Aubrey de Grey:我们能够避免老化

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http://dotsub.com/view/eb6d612f-e013-4cbc-9026-29efd8f1d397
Aubrey de Grey:我们能够避免老化
十八分钟是一个非常紧的时间限制， 因此我直入主题，讲重点的， 我将马上开始。 好，我要谈五个不同的事情。 一，我要谈谈为什么抗老化是可行的。 二，我要谈谈为什么我们必须打起精神， 多讨论这个课题，并且发觉我们应该指望战胜老化。 当然，三，我也会谈谈战胜老化的可行性。 四，我要谈谈为什么我们在人类抗老化上采取的行动这么的认命， 以为都是注定的。 然后，第五，我也许在这个节目的下半段的时间谈谈 我们如何证明这个[对战胜老化]漠不关心以及以为是注定的心态是错误的， 并且实际上做点什么事来纠正这个错误。
这第五点，我会用两个步骤来谈论。 第一个步骤是 如何从一个相对适中的延长寿命治疗科技 - 我这就把它定义为可延长三十年寿命， 并且在已经是中年年龄的人开始应用 – 直到一个能真正被称为战胜老化问题的程度。 也就是说，实质上消除了你多大年纪， 以及你在下一年死去或 生病的可能性之间的关系。 最后一件事[第五件事情， 第二个步骤]我要谈的是如何实现过度步骤， 那个能给我们每一个人延长三十年寿命的治疗科技。
好，我就从为什么要延长人类的寿命开始。 现在，我想问一个问题。 观众席里有谁赞成疟疾是有利的？请举手。 好，这很简单。 行。行。请不知道疟疾 是好事还是坏事的人举手？ 好。所以，我们都认为，疟疾是一件坏事。 这是一个非常好的消息，因为我原以为这就是答案。 现在我希望你们想一想 我们认为疟疾是一件坏事主要的原因， 是因为疟疾和老化有着共同的特征。 那个特征就是两者都杀死人。 唯一真正的区别是，老龄化杀死的人数比疟疾杀死的多许多。
现在，我喜欢观众，尤其是在英国的观众， 比较一下老化和打猎狐狸。 打猎狐狸是是经过长期斗争 不久前被政府禁止的活动。 我的意思是，虽然我知道富有同情心的观众应该大多数都反对打猎狐狸， 但我们知道，很多人并不是完全被这个逻辑说服。 在我看来，这其实和老化是一个不错的比较。 你知道，很多[郊外]的人说：“你们这些 住在城市的人没有权利告诉我们什么活动可以做什么东西不能做。 这是我们[住在郊外的人]的传统生活方式的一部分， 我们应该有权力继续做它。 这是促进生态健全的，它控制了狐狸数量爆涨。” 但是，政府最终占了上风， 因为大多数的英国公众， 还有国会多数成员， 得出的结论，就是这[打猎狐狸] 是一个文明社会所不能容忍的活动。
我认为，人类衰老也有这些特点， 它是一个不能容忍的活动。 这有什么难明白的？ 这当然不只是生命， （众笑） 这也是有关可以健康的生活下去。 因为无论人们觉得死亡是否好玩[是否应该容忍]， 身体越来越衰弱，悲惨地依赖别人一点都不好玩。 因此，其实这就是我想要对它的[人类衰老]描述。 这[它]是一个全球性恍惚。 这是人们对老龄化作出了 种种令人难以置信的借口。 而且，我的意思是，好吧，我不是在说 这些借口是完全没有价值。 这些借口也有一些好的积极方面。 比如说我们应该思考的种种问题，有规划些， 来尽量减少我们在战胜老化路途上 的不必要的动荡。
但只要如果你真正衡量它们， 这些借口都是完全疯了！ 你知道，这些[借口的]论点 是合理的，值得去关注。 但问题是，这些论点有没有那么危险? 战胜老化的风险 有没有高过 不理会人类老化的代价？ 难道这些[修复老化的风险]如此糟糕， 比每天超过十万人面对早死的命运还糟糕？ 你知道，如果你还没有比这一个说法更强的论点， 那么就不要浪费我的时间。这是我[对反对战胜老化]的看法。
（众笑）
话虽如此，有一种观点有些人认为， 确实是很强，我们就在这儿讨论一下。 人们担心人口过多，他们说， “好吧，如果我们战胜老化，没有人类死亡可言， 或至少是死亡人数变得低得多， 变得只有不小心越过圣吉尔斯河而死[笑话]。 因此，我们不需要有很多孩子， 可是孩子对多数人很重要。” 这是事实。 你知道，很多人试图捏造这个问题， 并给予这样的答案。 我不同意这些答案。我认为它们根本行不通。 我认为这是真的，我们会在这方面面临两难。 我们将必须决定是否有一个低生育水平， 或者高死亡率。 拒绝这些战胜老化治疗，死亡率就会变高[和接受治疗的死亡率相比下]， 当然，在这种情况下我们就能生许多孩子。
我觉得这没问题 – 人类的下一代，有权做出这个选择。 不正确和不应该的是我们现在就替下一代的做出这个选择。 如果因为我们犹豫， 而不开发这些[战胜老化的]疗法， 那么我们就等于判了我们的子孙一个不能永远活着的命运。 本来因为他们够年轻，够健康， 可以获益于这些疗法。 但因为我们的犹豫，没有尽快开发这些疗法 – 我们等于不让这些人有更长的寿命， 我认为这是不道德的。 这是我对人口过多的问题的回应。
