老化? |
| 683 | So we collected the adipose tissue from people at baseline | 我们从基线人群那里收集脂肪组织 |
| 684 | after one year of calorie restriction | 经过一年的卡路里限制 |
| 685 | and after two years of calorie restriction | 并经过两年的卡路里限制 |
| 686 | and did the transcriptomics analysis. | 并做了笔录分析。 |
| 687 | And what is really striking is the differences | 真正令人惊讶的是差异 |
| 688 | that exist in people after calorie restriction. | 存在于卡路里限制后的人中 |
| 689 | So these are the genes that are inhibited. | 因此这些是被抑制的基因. |
| 690 | So you can see that people have a dramatically | 所以,你可以看到,人们有一个戏剧性 |
| 691 | homogeneous response in this case to this intervention. | 在本案中,对这一干预的一致反应。 |
| 692 | Several genes that are up and down. | 数种上下基因. |
| 693 | And these are the pathways that are really interesting | 这些是真正有趣的途径 |
| 694 | that are changed in human beings. | 人类已经改变 |
| 695 | So these are pathways that are increased | 所以这些是增加的路径 |
| 696 | by calorie restriction in human beings. | 通过卡路里限制人类。 |
| 697 | We think that these pathways may even be important | 我们认为这些途径甚至可能很重要 |
| 698 | for lifespan itself, maybe increasing the lifespan, | 对寿命本身,也许增加寿命, |
| 699 | because some of them have previously been shown in worms | 因为其中一些以前在蠕虫体内显示过 |
| 700 | to be associated with increased lifespan. | 与延长寿命有关。 |
| 701 | And then there are pathways that are reduced. | 后有道减. |
| 702 | And the pathways that are reduced | 和减少的路径 |
| 703 | are mostly in the pathways that are in inflammation. | 大多在炎症发作的道路上。 |
| 704 | And one of the genes that we discovered | 我们发现的基因之一 |
| 705 | to be really interesting in this case is this protein, | 真正有趣的是这个蛋白质, |
| 706 | this gene called as PLA2G7, | 这个基因叫做PLA2G7 |
| 707 | which is inhibited by calorie restriction. | 受到卡路里限制的限制 |
| 708 | This is a very interesting molecule | 这是一个非常有趣的分子 |
| 709 | which controls the lipoprotein homeostasis. | 控制了脂蛋白的顺势管 |
| 710 | It is mostly produced by the macrophages | 大部分是由巨型动物产生的 |
| 711 | and controls hydrolysis of platelet activating factor. | 控制板块激活因子的水解。 |
| 712 | So this protein is, or this gene and protein | 所以这个蛋白质是, 或者这个基因和蛋白质 |
| 713 | is present in very high amounts also in the blocks | 以非常高的数量出现在区块中 |
| 714 | in the heart disease. | 在心脏病。 |
| 715 | And there have been some studies previously showing | 以前的一些研究显示 |
| 716 | that if you reduce PLA2G7, | 如果你减少PLA2G7, |
| 717 | it can reduce some inflammation. | 它可以减少一些炎症。 |
| 718 | So we were very interested to see whether PLA2G7 | 所以我们很想知道PLA2G7是不是 |
| 719 | is one of the molecules that is inhibited by CR, | 是受CR抑制的分子之一, |
| 720 | but maybe a target for potentially reducing inflammation. | 但或许是减少炎症的目标 |
| 721 | So what we did was we created the mice that lack PLA2G7. | 所以,我们做的就是创造了那些缺乏PLA2G7的老鼠. |
| 722 | So these mice are more or less normal here, | 所以这些老鼠在这里或多或少是正常的, |
| 723 | wild type and knockouts. | 狂野类型和击倒。 |
| 724 | But if you give the wild type animals in black, | 但如果你给野生动物 黑衣, |
| 725 | the diet, a high fat diet, | 饮食,高脂肪的饮食, |
| 726 | or what we call the Western diet, | 或者我们所谓的西方饮食, |
| 727 | you see that there is an increase in body weight. | 你看,体重有增加。 |
| 728 | There is mice become fat, | 有老鼠变胖了 |
| 729 | but the red are the knockout mice | 但红色是击倒老鼠 |
| 730 | 减少的PLA2G7 | |
| 731 | and that these animals are partially protected from obesity. | 并且这些动物被部分保护免受肥胖. |
| 732 | I will not go into the details, | 我不会说细节 |
| 733 | but just to quickly tell you that PLA2G7, | 但为了迅速告诉你PLA2G7, |
| 734 | if you reduce this amount, | 如果你减少这个数量, |
| 735 | you reduce the comparing this band to here, | 把这个带子比作这里 |
| 736 | this is active caspase one. | 这是活塞1。 |
| 737 | So reduction in PLA2G7 reduces the NLRP3 inflammasome. | 因此PLA2G7的减少会减少NLRP3的炎症. |
| 738 | Remember that the molecule, | 记住,分子, |
| 739 | the pattern recognition receptor that I told you | 我告诉过你的图案识别受体 |
| 740 | right from the start is very critical | 从一开始就非常关键 |
| 741 | for aging and inflammation. | 为老化和炎症。 |
| 742 | And here is the structure of the thymus. | 这是胸腺的结构 |
| 743 | So remember thymus ages faster | 所以记住你的胸肌年龄越快 |
