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@Aubrey de Grey : 致力于通过损伤修复方法逆转衰老，这比减缓衰老更容易。我的研究团队正在进行一项包含一千只老鼠的实验，旨在通过结合四种不同的损伤修复干预措施，将中年老鼠的寿命延长整整一年，这在老鼠身上相当于人类的30年，远超通常能达到的四个月。这项研究采用先进的细胞和基因疗法，同时靶向多种与年龄相关的损伤。

预测在12到15年内，有50%的几率达到“寿命逃逸速度”，这将能够使60岁的人返老还童，在接下来的20年里保持年轻状态，在此期间，进一步的进步将使我们能够进行额外的返老还童周期，这可能会为今天许多活着的人创造无限的健康寿命。

在投资方面，沙特王室对HEvolution的巨额投资是一个巨大的惊喜，尽管其成果尚未完全显现。Calico的运作方式非常糟糕，缺乏将已验证的概念转化为产品的途径，因此它几乎没有成功的可能。我对Altos Labs抱有更高的期望，尽管其运作方式有些奇怪，但他们聘请了该领域的许多顶尖人才。Retro Biosciences可能是这些公司中最有希望的一家，因为它拥有合适的资金和领导者。

在监管方面，蒙大拿州扩展“尝试权”立法，允许任何人获得通过FDA安全试验的治疗方法，这将加速进步。Prospera等特别经济区为生物医学创新创造了一个有利的监管环境，它允许在更短的时间内进行更安全的医疗干预测试。这些发展将促使传统司法管辖区现代化其监管结构，以保持竞争力。

关于公众对预防性医学的怀疑，将衰老定义为一种疾病，这可能有助于克服公众对预防性医学的怀疑，并促进对衰老相关疾病的治疗。目前，最重要的是加快尚未存在但能延长寿命的技术的研发进程。

与Aubrey de Grey博士进行了一次关于衰老和长寿的对话，他认为，逆转衰老比减缓衰老更容易，这主要基于他的损伤修复方法。

损伤修复：一千只老鼠的实验

目前在LEV基金会领导着一项雄心勃勃的研究：一项包含一千只老鼠的实验。选择在老鼠中年期（相当于人类的45岁左右）开始干预，而非幼年期。实验中结合四种不同的损伤修复干预措施，目标是将老鼠的寿命延长整整一年——这相当于人类的30年，远超以往研究中通常能达到的四个月。这项研究并非依赖于传统的饮食调整，而是采用先进的细胞和基因疗法，同时靶向多种与年龄相关的损伤。

投资与创新：巨额资金涌入，但成效参差不齐

近年来，长寿研究领域的资金发生了翻天覆地的变化，数十亿美元的资金涌入。沙特王室对HEvolution的巨额投资（目标为每年十亿美元，持续20年）着实让人吃惊，尽管目前投资规模尚未达到预期，但其为该领域带来的影响不容小觑。

然而，并非所有投资都取得了成功。Google旗下的Calico公司就是一个令人沮丧的例子，其运作方式存在严重缺陷，缺乏将科学发现转化为实际产品的有效途径，几乎没有成功的可能。相比之下，对Altos Labs（贝佐斯投资）抱有更高的期望，尽管其运作方式略显神秘，但其汇聚了该领域的众多顶尖人才。而Sam Altman创立的Retro Biosciences则因其充足的资金和优秀的领导者而成为最具前景的公司之一。

监管创新：蒙大拿州的“尝试权”立法与Prospera经济区

监管创新是加速长寿研究进步的关键。蒙大拿州突破性的“尝试权”立法扩展，允许任何人获得通过FDA安全试验的治疗方法，这将极大地推动新疗法的应用。同时，位于洪都拉斯的Prospera等特别经济区，通过创建专门为生物医学创新设计的监管环境，显著缩短了新疗法测试的时间，并提高了安全性。这些发展将迫使全球范围内的传统监管机构现代化其结构，以保持竞争力。