好，接下来的是， 为什么我们应该在这一方面积极点？ 最根本的答案是，[潜意识的认同老化是必然的] 亲老化恍惚并不像它看起来的那么笨。 它其实是在应对无法避免的老化时的一个很明智的办法。 老化是可怕的，但它是不可避免的，所以， 我们必须想尽办法把这想法从我们头脑中忘记， 理性地去做我们想要做的事情来改变。 例如，人类会想出这些荒谬的原因 来解释其实老化是件好事。 当然，这些[荒谬]的原因的起因有两个连接部分[一是老化，二是命中注定。] 只要命中注定那个部分在我们的脑海中没那么的肯定， 我们就可以开始对战胜老化采取行动， 这是老化问题的一部分。 这亲老化恍惚常常妨碍人们解决老化这个问题。 这就是为什么我们一定要继续提出以及谈论这个课题， 我甚至会说 – 为了吸引人们的注意力，使人们认识到， 他们在这方面的恍惚， 关于这个话题我就说到这里。
我现在要谈的是第三点，打败老化的可行性。 其根本原因，我想，为什么我们认为老化是不可避免的， 是可以用我在这儿给老化的定义作为总结。 这是一个非常简单的定义。 老化是一种活着的副作用， 也就是说，新陈代谢的副作用。 这并不是一个完全同义重复的声明， 它是一个合理的声明。 老龄化基本上是一个过程，发生在无生命的物体如汽车， 也发生在人类的身上， 尽管我们的身体有很多聪明的自我修复机制， 因为这些自我修复机制还不完善[我们还是会老化]。
基本上，新陈代谢，就是说 [在我们身体里]所有为了让我们能够每一天活着所维持的种种化学过程， 有副作用。 这些副作用会不断的积累，最终导致病理[不可避免的死亡]。 这是一个不错的定义。因此，我们可以这样表达, 我们可以说，大家都知道，我们有着这一系列事件。 而且根据大多数人，对于推迟衰老， 只有两种方法。 这两种方法就是老年学和老年医学。 老年医学医生会在一个人老化过程的后段， 病理越来越明显的时候， 做治疗来尽量阻止老化时间 和副作用积累 并且阻止那么快就造成不可避免地死亡。 当然，这是一个非常短暂的战略，是一个败仗， 因为导致病理[不可避免地死亡]的这些副作用 会随着时间的推移越来越多。
老年学的方法在表面上看起来更充满希望具发展前景， 因为你们也知道，预防胜于治疗。 但不幸的是，我们对新陈代谢的理解非常少。 事实上，我们对生物体的了解少的可怜 – 甚至细胞，我们都不是很懂。 连对细胞如何操作的 基本知识， 例如核糖核酸机能失常， 在仅仅几年前,我们才发现它。 基本上，如果我们要讨论在我们一生中能用到的延长寿命的治疗， 老年学以后将会是一个很好的方法， 但它的时机未到[因为我们对新陈代谢的理解还太少]。 然后呢，这怎么办呢？ 我的意思，这是一个很好的逻辑， 听起来非常有说服力的，不是吗？
但事实并非如此。 在我告诉你为什么不能之前， 我要谈谈我所谓的第二步。 我们假设，如果正如我所说的， 我们 - 假设说今天 – 就拥有能够给现在已是中年，假设说五十五岁的人， 多三十年的健康寿命的治疗方法。 我称这为‘强健人类再生’ 。好。 那么实际上这对于现在不同年龄的人们， 或者相等地，当这些治疗方法到达时 已是不同年龄的人有什么影响呢？ 他们会活多久些呢？ 你可能会认为回答这个问题很简单， 但它并不简单。 我们不能只是说：“好吧，如果他们足够年轻，得益于这些治疗方法， 那么他们就会活[比本来]多三十年的时间。” 这是错误的答案。 而错误的原因是因为进步。
对于我们这方面的治疗， 科学进步有两种。 第一种是突破性的进步， 然后还有第二种就是不断的在那些突破性的进步上做出改良和提高它们的有效率。 这两种科学进步所需的 时间的预测度有很大的不同。 我们很难预测 多久才会有 突破性的进步。 人类很有可能在很多年前就想在天空上飞行了， 可是要等到一九零三年才发现到底怎么飞行。 可是这之后，人类飞行的科技就很有步骤地发展下去。 我认为这是一个很合乎情理才导致了 动力飞行的科技进展。 我们可以想象这些科技发展的每一步都是 上一步的研发人所想不到的。 比起原先每次都递进增值 有进展。
在每个科学突破性的进步后，您都会看到这些有步骤性的发展。 而且在很多科技上都是这样。 比如说电脑，和飞行科技也很类似， 只是发生的时间不同罢了。 您也可以看一看医药保健科技，比如说卫生，疫苗，抗生素， 也有着一样的发展时间表。 因此，我认为其实两个步骤，我刚才称为一个步骤， 并不完全是一个步骤。 事实上，很年轻的人 会从这些实验治疗方法受益， 能使人们的生命适量延长， 即使这些人已经中年，当这些治疗方法来到 人们还可以尝试治疗方法。 他们多数活得足够长来接受改进的治疗方法， 从而使他们多活30年甚至50年。 换句话说，他们将领先于老化的速度。 治疗法比起治疗法中存在的缺陷 改进得更快。
这是我想说的非常重要的一点。 因为，很多人一听到 我推测很多现在活着的人将会活到一千或更多年以上， 他们都在想，哦，我们将会在这几十年内发明 延缓老化的治疗方法， 研究如何活到一千年甚至更多的治疗方法。 我并不是这么说。 我说的只是这些延长寿命的治疗方法的 发展速度会足够使人们继续活下去。 这些治疗方法我想永远都不可能完美， 但我们将可以在还没有两百岁的人之前就研究到如何治疗两百岁的人所死于的病理因素。 接下来，我们就在还没有三，四百岁的人之前就研究到如何治疗三，四百岁的人所死于的因素。 我称这为“长寿逃逸速度”， 要逃离死亡，长寿治疗方法必有快速的发展，叫逃逸速度。 （笑声） 这是个很容易明白的名称。