| 744 | and then all other organs, it becomes smaller | 然后所有其他器官都变小了 |
| 745 | and the thymus basically loses its architecture. | 胸腺基本上失去了它的建筑结构。 |
| 746 | There is a lot of fat that's present. | 有很多脂肪存在。 |
| 747 | Cortex和金属被抹去 | |
| 748 | and if you compare wild type animals on top | 如果你比较上面的野生动物 |
| 749 | to the knockout animals on the bottom, | 对击倒动物的底部, |
| 750 | you see that the thymus are better. | 你看,胸腺是更好的。 |
| 751 | You can see the structure of these animals is much better. | 你可以看到这些动物的结构要好得多. |
| 752 | And so this work was published early this year | 这部作品今年年初出版 |
| 753 | and this is a commentary that was written by my colleagues, | 这是我同事写的评论, |
| 754 | basically suggesting that if you reduced PLA2G7, | 基本上暗示如果你减少PLA2G7, |
| 755 | what we found that in this case, | 我们发现在这个案子里 |
| 756 | you can mimic several aspects of calorie restriction in mice. | 可以模仿小鼠卡路里限制的几个方面. |
| 757 | So remember there's a target | 记住,有个目标 |
| 758 | that we found from humans first, okay? | 我们先从人类那里找到的,好吗? |
| 759 | It is associated with improvements, | 它与改进有关, |
| 760 | but then we reduced it to show causal effect, | 但是我们缩小了它 以显示因果关系, |
| 761 | that it actually improves function | 它可以真正改善功能 |
| 762 | in many of these disease conditions, okay? | 在很多这样的疾病条件下,好吗? |
| 763 | So here, the key point is for you to remember | 关键在于要记住 |
| 764 | is that the immunometabolic response | 是免疫细胞反应 |
| 765 | that is induced by calorie restriction in humans | 由卡路里在人体内的限制引起的 |
| 766 | can produce this anti-inflammatory target | 可以产生这个防炎目标 |
| 767 | 称为PLA2G7. | |
| 768 | And this study has also shown that calorie restriction | 这份研究还显示卡路里限制 |
| 769 | in human beings actually works, okay? | 在人实际上工作,好吗? |
| 770 | And it can in fact rejuvenate certain organs | 它实际上可以恢复某些器官的活力 |
| 771 | that we thought are lost forever, | 我们曾以为是永恒的, |
| 772 | for example, the thymus by increasing thymal poesis. | 例如,通过增加胸腺波氏症的胸腺。 |
| 773 | I will end because we are running out of time | 我会结束,因为我们没有时间了 |
| 774 | and I don't want to overload you with too much data, | 我不想给你太多数据 |
| 775 | but just summarize one more target that we discovered. | 但只是总结一下我们发现的另一个目标。 |
| 776 | I will just show you the summary slide of that, | 我给你们看这个的简略幻灯片 |
| 777 | which is this target called as protein called as SPARC, okay? | 这个目标被称为蛋白质 叫做SPARC,好吗? |
| 778 | This protein is also inhibited by calorie restriction. | 这种蛋白质也受到卡路里限制的抑制. |
| 779 | This work was done by my colleague, Soonjin Ryu, | 这项工作是由我的同事 龙舜津完成的 |
| 780 | who just started his own laboratory in Korea. | 刚刚在韩国开办了自己的实验室 |
| 781 | So what Soonjin found was | 所以舜津发现的是 |
| 782 | that when people are calorie restricted, | 当人们被禁锢的时候, |
| 783 | the levels of SPARC go down, okay? | SPARC的水平下降,好吗? |
| 784 | But here the SPARC is made almost exclusively in humans, | 但这里的SPARC几乎完全是人类制造的, |
| 785 | or not exclusively, but I would say predominantly | 或不只是, 但我主要要说 |
| 786 | by fat cells or adipocytes. | 由脂肪细胞或二聚细胞。 |
| 787 | So when one is in negative energy balance | 所以当一个人在负能量平衡 |
| 788 | or calorie restriction, the levels of SPARC go down. | 或者卡路里限制, SPARC的水平下降。 |
| 789 | When you are in positive energy balance, like in obesity, | 当你处于正能量平衡状态, 就像肥胖, |
| 790 | when there's too much calories that you're consuming, | 当有太多的卡路里 你消耗, |
| 791 | SPARC levels go up, okay? | SPARC水平上升,好吗? |
| 792 | When SPARC levels go down, it reduces inflammation. | 当SPARC水平下降时,会减少炎症. |
| 793 | It increases the tissue repair | 它会增加组织修复 |
| 794 | and also promotes homeostasis | 并且还提倡居家癖 |
| 795 | by increasing the anti-inflammatory response | 通过增加防炎反应 |
| 796 | 在宏phages,好吗? | |
| 797 | When SPARC levels are higher, | 当SPARC水平更高时, |
| 798 | 然后SPARC激活这些宏phages, | |
| 799 | making them more pro-inflammatory, | 使他们更加亲火, |
| 800 | producing more inflammation, increasing, sorry, | 产生更多的炎症, 增加,对不起, |
| 801 | reducing tissue repair and impairing the tissue function. | 减少组织修复和损害组织功能。 |
| 802 | SPARC如何运作? | |
| 803 | So what Soonjin drew discovered was | 索金画的就是 |
| 804 | 脂肪组织使SPARC, | |