公众认知与未来展望

公众对预防性医学的普遍怀疑是一个巨大的挑战。为了克服这一障碍，正在探索将衰老定义为一种疾病的新方法，这或许能改变公众的认知，并促进对衰老相关疾病的治疗。

目前，最重要的是加快尚未存在但能延长寿命的技术的研发进程。预测，在12到15年内，有50%的几率达到“寿命逃逸速度”。这意味着可以使60岁的人返老还童，并在接下来的20年里保持年轻状态，在此期间，进一步的进步将使我们能够进行额外的返老还童周期，这可能会为今天许多活着的人创造无限的健康寿命。

行动号召

虽然目前尚无针对人类的成熟疗法，但我们正在积极推进研究，期待在未来几年内取得突破性进展。 鼓励大家关注LEV基金会（levf.org）的最新研究进展，并积极参与到这场改变人类未来的事业中来。


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01:08 我正在进行一项包含一千只老鼠的实验，旨在通过结合四种不同的损伤修复干预措施，将中年老鼠的寿命延长整整一年，这在老鼠身上相当于人类的30年，远超通常能达到的四个月。

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01:34 我预测，在12到15年内，我们有50%的几率达到“寿命逃逸速度”，这将使我们能够使60岁的人返老还童，并在接下来的20年里保持年轻状态，在此期间，进一步的进步将使我们能够进行额外的返老还童周期，这可能会为今天许多活着的人创造无限的健康寿命。

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04:06 HEvolution的出现，即沙特王室承诺在20年内每年投入10亿美元用于寿命研究和开发，是整个行业中最大的惊喜之一。

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06:19 Calico（谷歌资助）的运作方式非常糟糕，缺乏将已验证的概念转化为产品的途径，因此它几乎没有成功的可能。

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07:43 我对Altos Labs（贝佐斯资助）抱有更高的期望，尽管其运作方式有些奇怪，但他们聘请了该领域的许多顶尖人才。

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08:38 Retro Biosciences（山姆·阿尔特曼的企业）可能是这些公司中最有希望的一家，因为它拥有合适的资金和领导者。

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08:56 Retro Biosciences的乐观前景主要基于其领导者的能力，而不是其采用的策略或方法。

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10:04 Zuzalu和Vitalia等活动旨在探索更有效的方式来促进社区建设、思想交流和相互教育，并已取得成功。

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11:44 Prospera（洪都拉斯的一个特别经济区）为生物医学创新创造了一个有利的监管环境，它允许在更短的时间内进行更安全的医疗干预测试。

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16:59 Prospera等特别经济区的成功将促使传统司法管辖区现代化其监管结构，以保持竞争力。

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17:17 蒙大拿州扩展“尝试权”立法，允许任何人获得通过FDA安全试验的治疗方法，这将加速进步。

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20:02 将衰老定义为一种疾病，这可能有助于克服公众对预防性医学的怀疑，并促进对衰老相关疾病的治疗。

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22:27 为了治疗衰老，逆转衰老可能比减缓衰老更容易，因为这更像是预防性维护，而不是让机器更清洁地运行。

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25:58 我的新组织LEV基金会正在进行一项大型实验，将四种不同的治疗方法结合起来，以同时对抗衰老相关的多种损伤。

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26:38 我们的实验从老鼠中年开始，目标是将它们的健康寿命延长一年，这将是该领域的一大突破。

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34:08 目前，最重要的是加快尚未存在但能延长寿命的技术的研发进程。

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36:56 我预测，在未来12到15年内，我们有50%的几率达到“寿命逃逸速度”，届时我们将能够显著延长人类的健康寿命。

00:00

Welcome back to the Health Longevity Secrets show with your host, Dr. Robert Lufkin. His book titled Lies I Taught in Medical School is a New York Times bestseller. See the show notes for a link to download a free chapter. And now please enjoy this week's episode as we speak about the future of aging with Dr. Aubrey de Grey. 语法解析