这就是我们可以期待 在余下的预期寿命， 以他们的健康来衡量， 到了一定年龄，相对应的治疗就相应而出。 如果你已经100岁，或者你是80岁， 平均80岁， 我们可能很难为您做些什么， 因为您的时间不多了。 所以最初的，实验性疗法对你已经不起作用了。 你将无法避免老化。 可是，如果您才五十岁的话， 您很有可能像我刚刚描述的那个样子摆脱了老化去世的问题。 （笑声） 您不但可以活的更久些， 某种意义上 你的青春，从身体和头脑上， 你的生命变得更加年轻， 你死于和老化有关的病症的几率也会降低。 当然，如果你还不到五十岁的话， 您更有可能永远摆脱了老化去世的问题， 而不会虚弱因老化而生成的疾病死亡。
因此，这是我得到的一个真正的结论，就是说第一位[能够活到一百五十岁 – 我们不知道该人现在多老了， 因为我们不知道第一代[延长寿命的] 疗法要多久才会出现。 但无论是年龄， 我声称的第一人会活到一千年的人 – 当然，排除全球性灾难 - 实际上， 大概只有比我说的那位活到一百五十岁的人年轻十岁左右。 很令人值得想一想的结论吧。
好，接下来我要用这个讲座所剩下的时间， 我的七个半分钟来谈谈我所谓的第一个步骤， 就是我们如何得到这第一批延长寿命的适中治疗， 使我们可以达到长寿逃逸速度？ 而为了做到这一点，我需要说一点点关于老鼠的事。 我有一个对强健人类再生相应的里程碑， 我不是很富有想象力地称它为强健老鼠再生[的治疗科技]。 这是什么呢？ 就是我们要采用一种长寿的老鼠， 就等于平均可以活三年左右的老鼠。 我们完全没有碰过它们，直到它们已经两岁。 然后我们对它们做了一大堆的东西， 用那些治疗方法使它们延长寿命， 想办法让他们平均活到五岁。 因此，换句话说，我们开始把这些老鼠治疗后，添加了两年寿命 – 已经是它们剩余寿命 的三倍。
接下来的问题是，到底什么时候， 我们讨论的这些才能用在人类身上呢？ 我们现在可以，正如我已经解释过， 把它称为强健人类再生，或长寿逃逸速度。 第二，从我们得到的第一只老鼠时开始， 公众对多久我们才能获得这些东西， 对这些科技的发展有什么影响？ 第三，问题是，它对多少人想要避免老化的人们起作用？ 这些科技有什么影响呢？ 我的看法是， 第一个问题完全是生物学的问题， 这是非常难回答。 一个人必须非常投机， 和我的许多同事会说，我们不应该做这种推测， 我们应该简单地保持沉默，直到我们了解更多。
我觉得这是一派胡言。 保持沉默，绝对是不负责任的。 我们需要给我们最好的猜测有时间框架， 以便使人们有个概念， 使他们能够评估他们的优先事项。 所以，我说，从我们应用强健老鼠再生的科技 的十五年内，我们有百分之五十的机会 实现强健人类再生科技 这个重要的里程碑。 强健老鼠再生的科技应用的十五年内， 人们的看法可能会变好。 因为人们往往低估的科学进步的困难性。 因此，他们很可能会认为只需五年。 他们可能是错误的，但实际上这不太重要。 最后，当然，我认为公众对于老龄化 的看法这么的矛盾的主要原因， 是我刚才谈到的全球恍惚的应对策略。 这将是历史性的一刻， 因为公众将不再认为老化是人类不可避免的， 因为它已经非常有效地在小老鼠体内被推迟。 因此，我们很可能会看到人们的观念有了巨大变化， 而这将会具有极大的影响。
为了现在要告诉你我们要如何得到这些老鼠， 我要补充一点我对老化的描述。 我会用“损害”这个词来表示 所有由新陈代谢中阶段造成的东西， 而最终导致不可避免的死亡。 因为这个关键的是， 尽管这些损害只有在最终才会造成不可避免的死亡， 它们是从我们出生之前就开始累积的东西，我们整个人生它们都不断累积。 但是这些损害不是新陈代谢的一部分， 这一点对我们来说是有益的。 因为这样我们可以重新绘制我们的原始图。 我们可以说，老年学和老年病学之间根本区别就是， 老年学试图抑制[避免]新陈代谢[的副作用]， 这些“损害”累积的速度。 我等一下会准确地解释我所谓 的“损害”在生物学里指的是什么。 老年病学呢，就试图阻止[医治] 这些“损害”所带来的的后果， 比如说死亡。这是一个败仗， 因为损害只会继续积累。
如果我们这样看的话，有第三种办法。 我们可以把它叫做工程方法， 我声称工程方法是在人类的科技，技术范围之内。 该工程方法不会干预任何[我们身体内的新陈代谢的]过程。 它不会干预这个过程，也不干预这一个。 这很好，因为这意味着这不是一个败仗， 并且它是在我们现在的[技术]范围之内能够做到的事情， 因为它不涉及对人类进化改善。 该工程方法只是表示， “我们定期修复所有的这些不同类型的损害 – 他们不一定完全修复[这些损害]， 但修复的足以让我们继续避免 一个会造成导致死亡或生病的程度。” 我们知道这个门槛程度的存在， 因为我们只有当我们在中年时才会得到与年龄有关的疾病， 即使损害已经从我们诞生时就开始累积了。
为什么我说，[工程方法]在人类近期的技术范围内呢？这[图片]基本上就是原因。 这图片的重点在底部。 如果我们试图说新陈代谢的那个部分才是对老化过程有着重要的影响， 那我们可能要在这里呆一整晚， 因为基本上新陈代谢的每个组件都对老化有影响。 这个列表仅仅是一个例子，它是不完整的。 右边的列表也一样不完整。 它们只是一种与年龄 有关的病的列表。 但这中间的我主张是完整的列表， 所有代谢副作用有资格被称为“损害”， 最终会导致病理[不可避免的死亡] 或可能造成病理类型。 而这列表只有七个。 当然，这七个是类别，但只有七个。 细胞损失，染色体突变，在线粒体基因突变等。