| 805 | and the SPARC acts on toll-like receptor four. | 和SPARC作用于类似收费受体四. |
| 806 | And when it does that, | 当它这样做的时候, |
| 807 | it activates two arms of the TLR4 pathway, okay? | 它激活了TLR4路径的两只手臂,好吗? |
| 808 | 这里有一个臂,TRF-TBK1-IRF路径。 | |
| 809 | And what it does is actually induces interferon response, | 它所做的是诱导干扰反应 |
| 810 | okay, which is a very interesting molecule | 好吧,这是一个非常有趣的分子 |
| 811 | involved in controlling viral infections, | 参与控制病毒感染, |
| 812 | but also important in causing disease. | 而且对引起疾病也很重要 |
| 813 | And when it activates the MID88 arm of the TLR pathway, | 当它激活TLR路径的MID88臂时, |
| 814 | SPARC then activates pro-inflammatory cytokines, | SPARC然后激活亲炎细胞基, |
| 815 | IL-6, IL-1-beta, and TNF-alpha causing more inflammation. | IL-6,IL-1-β,以及TNF-α引起更多炎症. |
| 816 | So what we found was that if you can reduce SPARC, | 所以,我们发现 如果你可以减少SPARC, |
| 817 | which decreases, which decreased in people | 人口减少的减少 |
| 818 | upon calorie restriction, | 依卡路里的限制, |
| 819 | then you can actually reduce inflammation. | 然后可以减少炎症 |
| 820 | And here is the mechanism that I just explained to you. | 我刚刚向你解释了这个机制。 |
| 821 | So the take-home point of this slide is here, | 因此,这个幻灯片的取回点在这里, |
| 822 | that first you have to, if somebody argues | 首先,如果有人争论 |
| 823 | whether calorie restriction is relevant | 卡路里限制是否相关 |
| 824 | to human biology or not, | 无论人类的生物学与否, |
| 825 | I think the answer is here and the debate is over. | 我认为答案在这里,辩论已经结束。 |
| 826 | Indeed, CR or negative energy balance | 事实上,CR或负能量平衡 |
| 827 | is very relevant to human biology, | 与人类生物学非常相关 |
| 828 | as has been shown from this clinical trial. | 从临床试验中可以看出 |
| 829 | Other thing very interesting is that | 还有一件有趣的事是 |
| 830 | you just have to limit your calorie intake by just 15%, | 你只需要把卡路里摄入量限制在15% |
| 831 | okay? | 好吗? |
| 832 | It doesn't matter what you're eating in this case | 这个案子你吃什么不重要 |
| 833 | or when you're eating it, | 或者当你吃的时候, |
| 834 | which obviously not everyone can do. | 这显然不是每个人都能做的。 |
| 835 | And what we are trying to do is study | 我们想要做的是学习 |
| 836 | how this happens so that we can identify | 如何发生这种情况 以便我们能够识别 |
| 837 | how the mechanism of CR can be harnessed | 如何利用公司责任机制 |
| 838 | so that we can identify new targets or new drugs | 这样我们可以确定新的目标或新的药物 |
| 839 | that could give us the beneficial effect | 这会给我们带来好处 |
| 840 | of calorie restriction | 卡路里限制 |
| 841 | without actually having to do calorie restriction. | 而不需做卡路里限制。 |
| 842 | So I showed you the data from two of these molecules, | 我给你看了其中两个分子的数据 |
| 843 | PLA2G7和SPARC(英语:SPARC). | |
| 844 | And I think only time now will tell what will happen | 我想现在只有时间 才能知道会发生什么 |
| 845 | when we do clinical trials with these two molecules, | 当我们用这两种分子做临床试验时 |
| 846 | whether it is clinically beneficial or not | 无论临床上是否有益 |
| 847 | in human beings or in aging individuals. | 人类或老年人。 |
| 848 | So I will stop here and I have thanked people | 所以我就到此为止,谢谢大家 |
| 849 | that have done this work as I went along. | 已经做了这项工作,我走了。 |
| 850 | Most of this work obviously cannot be done | 大部分工作显然无法完成 |
| 851 | unless or until I have this amazing group of people, | 除非或直到我有这么一群人 |
| 852 | my colleagues, students and post-docs. | 我的同事,学生和博士后。 |
| 853 | The most of the calorie restriction work | 大部分卡路里限制工作 |
| 854 | was done in the lab by Yunhee Yun. | 由云熙云在实验室完成. |
| 855 | The identification of the changes | 确定变化 |
| 856 | in the adipose immune system was done by Dr. Emily Goldberg. | 在脂肪免疫系统中是由艾米莉·戈德伯格博士完成的. |
| 857 | The work in relation to identification of SPARC | B. 与确定SPARC有关的工作 |
| 858 | was done by Dr. Olga Spadaro, | 由奥尔加·斯帕达罗博士完成 |
| 859 | 现在在AstraZeneca做高级科学家 | |
| 860 | 和识别SPARC 是一个Cremimetic, | |
| 861 | this work was done by my colleague, Xun Jin Ru, | 这项工作由我的同事许振鲁完成 |
| 862 | who is now running his own laboratory | 他现在经营自己的实验室 |
| 863 | and several of my colleagues at Yale | 以及我在耶鲁的几位同事 |
| 864 | and several other places in the country. | 以及该国其他几个地方。 |
| 865 | So I thank you very much for your attention. | 因此,我非常感谢大家的注意。 |