00:21

We hope you can join us this week where Dr. Aubrey de Grey reveals why reversing aging may be easier than slowing it down in this mind-expanding conversation that challenges conventional wisdom about human longevity. The renowned biomedical gerontologist outlines his damage repair approach that's gaining mainstream scientific acceptance after initial skepticism. 语法解析

00:45

At the LEV Foundation, Dr. DeGray is conducting a thousand mouse study, combining four different damage repair interventions in middle-aged mice. And he's aiming for a full year of life extension, which in mouse terms is about 30 years in human terms, which is far beyond the four months normally achieved. 语法解析

01:08

Unlike conventional approaches that rely on dietary modifications, this ambitious project incorporates advanced cell and gene therapies that target multiple forms of age-related damage simultaneously. Now, looking forward, Dr. DeGray offers his characteristic probabilistic prediction, which is a 50-50 chance of reaching, quote, longevity escape velocity, unquote, within 12 to 15 years. 语法解析

01:34

This would enable taking 60-year-olds and rejuvenating them enough that they would be biologically 60 again for another 20 years, during which time further advances would enable additional rejuvenation cycles, potentially creating open-ended healthy lifespans for many alive today. 语法解析

01:57

This episode is brought to you by El Nutra, maker of the Prolonged Fasting Mimicking Diet. If you'd like to try it, use the link in the show notes for 20% off. What's the best imaging test to assess health and longevity? I used to think it was the CT coronary artery calcium score. Well, I don't anymore because now with the same x-ray exposure and time as a calcium score, I can get a complete metabolic heart scan. 语法解析

02:26

This includes not only the CT calcium score, but also calculated arterial age, liver fat quantification, and CT bone mineral density. These key metabolic and cardiovascular markers can detect the actual disease that blood or genetic testing only show the risk for. 语法解析

02:45

This scan is available anywhere in the U.S. without a doctor's prescription. See the attached link and use the code LufkinCT for $100 off. Join the health longevity medical imaging revolution today. And now, please enjoy this week's episode. Hey, Aubrey, thanks for coming on the show. Well, thank you for having me, Robert. 语法解析

03:11

It's so great to talk with you as an expert in longevity, especially with all the early stage research you're doing. I love it. Well, maybe just start off. We're undergoing a revolution in longevity knowledge and things are moving faster than have ever occurred before in longevity. What are the most exciting things that you've seen maybe in the last five years you think that really surprised you? 语法解析

03:41

Wow, I mean there are surprises coming along all the time and they're pretty much all good surprises I guess the single biggest surprise in the entire industry was the arrival of evolution in other words the commitment by the Saudi royal family to put ideally a billion dollars per year for 20 years into longevity research and development that 语法解析

04:06

has taken a little longer than we were hoping to actually bear fruit. They're certainly not spending anywhere near a billion dollars a year yet, but they have put the right kind of groundwork together. They've certainly got an extremely appropriate person running the show, Mehmood Khan. 语法解析

04:24

And they've had extremely good top management as well. People that I know who are, you know, I really trust to get things right. So that's definitely even though it hasn't really borne full fruit yet, it's definitely a huge thing. And it was a very big surprise. 语法解析

04:40

Quick question on evolution, just excuse me for interrupting you, but in evolution, it seems to follow along several other big companies in that space or big projects with, you know, Calico initially with Google and then, you know, Altos with a number of funders, including Jeff Bezos and now evolution. How do these three companies differ and what are their, how are their approaches different? Yeah. 语法解析

05:07

Right. So actually, yeah, I was going to go to that because, as you say, these companies are, if not as big as evolution in terms of dollars, they are within range. They were not quite such surprises to me because I was aware a long time earlier that both the Google twins, in the case of Calico and Bezos, had considerable interest in this space. 语法解析

05:35

and indeed it was highly frustrating to me that they hadn't actually helped philanthropically at all but they're just the kinds of people who don't really believe in non-profits doing good work in technology I guess and 语法解析