首先，我想给你们解释一个为什么我认为这份列表是完全的。 当然，我们可以使用生物学的角度来争论。 可以说，好，我们是什么做的？ 我们是由细胞和细胞间的东西。 “损害”可以累积在那里？ 答案是，长期存在的分子里， 因为如果一个短暂寿命的分子遭到破坏，它将会在寿命完了后被销毁 – 就像蛋白质被水解摧毁 – 累积的损害也一起被销毁了。 所以“损害”累积的地方一定是很长寿命的分子里。 因此[因为这个理由的很大的可能性]，这七个东西，都是由老年学士很久以前就讨论过了。 这是相当好的消息，因为这意味着， 尽管我们在这二十年里对生物学有着很大的成就， 这份列表还只有七样东西是一个非常好的迹象， 因为它显示它已不可再增加了。 这个消息比你们想象的更好， 因为我们在原则上知道如何在老鼠里解决所有这些七样东西 – 我所谓的原则指的是， 我们或许可以真正实现在十年内这些修复治疗。 其中有些[七样里的]部分已经落实了，尤其是在顶部的。
我[在这里]没有时间一个一个的解释， 但我的结论是，如果我们能够得到适合的资金， 那么我们或许可以在只有十年内成功发展强健的大规模人类再生[治疗科技]， 但我们确实需要认真想想它。 我们需要真正开始尝试。 对于观众里的生物学家， 你们可能有一些问题，我会回答你们。 你可能对这个讲座有些不满， 但你必须去阅读这些[已经刊登在研究杂志]内容， 我已经刊登了对老化很多的资料； 而且我就凭着这些研究为基础对人类老化治疗科技持乐观态度， 里头的细节还有很多。 这些细节使我对我在这里预测的 相当挑战性的时间表更加有信心。 如果你觉得我错了， 我希望你能看了这些资料以及研究报考后再来解释为什么你认为我是错的。
最主要的是你不应该相信 自称是老年医学的人， 因为在任何领域里 如果有激进的思想变化，主流的人一定有点抵抗 而且不认真的对待它。 所以，你必须真正做好准备工作， 才能了解这是否属实。
我们在结束前就讲讲几件事。 有一件事就是，你将会在下届会议听一个家伙说起以前， 当他说他可以测序人类基因组时，人们是怎么的回答他。 每个人都说：“这是不可能的。” 可是你也知道， 这确实发生了。 我们有不同的策略 – 有玛士撒拉奖， 这基本上是一个鼓励创新， 做你认为是可行的[方法延长寿命]， 如果成功的话，你就可以赢钱。 还有一个计划建议组织一个机构， 可是这将会需要点钱。 我的意思是，你看我们在伊拉克战争上耗这么久浪费了多少钱？ 不会再久吧。好吧。 （众笑） 这些研究的钱的来源最好是[私人]慈善，因为利润会分散生物技术研究公司[的注意力]， 但我认为它[我所提出的这些时间表和延长人类寿命的治疗科技的发展蓝图]]基本上有着百分之九十的机会成功。 因为我们已经知道应该怎么做。我就说到这里。 谢谢您。
（鼓掌）
克里斯安德森：好。我不知道大家有没有问题， 但我想我会给他们机会。 观众：既然你在谈论老龄化，并试图战胜它， 那为什么你看上去就像一位老人呢？
（众笑）
奥布里德格雷：因为我是一个老人。其实我是已经是一百五十八岁。
（众笑）
（鼓掌）
观众：这个星球上的物种进化了免疫系统， 以对抗各种的疾病，使个人活到足够生育的年龄。 不过，据我所知，所有的物种都进化到实际会死亡， 因此，当细胞分裂时，端粒酶变得越来越短了，最终物种死亡。 那么，为什么进化过程似乎已选定‘针对’永存不朽？ 或者那只是进化过程还不完整？
奥布里德格雷：好！谢谢你问一个我可以 用一个没有争议的答案来回答你。 我要告诉你主流思想的答案来回答你的问题， 我也恰巧同意这个答案。 那就是，不，老化不是一个进化过程的后果， 只是进化过程所忽视的后果。 换句话说，我们会老化，因为没有老化的话比较难； [因为]你需要更多的遗传途径，你的基因需要变得更复杂， 以便让你老的比较慢些， 而且你越想要把老化推迟，你[的身体的进化过程]就越需要面对这些难题。 因此，到进化不重要的程度， 不在乎是个体， 或则生活的很长的一段时间， 或则靠生育种种方法来把基因传给下一代，有一定的调节， 这就是为什么不同物种有不同的寿命， 但是这就是为什么没有永存的物种。
克里斯安德森：这些基因并不关心，但我们关心？
奥布里德格雷：是的。
观众：您好。我听说在过去的二十年中， 基本上这个星球上的人的平均寿命增长了十年。 如果以这个资料推断，如果我没有在我的摩托车上发生任何事故， 我将能够活到一百二十岁。 这意味着，我将会变成你所谓能够活到一千年研究课题之一？
奥布里德格雷：如果你瘦一点儿。
（众笑） 你的数据有点出入。 标准的数字是， 寿命已经在每十年增长一至两年。 因此，它不是你觉得或希望的那么好。 不过，我打算尽快将它快速发展到每年寿命多一年。
观众：我被告知，许多我们成人的脑细胞， 实际上在胚胎里是就有了， 而脑细胞能活八十年左右的时间。 如果事实的确如此， 在生理的角度看，对再生[科技]的世界会有什么影响？ 如果在我身体的所有细胞， 可以活到八十年，而不是一个典型的在两个月就死去的细胞？
奥布里德格雷：当然，这是技术问题。 基本上我们需要做的是取代大脑 的几个领域的细胞的流失率， 尤其是神经元，但我们不想比 那流失率更快地取代任何细胞 – 因为更换地太快会降低认知功能。 我刚刚说的没有不老化物种 是有点过于简单化。 有些物种没有老化。例如水螅 – 因为他们没有一个神经系统 – 也没有任何用于老化的的细胞 却有长寿的细胞组织。