| 866 | I will be happy to answer any questions that you may have | 我很乐意回答你的任何问题 |
| 867 | and I will stop sharing the screen so that you can see me | 我会停止分享屏幕 这样你就能看到我 |
| 868 | and if you have any questions you can ask. | 如果你有任何问题可以问 |
| 869 | Great, thank you so much. | 太好了,非常感谢。 |
| 870 | Such amazing research that you're doing. | 你所做的如此惊人的研究。 |
| 871 | And I'm sure there are lots of questions that people have. | 我敢肯定,人们有很多问题。 |
| 872 | So feel free to raise your hand and I can call on people | 随便举起你的手,我可以叫人来 |
| 873 | or you can leave your questions in the chat box | 也可以把问题放在聊天框里 |
| 874 | and we'll try our best to get to all of them. | 我们会尽力找到他们 |
| 875 | And I see that Yang Yue has their hand up. | 我看见杨岳举起手来 |
| 876 | So let's start with Yang Yue. | 故先从杨岳. |
| 877 | Thank you so much for sharing your expertise and knowledge | 非常感谢你分享你的专长和知识 |
| 878 | and I have three questions. | 我有三个问题 |
| 879 | First one, regarding the aging. | 第一个,关于老化。 |
| 880 | So what's your opinion about the inflammation and aging? | 你对炎症和衰老有什么看法? |
| 881 | Which one is cause and which one is effect? | 何谓因果? |
| 882 | I feel like it's sort of like the chicken and the egg. | 我觉得有点像鸡和蛋 |
| 883 | And the second question is in your study, | 第二个问题在你的研究中 |
| 884 | you showed the adipose tissue. | 你展示了脂肪组织。 |
| 885 | I wonder which one, like white adipose tissue | 我想知道哪一个,像白脂肪组织 |
| 886 | or brown adipose tissue you looked at. | 或棕色脂肪组织,你看。 |
| 887 | And my third question is that calorie restriction | 我的第三个问题是卡路里的限制 |
| 888 | shows really promising effect. | 显示出非常有希望的效果。 |
| 889 | I wonder whether you also looked at individual metabolism | 我想知道你是否也研究过个人新陈代谢 |
| 890 | because given that everyone has a different metabolism | 因为每个人都有不同的代谢 |
| 891 | and digestion, I wonder whether it could cause | 和消化,我想知道 它是否会导致 |
| 892 | any kind of effect on the inflammation marker | 对炎症标记的任何影响 |
| 893 | or something else. | 或别的东西。 |
| 894 | Thank you. | 谢谢 |
| 895 | Thank you, Yang Yue. | 谢谢杨岳. |
| 896 | It was all three are excellent questions. | 这三个问题都很好 |
| 897 | First, always the question of egg and chicken. | 首先,总是蛋和鸡的问题。 |
| 898 | What comes first in terms of causing a particular disease? | 在引起某种疾病方面,首先是什么? |
| 899 | What is cause? | 原因为何? |
| 900 | What is the effect? | 有什么影响? |
| 901 | To be honest, the answer is we don't have the answer | 老实说,答案是我们没有答案 |
| 902 | as to what is causing inflammation | 以什么为炎症? |
| 903 | and what is causing aging. | 以及导致衰老的事物。 |
| 904 | Because inflammation is not going to happen | 因为炎症不会发生 |
| 905 | unless you have cellular damage in this case, | 除非你有细胞损伤 在这种情况下, |
| 906 | inflammation of aging. | 衰老的炎症。 |
| 907 | And cellular damage will not happen if you live long enough | 如果你活得够久 细胞就不会受损 |
| 908 | because cells are continuously active. | 因为细胞持续活动。 |
| 909 | You can imagine if you're a cardiomyocyte, | 你可以想象,如果你是一个心肌细胞, |
| 910 | you start beating it when you are born | 你出生后就开始打它 |
| 911 | and you're beating till you're dead. | 你会一直打到死 |
| 912 | So those cells are producing | 所以这些细胞正在产生 |
| 913 | these damage associated molecular patterns | 这些破坏 相关的分子模式 |
| 914 | that eventually are sensed by the macrophages | 最终被宏phages所感知 |
| 915 | to cause inflammation. | 导致炎症。 |
| 916 | And that inflammation further impairs organ function | 这种炎症会进一步损害器官功能 |
| 917 | because it extracts a cost from an organ | 因为它从器官中提取成本 |
| 918 | when those inflammatory cytokines | 当这些炎热的细胞皮 |
| 919 | are persistently increase. | 不断增加。 |
| 920 | So I think they both go hand in hand | 所以我觉得他们两个是并肩作战的 |
| 921 | because we have shown | 因为我们已经显示 |
| 922 | that if you actually reduce NLRP3 in flamosome, | 如果你真的减少 NLRP3 在闪亮, |
| 923 | you can delay the onset of aging. | 您可以推迟衰老的开始。 |
| 924 | You can increase the health span. | 您可以增加健康范围。 |
| 925 | There is also data from the National Institute | 还有来自国家研究所的数据。 |
| 926 | on Aging's Intervention Testing Program | 老年人干预测试方案 |
| 927 | that a drug that inhibits inflammation NHDGA | 一种抑制炎症的药物 NHDGA |
| 928 | actually increases lifespan. | 实际上延长寿命。 |