05:51

and eventually they decided to do something that was nominally for profit, though of course they don't actually need to make money out of these things. Calico, to be perfectly honest, has been an absolute disaster. It has been put together in a very inferior way such that it doesn't really have a pipeline. It doesn't really have any way to take proven concepts and turn them into products. It's got… 语法解析

06:19

like the curiosity-driven basic science very well nailed down in terms of the quality of personnel. And it's also got the actual business end, the kind of Genentech Mark II run by obviously the person who used to run Genentech, but it doesn't have anything in the middle linking the two. And so it'll be complete luck if it ever does anything useful. It's an absolute tragedy. 语法解析

06:46

Altos, I have considerably higher hopes for. Bezos started talking to me back in 2006 about aging. Again, never gave us any money, but… 语法解析

07:00

but did eventually decide to put proper money into this area. The good news with Altos is that they hired a lot of the top people in the field, which means that no one school of thought is going to dominate what goes on there. You know, the whole way it's being done is a little curious. You know, Bezos never talks about it. It's kind of only kind of half-cultured. 语法解析

07:26

announced that he is even the main funder. And they are not allowed to describe themselves as a longevity company. It's a little weird. But I do have faith that they're going to do good work. 语法解析

07:43

Then there are, of course, other ones. So a lot of the people in crypto, the big hitters in crypto have been getting into this. And some of them have been helpful philanthropically. Vitalik Buterin is well known as one of the people who have given me and my various organizations quite a lot of money over the years. Brian Armstrong, who created Coinbase, has created a company again, New Limit, very heavily funded. 语法解析

08:09

And then, of course, there's Retro, which is probably the single most promising of these companies because Sam Altman decided to throw proper money at this thing, a couple of hundred million, and he did it right. He actually found a proper longevity crusader to go and run the thing, Joe Betz-Lacroix, who's a great friend of mine, and I have very high hopes that Retro will achieve great things. 语法解析

08:38

And the optimism for retro versus these other companies is based on the leadership of this individual, or is there some strategy they're using that's different or some particular approach to longevity that they're taking? It's mostly the leadership. 语法解析

08:56

Essentially, Joe is the kind of person who actually understands the goal, thinks like an engineer, thinks like me. So he's going to get things right. 语法解析

09:08

Yeah, that makes sense. And well, on this topic, before we can get back into the longevity things, but on this topic, you mentioned Vitalik Buterin, and we were talking off camera a little bit about your experience with, 语法解析

09:25

down in Prospera, that community in Honduras, which just had a wonderful conference. I think you were at there. Maybe you could tell our audience a little bit about this and why you're so excited about it. 语法解析

09:40

So this all started several months ago with the creation of a remarkable event in Montenegro called Zuzalu. And this was essentially conceived and bankrolled by Vitalik Vissarion. Essentially, he was able to bring together a couple of hundred people for a couple of months. I only attended one week of it. But, of course, quite a lot of people attended most of the event. 语法解析

10:04

And the idea of it was to essentially explore whether something that could, something that was longer than a conference, but, you know, still had a couple of hundred people, could do things that no classical format could do. Essentially, if it could, you know, 语法解析

10:28

be more effective at community building, at bringing ideas together, mutual education and so on. And it was very successful. So the whole idea has very much become a kind of a program to do such events all over the world in various places and in various ways. 语法解析

10:57

And the second one, which is called Vitalia, happened. Well, it's happening right now. In fact, it started on, I think, January the 6th. And it normally was going to go until March the 1st. They've actually extended it by another month. I was there for the first month. And it's really going to make a difference. 语法解析

11:17

The thing that distinguishes Vitalia from Zulu, the main thing, is that Vitalia is happening in Prospera. Prospera is a special economic zone in Honduras, not actually on the mainland. It's on an island called Roatan. So it's been set up to be, you know, to have everything that you might want in a special economic zone. It's very safe. It's like, you know, it's Western, really, in most ways. And… 语法解析