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Aubrey de Grey says we can avoid aging
18 minutes is an absolutely brutal time limit, so I'm going to dive straight in, right at the point where I get this thing to work. Here we go. I'm going to talk about five different things. I'm going to talk about why defeating aging is desirable. I'm going to talk about why we have to get our shit together, and actually talk about this a bit more than we do. I'm going to talk about feasibility as well, of course. I'm going to talk about why we are so fatalistic about doing anything about aging. And then I'm going spend perhaps the second half of the talk talking about, you know, how we might actually be able to prove that fatalism is wrong, namely, by actually doing something about it.

I'm going to do that in two steps. The first one I'm going to talk about is how to get from a relatively modest amount of life extension -- which I'm going to define as 30 years, applied to people who are already in middle-age when you start -- to a point which can genuinely be called defeating aging. Namely, essentially an elimination of the relationship between how old you are, and how likely you are to die in the next year -- or indeed, to get sick in the first place. And of course, the last thing I'm going to talk about is how to reach that intermediate step, that point of maybe 30 years life extension.

So I'm going to start with why we should. Now, I want to ask a question. Hands up: Anyone in the audience who is in favor of malaria? That was easy. OK. OK. Hands up, anyone in the audience who's not sure whether malaria is a good thing or a bad thing? OK. So we all think malaria is a bad thing. That's very good news, because I thought that was what the answer would be. Now the thing is, I would like to put it to you that the main reason why we think that malaria is a bad thing is because of a characteristic of malaria that it shares with aging. And here is that characteristic. The only real difference is that aging kills considerably more people than malaria does.

Now, I like in an audience, in Britain especially, to talk about the comparison with fox-hunting, which is something that was banned after a long struggle, by the government not very many months ago. I mean, I know I'm with a sympathetic audience here, but, as we know, a lot of people are not entirely persuaded by this logic. And this is actually a rather good comparison, it seems to me. You know, a lot of people said, "Well, you know, city boys have no business telling us rural types what to do with our time. It's a traditional part of the way of life, and we should be allowed to carry on doing it. It's ecologically sound; it stops the population explosion of foxes." But ultimately, the government prevailed in the end, because the majority of the British public, and certainly the majority of members of Parliament, came to the conclusion that it was really something that should not be tolerated in a civilized society.

And I think that human aging shares all of these characteristics in spades. What part of this do people not understand? It's not just about life, of course -- (Laughter) it's about healthy life, you know -- getting frail and miserable and dependent is no fun, whether or not dying may be fun. So really, this is how I would like to describe it. It's a global trance. These are the sorts of unbelievable excuses that people give for aging. And, I mean, OK, I'm not actually saying that these excuses are completely valueless. There are some good points to be made here. Things that we ought to be thinking about, forward planning so that nothing goes too -- well, so that we minimize the turbulence when we actually figure out how to fix aging.