| 929 | So that would suggest some cause, | 因此,这意味着一些原因, |
| 930 | but I am more in the camp that they go, | 但我更在营地 他们去, |
| 931 | I think side by side | 我想并肩作战 |
| 932 | because that cellular damage has to happen. | 因为必须发生细胞损伤 |
| 933 | I think your second question was what fat is that? | 你的第二个问题是什么脂肪? |
| 934 | White fat or the brown fat? | 白脂肪还是棕脂肪? |
| 935 | Yeah, that's all white fat. | 是啊,这是所有的白色脂肪。 |
| 936 | The best little fat that we accumulate with age | 最好的小脂肪 我们积聚随着年龄 |
| 937 | and with increased obesity is all white fat. | 肥胖症增加后,都是白脂肪。 |
| 938 | Excuse me. | 对不起。 |
| 939 | And the visceral white fat is the one | 粘着的白色脂肪就是它 |
| 940 | that is a major source of inflammation with aging | 这是老化的主要发炎源 |
| 941 | because of alterations in the immunological nature | 因为免疫学的改变 |
| 942 | of the white adipose tissue. | 白色脂肪组织。 |
| 943 | Your third question was how can individual metabolism | 你的第三个问题是 个人如何代谢 |
| 944 | in people that is different | 在不同的人当中 |
| 945 | contribute to effect or lack of effect | 促成效果或不效果 |
| 946 | of calorie restriction? | 对卡路里的限制? |
| 947 | That's a good question. | 问曰. |
| 948 | We don't have the data Yan Yu | 我们没有燕羽的数据 |
| 949 | because this clinical trial was not designed to do that. | 因为这次临床试验不是设计这样做的。 |
| 950 | So the way the people were selected | 所以人们的选择方式 |
| 951 | was exactly to address the question that you have, | 完全是为了解决你的问题, |
| 952 | which is we don't want people | 也就是我们不想要人 |
| 953 | to have different type of metabolism. | 拥有不同种类的新陈代谢。 |
| 954 | We want everybody in the trial to be more or less the same | 我们希望审判中的每个人 都大致一样 |
| 955 | so that we can understand what is really causal. | 这样我们才能理解什么才是真正的因果关系。 |
| 956 | So everybody that was in the trial | 所以所有在审判中的人 |
| 957 | was within the same age limit. | 年龄限制相同。 |
| 958 | They all were metabolically healthy. | 他们都在代谢健康。 |
| 959 | They were all normal. | 他们都是正常的。 |
| 960 | But indeed that's, I think a very important point as to, | 但事实上,我认为非常重要的一点是, |
| 961 | because we know that some of us lose weight easily. | 因为我们知道我们有些人很容易减肥。 |
| 962 | Some do not lose weight very easily. | 有些人不会轻易减肥。 |
| 963 | The energy expenditure between people can be different. | 人与人之间的能源支出可能有所不同. |
| 964 | Obviously our gut microbiome, | 显然我们的肠胃微生物 |
| 965 | which contributes to changes in our metabolism | 有助于改变我们的新陈代谢 |
| 966 | is different between different individuals. | 不同个体之间不同。 |
| 967 | Therefore, I think what was really interesting | 所以,我觉得真正有趣的是 |
| 968 | from this clinical trial | 从这次临床试验中 |
| 969 | was how solid or how tight the data was. | 数据有多可靠或有多紧。 |
| 970 | Despite our individual differences, | 尽管我们个人有分歧 |
| 971 | individual genetic differences. | 个人基因差异。 |
| 972 | Obviously these are not inbred mice | 这些显然不是小老鼠 |
| 973 | with 99% genetically identical genomes. | 基因组99%相同 |
| 974 | Still these people, if you look at the transcriptomics | 还是这些人,如果你看的字典 |
| 975 | are very, very similar in their response | 他们的反应非常,非常相似 |
| 976 | to restriction of calories. | 限制热量。 |
| 977 | I think additional studies would have to be done | 我想还需要做更多的研究 |
| 978 | where you can test people at the baseline | 您可以在基线测试人员 |
| 979 | to see how different they are | 看他们有多不同 |
| 980 | and then follow them with certain interventions, | 然后依附他们, |
| 981 | metabolic interventions, even calorie restriction | 代谢干预,甚至卡路里限制 |
| 982 | and how that affects the outcome | 如何影响结果 |
| 983 | of that particular intervention. | 特别的干预。 |
| 984 | I think those studies would potentially | 我认为这些研究有可能 |
| 985 | have to be done in future. | 未来必须完成。 |
| 986 | Yeah, that's great. | 是啊,这是伟大的。 |
| 987 | And of time I lost, my last question is like, | 时间我输了,我最后一个问题就是, |
| 988 | what kind of food you can suggest to people in general | 什么样的食物你可以建议 普通人 |
| 989 | to promote the healthy aging? | 推动健康的衰老? |
| 990 | Because my study is trying to focus on the flavor noise | 因为我的书房是想把精力集中在风味噪音上 |
| 991 | of phytonutrients, chemical, just the two. | 植物营养,化学,只有两种 |
| 992 | And not like delay rate aging. | 而不是像延迟率老化。 |
| 993 | Extend the house living span for people. | 扩大房屋的居住范围给人们。 |
| 994 | So do you, as a immunologist, | 你也一样,作为一个免疫学家, |
| 995 | do you have any recommendations for the diet of food? | 你有关于饮食的建议吗? |
| 996 | Thank you. | 谢谢 |
| 997 | Yang Yu, I have zero recommendations | 杨瑜,我建议你不要 |
| 998 | because I'm not a public health doctor | 因为我不是公共卫生医生 |
| 999 | who gives nutritional advice to people. | 他们为人们提供营养建议。 |
| 1000 | And my job is to study and do science | 我的工作是学习和做科学 |
| 1001 | and study this intervention that extends lifespan. | 研究延长寿命的干预措施。 |
| 1002 | However, Yang, we should do | 不过,杨哥,我们该去 |
| 1003 | what our grandmother told us, right? | 我们的祖母告诉我们的,对不对? |
| 1004 | Yeah. | 对 |
| 1005 | If you eat enough vegetables, enough fruits, | 如果你吃足够的蔬菜,足够的水果, |
| 1006 | and if you eat a little bit less | 如果你少吃一点 |
| 1007 | and walk a little bit more, we'll be fine. | 再多走一点 我们会没事的 |
| 1008 | But I think humans find it very difficult | 但我觉得人类很难接受 |
| 1009 | to do these things. | 做这些事情。 |
| 1010 | And I think we know the problem right now, | 我想我们现在知道了问题所在 |
| 1011 | at least in Europe and US, | 至少在欧洲和美国, |
| 1012 | also in several developing countries, | 在一些发展中国家, |
| 1013 | including India, is this new Western diet, | 包括印度,这是新的西方饮食, |
| 1014 | which obviously has lots of negative effects | 这显然会产生很多负面影响 |
| 1015 | because lots of saturated fats and fried foods. | 因为很多饱和脂肪和炸食品。 |
| 1016 | Ultra-processed foods. | 超加工食品. |
| 1017 | Exactly, exactly. | 没错,没错。 |
| 1018 | Because our diets have changed in the modern world. | 因为我们的饮食在现代世界已经发生了变化. |
| 1019 | That is contributing to a further increase in diseases. | 这导致疾病进一步增加。 |
| 1020 | But I think the evidence, like you mentioned, flavor noise, | 但我认为证据,像你提到的, 味道噪音, |
| 1021 | I mean, these things are present | 我的意思是,这些东西是存在的 |
| 1022 | in our vegetables and food and our fruits. | 我们的蔬菜、食物和水果。 |
| 1023 | And consumption of these things obviously helps. | 消耗这些东西显然有帮助。 |
| 1024 | But what this trial basically is showing us | 但这次审判基本上告诉我们 |
| 1025 | is that if you activate the pathways | 是,如果你激活路径 |
| 1026 | that are going to act on your adipose tissue | 那会影响你的脂肪组织 |
| 1027 | that stores the fuel, | 储存燃料, |
| 1028 | if you activate the mitochondrial pathways | 如果你激活线粒体路径 |
| 1029 | that increase fatty acid oxidation, | 增加脂肪酸氧化, |
| 1030 | that is where I think the beneficial effects lie. | 这正是我认为有益效果所在。 |
| 1031 | That's where, that's the reason why the benefits are there. | 这就是好处存在的原因 |
| 1032 | And I think people have done that. | 我认为人们已经这样做了。 |
| 1033 | For example, if people are in the same, | 例如,如果人们处于同一状态, |
| 1034 | if they consume same energy and they expend same energy, | 如果他们消耗同样的能量 消耗同样的能量 |
| 1035 | because in many studies, exercise has no effects, | 因为在许多研究中,运动没有效果, |
| 1036 | no beneficial effects. | 没有有益的效果。 |
| 1037 | And the reason for this is simple, | 原因很简单 |
| 1038 | because unless you mobilize your adipose tissue | 因为除非你动员你的脂肪组织 |
| 1039 | by fatty acid oxidation, | 通过脂肪酸氧化, |
| 1040 | you don't really get beneficial effects. | 你不会真的得到有益的效果。 |
| 1041 | So it means that we have to be negative energy balance | 也就是说我们必须是负能量平衡 |
| 1042 | at least for some time. | 至少有一段时间 |
| 1043 | Yeah, that's really informative. | 是啊,这是真正的信息。 |
| 1044 | Thank you so much. | 非常感谢 |
| 1045 | Thank you. | 谢谢 |
| 1046 | Thank you, Yang Yuan. | 谢, 杨元. |
| 1047 | I feel like he probably asked the question | 我觉得他可能问了个问题 |
| 1048 | that a lot of people are wondering. | 很多人在想这个 |
| 1049 | It's sort of, what can I do to limit calorie? | 我该怎么限制卡路里? |
| 1050 | It was interesting that you mentioned | 很有趣,你提到 |
| 1051 | that it didn't seem like with calorie restriction, | 似乎没有卡路里的限制, |
| 1052 | it mattered what kinds of food you were kind of worrying. | 关乎你担心的食物种类 |
| 1053 | And as long as you restrict. | 只要你限制。 |
| 1054 | And I was wondering also, at least anecdotally, | 我在想,至少是传闻 |
| 1055 | it seems like when people age, | 似乎人们老了, |
| 1056 | naturally your body tends to want to eat less, right? | 自然,你的身体倾向于 吃少,对不对? |
| 1057 | Your appetite decreases and things like that. | 你的胃口会下降 类似的东西。 |