But these are completely crazy, when you actually remember your sense of proportion. You know, these are arguments, these are things that would be legitimate to be concerned about. But the question is, are they so dangerous -- these risks of doing something about aging -- that they outweigh the downside of doing the opposite, namely, leaving aging as it is? Are these so bad that they outweigh condemning 100,000 people a day to an unnecessarily early death. You know, if you haven't got an argument that's that strong, then just don't waste my time, is what I say. (Laughter)

Now, there is one argument that some people do think really is that strong, and here it is. People worry about overpopulation; they say, "Well, if we fix aging, no one's going to die to speak of, or at least the death toll is going to be much lower, only from crossing St. Giles carelessly. And therefore, we're not going to be able to have many kids, and kids are really important to most people." And that's true. And you know, a lot of people try to fudge this question, and give answers like this. I don't agree with those answers. I think they basically don't work. I think it's true, that we will face a dilemma in this respect. We will have to decide whether to have a low birth rate, or a high death rate. A high death rate will, of course, arise from simply rejecting these therapies, in favor of carrying on having a lot of kids.

And, I say that that's fine -- the future of humanity is entitled to make that choice. What's not fine is for us to make that choice on behalf of the future. If we vacillate, hesitate, and do not actually develop these therapies, then we are condemning a whole cohort of people -- who would have been young enough and healthy enough to benefit from those therapies but will not be, because we haven't developed them as quickly as we could -- we'll be denying those people an indefinite life span, and I consider that that is immoral. That's my answer to the overpopulation question.

Right. So the next thing is, now why should we get a little bit more active on this? And the fundamental answer is that the pro-aging trance is not as dumb as it looks. It's actually a sensible way of coping with the inevitability of aging. Aging is ghastly, but it's inevitable, so, you know, we've got to find some way to put it out of our minds, and it's rational to do anything that we might want to do, to do that. Like, for example, making up these ridiculous reasons why aging is actually a good thing after all. But of course, that only works when we have both of these components. And as soon as the inevitability bit becomes a little bit unclear -- and we might be in range of doing something about aging -- this becomes part of the problem. This pro-aging trance is what stops us from agitating about these things. And that's why we have to really talk about this a lot -- evangelize, I will go so far as to say, quite a lot -- in order to get people's attention, and make people realize that they are in a trance in this regard. So that's all I'm going to say about that.

I'm now going to talk about feasibility. And the fundamental reason, I think, why we feel that aging is inevitable is summed up in a definition of aging that I'm giving here. A very simple definition. Aging is a side effect of being alive in the first place, which is to say, metabolism. This is not a completely tautological statement; it's a reasonable statement. Aging is basically a process that happens to inanimate objects like cars, and it also happens to us, despite the fact that we have a lot of clever self-repair mechanisms, because those self-repair mechanisms are not perfect.

So basically, metabolism, which is defined as basically everything that keeps us alive from one day to the next, has side effects. Those side effects accumulate and eventually cause pathology. That's a fine definition. So we can put it this way: we can say that, you know, we have this chain of events. And there are really two games in town, according to most people, with regard to postponing aging. They're what I'm calling here the gerontology approach and the geriatrics approach. The geriatrician will intervene late in the day, when pathology is becoming evident, and the geriatrician will try and hold back the sands of time, and stop the accumulation of side effects from causing the pathology quite so soon. Of course, it's a very short-termist strategy, it's a losing battle, because the things that are causing the pathology are becoming more abundant as time goes on.

The gerontology approach looks much more promising on the surface, because, you know, prevention is better than cure. But unfortunately the thing is that we don't understand metabolism very well. In fact, we have a pitifully poor understanding of how organisms work -- even cells we're not really too good on yet. We've discovered things like, for example, RNA interference only a few years ago, and this is a really fundamental component of how cells work. Basically, gerontology is a fine approach in the end, but it is not an approach whose time has come when we're talking about intervention. So then, what do we do about that? I mean, that's a fine logic, that sounds pretty convincing, pretty iron-clad, doesn't it?

But it isn't. Before I tell you why it isn't, I'm going to go a little bit into what I'm calling step two. Just suppose, as I said, that we do acquire -- let's say we do it today for sake of argument -- the ability to confer 30 extra years of healthy life on people who are already in middle age, let's say 55. I'm going to call that robust human rejuvenation. OK. What would that actually mean for how long people of various ages today -- or equivalently, of various ages at the time that these therapies arrive -- would actually live? In order to answer that question -- you might think it's simple, but it's not simple. We can't just say, "Well, if they're young enough to benefit from these therapies, then they'll live 30 years longer." That's the wrong answer. And the reason it's the wrong answer is because of progress.

There are two sorts of technological progress really, for this purpose. There are fundamental, major breakthroughs, and there are incremental refinements of those breakthroughs. Now, they differ a great deal in terms of the predictability of time frames. Fundamental breakthroughs: very hard to predict how long it's going to take to make a fundamental breakthrough. It was a very long time ago that we decided that flying would be fun, and it took us until 1903 to actually work out how to do it. But after that, things were pretty steady and pretty uniform. I think this is a reasonable sequence of events that happened in the progression of the technology of powered flight. We can think, really, that each one is sort of beyond the imagination of the inventor of the previous one, if you like. The incremental advances have added up to something which is not incremental anymore.

This is the sort of thing you see after a fundamental breakthrough. And you see it in all sorts of technologies. Computers, you can look at a more or less parallel time line, happening of course a bit later. You can look at medical care. I mean, hygiene, vaccines, antibiotics -- you know, the same sort of time frame. So I think that actually step two, that I called a step a moment ago, isn't a step at all. That in fact, the people who are young enough to benefit from these first therapies that give this moderate amount of life extension, even though those people are already middle-aged when the therapies arrive, will be at some sort of cusp. They will mostly survive long enough to receive improved treatments that will give them a further 30 or maybe 50 years. In other words, they will be staying ahead of the game. The therapies will be improving faster than the remaining imperfections in the therapies are catching up with us.