| 1058 | Is there some connection there? | 有什么联系吗? |
| 1059 | Is that a natural response | 这是自然反应吗? |
| 1060 | that's been developed over time in evolution | 这在进化过程中已经发展出来 |
| 1061 | that sort of maybe like the body is telling us | 也许像尸体告诉我们 |
| 1062 | that that is the way to go to increase health? | 这就是提高健康的方法? |
| 1063 | That's a very, very good question, Devan. | 这是一个非常,非常好的问题,Devan。 |
| 1064 | I don't think I have the answer. | 我想我没有答案 |
| 1065 | I can only speculate. | 我只能猜测。 |
| 1066 | I don't think that's an evolutionary response. | 我不认为这是一个进化反应。 |
| 1067 | Because if you really look at human evolution, | 因为如果你真的看 人类进化, |
| 1068 | just till two centuries ago, | 直到两个世纪前 |
| 1069 | the average human lifespan was what, 40 years, 45 years. | 人类的平均寿命是40岁45岁 |
| 1070 | So we just never lived long enough | 所以,我们只是从来没有 活得足够长 |
| 1071 | for those evolutionary mechanisms to engage in my view. | 让这些进化机制 进入我的观点。 |
| 1072 | So I think what is happening, | 所以,我认为发生了什么, |
| 1073 | some people believe aging is programmed. | 有些人认为老化是编程的 |
| 1074 | I'm not very sure how programmed it is. | 我不确定这是怎么编程的 |
| 1075 | I think lots of these things are stochastic | 我觉得很多这些东西很诡异 |
| 1076 | because I don't think we've ever had enough time | 因为我觉得我们没有足够时间 |
| 1077 | because evolution is prioritizing reproduction. | 因为进化是优先复制 |
| 1078 | Our main purpose on earth is to come in | 我们地球的主要目的就是进来 |
| 1079 | and reproduce and die. | 然后繁殖和死亡 |
| 1080 | That's how the species have basically evolved. | 物种基本上就是这样进化的. |
| 1081 | So, and living longer has not been the priority. | 因此,长寿不是当务之急。 |
| 1082 | So what happens, so if, you know, | 所以,会发生什么, 所以,如果,你知道, |
| 1083 | we know that elderly, one of the major problems | 我们知道,老人,一个主要问题 |
| 1084 | or the problems or at least the symptoms is loss of appetite. | 或者问题 或者至少症状是食欲丧失 |
| 1085 | People have anorexia, people don't eat enough. | 人有厌食,人食不足. |
| 1086 | Whether that's beneficial or whether that's pathological, | 不管是有益还是病理 |
| 1087 | I am not very sure in my view, | 我觉得不太确定 |
| 1088 | because also if you look at the time | 因为如果你看看时间 |
| 1089 | when individuals lose their appetite, | 当人们失去胃口的时候, |
| 1090 | they've also lost substantial amount of muscle mass | 他们也损失了大量的肌肉质量 |
| 1091 | and overall body mass. | 身体整体质量 |
| 1092 | So, you know, an 85 year old, | 所以,你知道, 一个85岁, |
| 1093 | a 90 year old person is not the same physiologically. | a 90岁的人在生理上不同。 |
| 1094 | So it's fuel consumption. | 所以这是燃料消耗。 |
| 1095 | You know, the requirement of energy it has is already less. | 你知道,它拥有的能量需求已经更少了。 |
| 1096 | And, but yes, I mean, in my view, | 但是 是的 我认为 |
| 1097 | it is a pathological response because, | 这是一个病理反应,因为, |
| 1098 | you know, the things that people used to like, | 你知道,人们喜欢的东西, |
| 1099 | they no longer like, for example, | 他们不再喜欢,例如, |
| 1100 | whether that is part of the biology, it's not very clear, | 这是否是生物学的一部分, 不是很清楚, |
| 1101 | but this is certainly something that needs to be studied. | 但这肯定是需要研究的 |
| 1102 | I'm of the view that, you know, for example, | 我认为,例如,你知道, |
| 1103 | when somebody is already restricting calories | 当有人已经限制卡路里时 |
| 1104 | and is eating less with age, | 并随着年龄而减少饮食, |
| 1105 | doing further of these things | 继续做这些事情 |
| 1106 | could potentially be potentially be harmful. | 有可能是有害的。 |
| 1107 | So when these diet interventions are used | 所以当这些饮食干预被使用 |
| 1108 | or how they affect people at different ages | 或如何影响不同年龄的人 |
| 1109 | is something that needs to be studied | 是需要研究的东西 |
| 1110 | and is going to be studied soon. | 并即将被研究。 |
| 1111 | Great, thank you. | 很好,谢谢 |
| 1112 | In the chat box, Henry had asked, | 在聊天盒里,亨利问, |
| 1113 | there's a study conducted in Europe that says, | 在欧洲进行的研究表明 |
| 1114 | you know, human life expectancy can be up to 120 years. | 人类的寿命可达120岁 |
| 1115 | Sort of, are we expecting that? | 算是吧,我们期待吗? |
| 1116 | Are we expecting, you know, | 我们期待,你知道, |
| 1117 | discovering the fountain of youth | 发现青春之泉 |
| 1118 | and being able to live much longer? | 还能活得更久吗? |