This is a very important point for me to get across. Because, you know, most people, when they hear that I predict that a lot of people alive today are going to live to 1,000 or more, they think that I'm saying that we're going to invent therapies in the next few decades that are so thoroughly eliminating aging that those therapies will let us live to 1,000 or more. I'm not saying that at all. I'm saying that the rate of improvement of those therapies will be enough. They'll never be perfect, but we'll be able to fix the things that 200-year-olds die of, before we have any 200-year-olds. And the same for three- and 400 and so on. I decided to give this a little name, which is "longevity escape velocity." (Laughter) Well, it seems to get the point across.

So, these trajectories here are basically how we would expect people to live, in terms of remaining life expectancy, as measured by their health, for given ages that they were at the time that these therapies arrive. If you're already 100, or even if you're 80 -- and an average 80-year-old, we probably can't do a lot for you with these therapies, because you're too close to death's door for the really initial, experimental therapies to be good enough for you. You won't be able to withstand them. But if you're only 50, then there's a chance that you might be able to pull out of the dive and, you know -- (Laughter) eventually get through this and start becoming biologically younger in a meaningful sense, in terms of your youthfulness, both physical and mental, and in terms of your risk of death from age-related causes. And of course, if you're a bit younger than that, then you're never really even going to get near to being fragile enough to die of age-related causes.

So this is a genuine conclusion that I come to, that the first 150-year old -- we don't know how old that person is today, because we don't know how long it's going to take to get these first-generation therapies. But irrespective of that age, I'm claiming that the first person to live to 1,000 -- subject of course, to, you know, global catastrophes -- is actually, probably, only about 10 years younger than the first 150-year old. And that's quite a thought.

All right, so finally I'm going to spend the rest of the talk, my last seven and a half minutes, on step one; namely, how do we actually get to this moderate amount of life extension that will allow us to get to escape velocity? And in order to do that, I need to talk about mice a little bit. I have a corresponding milestone to robust human rejuvenation. I'm calling it robust mouse rejuvenation, not very imaginatively. And this is what it is. I say we're going to take a long-lived strain of mouse, which basically means mice that live about three years on average. We do exactly nothing to them until they're already two years old. And then we do a whole bunch of stuff to them, and with those therapies, we get them to live, on average, to their fifth birthday. So, in other words, we add two years -- we treble their remaining lifespan, starting from the point that we started the therapies.

The question then is, what would that actually mean for the time frame until we get to the milestone I talked about earlier for humans? Which we can now, as I've explained, equivalently call either robust human rejuvenation, or longevity escape velocity. Secondly, what does it mean for the public's perception of how long it's going to take for us to get to those things, starting from the time we get the mice? And thirdly, the question is, what will it do to actually how much people want it? And it seems to me that the first question is entirely a biology question, and it's extremely hard to answer. One has to be very speculative, and many of my colleagues would say that we should not do this speculation, that we should simply keep our counsel until we know more.

I say that's nonsense. I say we absolutely are irresponsible if we stay silent on this. We need to give our best guess as to the time frame, in order to give people a sense of proportion so that they can assess their priorities. So, I say that we have a 50/50 chance of reaching this RHR milestone, robust human rejuvenation, within 15 years from the point that we get to robust mouse rejuvenation. 15 years from the robust mouse. The public's perception will probably be somewhat better than that. The public tend to underestimate how difficult scientific things are. So they'll probably think it's five years away. They'll be wrong, but that actually won't matter too much. And finally, of course, I think it's fair to say that a large part of the reason why the public is so ambivalent about aging now is the global trance I spoke about earlier, the coping strategy. That will be history at this point, because it will no longer be possible to believe that aging is inevitable in humans, since it's been postponed so very effectively in mice. So we're likely to end up with a very strong change in people's attitudes, and of course that has enormous implications.

So in order to tell you now how we're going to get these mice, I'm going to add a little bit to my description of aging. I'm going to use this word "damage" to denote these intermediate things that are caused by metabolism, and that eventually cause pathology. Because the critical thing about this is that even though the damage only eventually causes pathology, the damage itself is caused ongoingly throughout life, starting before we're born. But it is not part of metabolism itself. And this turns out to be useful. Because we can re-draw our original diagram this way. We can say that, fundamentally, the difference between gerontology and geriatrics is that gerontology tries to inhibit the rate at which metabolism lays down this damage. And I'm going to explain exactly what damage is in concrete biological terms in a moment. And geriatricians try to hold back the sands of time by stopping the damage converting into pathology. And the reason it's a losing battle is because the damage is continuing to accumulate.

So there's a third approach, if we look at it this way. We can call it the engineering approach, and I claim that the engineering approach is within range. The engineering approach does not intervene in any processes. It does not intervene in this process, or this one. And that's good because it means that it's not a losing battle, and it's something that we are within range of being able to do, because it doesn't involve improving on evolution. The engineering approach simply says, "Let's go and periodically repair all of these various types of damage -- not necessarily repair them completely, but repair them quite a lot, so that we keep the level of damage down below the threshold that must exist, that causes it to be pathogenic." We know that this threshold exists, because we don't get age-related diseases until we're in middle age, even though the damage has been accumulating since before we were born.

Why do I say that we're in range? Well, this is basically it. The point about this slide is actually the bottom. If we try to say which bits of metabolism are important for aging, we will be here all night, because basically all of metabolism is important for aging in one way or another. This list is just for illustration, it is incomplete. The list on the right is also incomplete. It's a list of types of pathology that are age-related, and it's just an incomplete list. But I would like to claim to you that this list in the middle is actually complete, this is the list of types of thing that qualify as damage, side effects of metabolism that cause pathology in the end, or that might cause pathology. And there are only seven of them. They're categories of thing, of course, but there's only seven of them. Cell loss, mutations in chromosomes, mutations in the mitochondria and so on.

First of all, I'd like to give you an argument for why that list is complete. Of course one can make a biological argument. One can say, "OK, what are we made of?" We're made of cells and stuff between cells. What can damage accumulate in? The answer is, long-lived molecules, because if a short-lived molecule undergoes damage, but then the molecule is destroyed -- like by a protein being destroyed by proteolysis -- then the damage is gone, too. It's got to be long-lived molecules. So, these seven things were all under discussion in gerontology a long time ago and that is pretty good news, because it means that, you know, we've come a long way in biology in these 20 years, so the fact that we haven't extended this list is a pretty good indication that there's no extension to be done. However, it's better than that; we actually know how to fix them all in mice, in principle -- and what I mean by in principle is, we probably can actually implement these fixes within a decade. Some of them are partially implemented already, the ones at the top.

I haven't got time to go through them at all, but my conclusion is that, if we can actually get suitable funding for this, then we can probably develop robust mouse rejuvenation in only 10 years, but we do need to get serious about it. We do need to really start trying. So of course, there are some biologists in the audience, and I want to give some answers to some of the questions that you may have. You may have been dissatisfied with this talk, but fundamentally you have to go and read this stuff. I've published a great deal on this; I cite the experimental work on which my optimism is based, and there's quite a lot of detail there. The detail is what makes me confident of my rather aggressive time frames that I'm predicting here. So if you think that I'm wrong, you'd better damn well go and find out why you think I'm wrong.

And of course the main thing is that you shouldn't trust people who call themselves gerontologists because, as with any radical departure from previous thinking within a particular field, you know, you expect people in the mainstream to be a bit resistant and not really to take it seriously. So, you know, you've got to actually do your homework, in order to understand whether this is true.

And we'll just end with a few things. One thing is, you know, you'll be hearing from a guy in the next session who said some time ago that he could sequence the human genome in no time, and everyone said, "Well, it's obviously impossible." And you know what happened. So, you know, this does happen. We have various strategies -- there's the Methuselah Mouse Prize, which is basically an incentive to innovate, and to do what you think is going to work, and you get money for it if you win. There's a proposal to actually put together an institute. This is what's going to take a bit of money. But, I mean, look -- how long does it take to spend that on the war in Iraq? Not very long. OK. (Laughter) It's got to be philanthropic, because profits distract biotech, but it's basically got a 90 percent chance, I think, of succeeding in this. And I think we know how to do it. And I'll stop there. Thank you. (Applause)

Chris Anderson: OK. I don't know if there's going to be any questions but I thought I would give people the chance. Audience: Since you've been talking about aging and trying to defeat it, why is it that you make yourself appear like an old man? (Laughter)

AG: Because I am an old man. I am actually 158. (Laughter) (Applause)

Audience: Species on this planet have evolved with immune systems, to fight off all the diseases so that individuals live long enough to procreate. However, as far as I know, all the species have evolved to actually die, so when cells divide, the telomerase get shorter, and eventually species die. So, why does -- evolution has -- seems to have selected against immortality, when it is so advantageous, or is evolution just incomplete?

AG: Brilliant. Thank you for asking a question that I can answer with an uncontroversial answer. I'm going to tell you the genuine mainstream answer to your question, which I happen to agree with, which is that, no, aging is not a product of selection, evolution; [aging] is simply a product of evolutionary neglect. In other words, we have aging because it's hard work not to have aging; you need more genetic pathway, more sophistication in your genes in order to age more slowly, and that carries on being true the longer you push it out. So, to the extent that evolution doesn't matter, doesn't care whether genes are passed on by individuals, living a long time or by procreation, there's a certain amount of modulation of that, which is why different species have different lifespans, but that's why there are no immortal species.

CA: The genes don't care but we do?

AG: That's right.

Audience: Hello. I read somewhere that in the last 20 years, the average lifespan of basically anyone on the planet has grown by 10 years. If I project that, that would make me think that I would live until 120 if I don't crash on my motorbike. That means that I'm one of your subjects to become a 1000 year old?

AG: If you lose a bit of weight. (Laughter) Your numbers are a bit out. The standard numbers are that lifespans have been growing at between one and two years per decade. So, it's not quite as good as you might think -- you might hope. But I intend to move it up to one year per year as soon as possible.

Audience: I was told that many of the brain cells we have as adults are actually in the human embryo, and that the brain cells last 80 years or so. If that is indeed true, biologically are there implications in the world of rejuvenation? If there are cells in my body that live all 80 years, as opposed to a typical, you know, couple of months?

AG: There are technical implications certainly. Basically what we need to do is replace cells in those few areas of the brain that lose cells at a respectable rate, especially neurons, but we don't want to replace them any faster than that -- or not much faster anyway, because replacing them too fast would degrade cognitive function. What I said about there being no non-aging species earlier on was a little bit of an oversimplification. There are species that have no aging -- Hydra for example -- but they do it by not having a nervous system -- and not having any tissues in fact that rely for their function on very long-lived cells.