| 1119 | You know, I'm an optimist, Devan. | 你知道,我是一个乐观主义者,Devan。 |
| 1120 | I do think, I don't know about the fountain of youth, | 我觉得,我不知道 喷泉的青春, |
| 1121 | there are several people, I think, | 有几个人,我想, |
| 1122 | who are making lots of hyperbolic statements in our area, | 他们正在我们地区发表大量双曲言论, |
| 1123 | which I think is unfortunate | 我觉得很不幸 |
| 1124 | because we don't really have data | 因为我们没有数据 |
| 1125 | to really say much at this point of time. | 在这个时候说很多话 |
| 1126 | The only thing we can say is that, you know, | 我们只能说,你知道, |
| 1127 | the modern science is making, I think, | 我认为现代科学正在形成 |
| 1128 | some significant advances. | 一些重大进展。 |
| 1129 | And it is very difficult to predict how science goes. | 很难预测科学是如何发展的。 |
| 1130 | I really don't know where the next big discovery | 我真的不知道下一个大发现在哪里 |
| 1131 | is gonna come from. | 将来自。 |
| 1132 | Maybe some people have, you know, a special magic wand | 也许有些人有特别的魔杖 |
| 1133 | where they can shake it and, you know, | 他们可以摇动它,你知道, |
| 1134 | find out what's the next big thing. | 找出下一个大问题 |
| 1135 | I don't know, but I'm an optimist. | 我不知道 但我是个乐观主义者 |
| 1136 | And I think based on the work that is going on | 我想基于 正在开展的工作 |
| 1137 | from several really exciting laboratories all over the world, | 来自世界各地几个令人兴奋的实验室 |
| 1138 | I have a feeling that, overall, | 我有一种感觉,总的来说, |
| 1139 | that eventually we would have tools | 最终我们会有工具 |
| 1140 | that would reduce our disease burden | 这会减轻我们的疾病负担 |
| 1141 | and most likely, in my view, | 很可能,在我看来, |
| 1142 | extend our ability to live longer. | 延长我们的寿命 |
| 1143 | Whether that 120 years is the terminal limit | 这120年是不是终点站 |
| 1144 | is really not sure. | 实在不确定。 |
| 1145 | I'm not sure because, you know, | 我不知道,因为,你知道, |
| 1146 | lots of those are mathematical models. | 很多都是数学模型。 |
| 1147 | Unless you do a clinical trial, there's no way to know. | 除非你做临床试验,否则不可能知道 |
| 1148 | And so you could say either way | 所以你可以随便怎么说 |
| 1149 | that you cannot live more than 120 | 你活不到120岁 |
| 1150 | or somebody can say, oh, you can live beyond 120. | 或者有人会说 你可以活到120岁 |
| 1151 | Fact is, nobody actually knows. | 事实上 没人知道 |
| 1152 | And nobody will know for at least 100, | 没有人会知道至少100, |
| 1153 | for another 150 years till you do the study. | 再待150年,直到你完成研究。 |
| 1154 | And the people who are making those comments | 而那些发表这些评论的人 |
| 1155 | probably would be dead by then. | 那时可能已经死了 |
| 1156 | So I'll end here with that remark. | 所以,我在这里结束 说。 |
| 1157 | Great, thank you so much. | 太好了,非常感谢。 |
| 1158 | I think because of time, I think we'll end there. | 我想因为时间的关系,我想我们会在那里结束。 |
| 1159 | Thank you so much for a fascinating discussion. | 非常感谢你这么精彩的讨论 |
| 1160 | And I would say quite a new paradigm for us to | 我会说一个全新的模式,让我们 |
| 1161 | think about disease, not in terms of individual specific diseases, but just to think of aging | 想想疾病,不是从个别疾病的角度,而是从老化的角度 |
| 1162 | overall as sort of that major risk factor. | 总体来说是这种主要风险因素。 |
| 1163 | So, and I guess the main takeaway is just a small | 所以,我想主 外卖只是小 |
| 1164 | amount of calorie restriction can improve health, you know, simply put. | 大量的卡路里限制 能够改善健康,你知道的,简单的放。 |
| 1165 | Thank you so much again, | 再次谢谢你 |
| 1166 | thank you everybody for joining us. | 谢谢大家加入我们 |
| 1167 | And I will unmute everybody so that they can all thank you | 我会解开大家的怨恨,让他们都能感谢你 |
| 1168 | personally. | 就个人而言 |
| 1169 | Thank you, Devin. | 谢谢你,德文 |
| 1170 | Thanks, thanks everyone. | 谢谢大家 |
| 1171 | To all my colleagues, many of you I | 对我所有的同事,你们中的很多人,我 |
| 1172 | know are watching this late in the evening. | 晚上很晚才看电影 |
| 1173 | So thanks for joining. | 谢谢你的加入 |
| 1174 | Thanks for your questions | 谢谢你的问题 |
| 1175 | and your attention. | 和你们的注意力。 |
| 1176 | And hopefully we'll have a chance to reconnect at some other time. | 希望我们有机会在别的时间重新连接 |
| 1177 | Thank | 谢谢 |
| 1178 | you. | 你们 |
| 1179 | Thank you everybody. | 谢谢大家 |
| 1180 | Thank you. | 谢谢 |
| 1181 | Thank you for sharing. | 谢谢你的分享 |
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