11:44

In particular, what they wanted to do is to emphasize biomedical innovation. So they've set themselves up legally in such a way as to really maximize the incentives for clinics and companies to incorporate or relocate there and to get stuff done that they would not be able to do in more traditional jurisdiction. 语法解析

12:12

in particular the regulatory structure, because they have very wide legal autonomy, not over criminal law or the military or anything, but they have basically everything else, they can put together their own regulatory structures. And they are showing very clearly that the safety that people need in the testing of new medical interventions 语法解析

12:37

can be achieved without any compromises in a tiny fraction of the time that it takes in the US, for example. And so, of course, this is rather attractive to rather a lot of people. I cannot speak too highly of these people. They are very, very competent. They have enormous energy. There's a lot of representation from the younger generation, shall we say. 语法解析

13:01

And, you know, they're getting things right. So I will go so far as to say that I think it's quite likely that within even a couple of years from now, Prospera will be the global hub for medical tourism. And it won't just be because of these events like Vitalia, but that's certainly giving the thing, you know, its original impetus. 语法解析

13:26

And the more this happens, the better, of course. So there are other similar events happening around the world that are planned for later this year, for next year. Actually, Vitalik himself is kind of taking a bit of a back seat. I understand that he did not provide financing for Vitalia and he didn't turn up either, whereas he very much did that for Zuzulu. 语法解析

13:52

Well, plenty of other luminaries did turn up, so I wasn't the only one. There's a huge emphasis on the concept of network states, so decentralized, legally autonomous entities. And the guru of that whole field, Balaji Srinivasan, also came along in person. 语法解析

14:11

Various other people have got involved, people who will raise the credibility and reputation of this whole enterprise. So I believe it's got what it needs to make a huge difference. And so Vitalia then will be an ongoing organization there. We'll continue on. It's just not a one-time conference, but it's sort of long-term. So Prospera is the name of the special economic zone. That is absolutely perfect. 语法解析

14:42

The TARIA, I think, is a kind of flexible concept. It was originally supposed to be this two-month thing ending on March 1st. They've already extended it. The companies, the entities that are… 语法解析

14:57

who either coming out of Vittalia or are being attracted to Prospera by Vittalia, these things will obviously in many cases be permanent as well. So it's kind of a little bit of a gray area whether you call Vittalia permanent or not. 语法解析

15:13

I see. Yeah. And well, you mentioned several other conferences, upcoming conferences around the world that you're excited about. Could you share some of those? Well, so let's not call them conferences. Because, I mean, it's a bit difficult to call something that's two months long a conference. What they're actually calling them is pop-up cities. 语法解析

15:32

But yeah, I mean, there are ones planned elsewhere in the world. There's one I know being planned in Africa, I think in Zanzibar. There's a couple of ideas for South America. Uruguay apparently has particularly friendly legislation when it comes to special economic zones. So there's a bunch of thought going on there. I'm not the expert there. You should really talk to the people who are involved. 语法解析

15:57

who are running this show in order to understand that. Yeah, yeah, we'll get some of them on here. But yeah, it's such an exciting area. So it sounds like you see development of biotech projects 语法解析

16:14

In this case, sort of without the bureaucratic over scrutiny or the weight of the FDA on it that slows things down and many people think unnecessary in many cases. And I think I want to emphasize that this is really the most important thing is in the near term, in a small number of years, because… 语法解析

16:40

To the extent that this succeeds, it will create a huge amount of FOMO. There will be enormous incentives for traditional jurisdictions, whether the US or elsewhere, to actually get on with modernizing their regulatory structures so as to compete with structures that are not doing this. 语法解析

16:59

That is already happening to a small extent. So I do want to highlight something that happened last year in Montana, where the state legislature passed a law that very meaningfully extends the concept of right to try. 语法解析

17:17

So I'm sure you know that at a federal level, there's this law that's saying if you're terminally ill and you've been through everything that's been approved, you can access things that have not been approved. You don't get reimbursed for it. You don't get insurance, but it's legal as long as someone has to prescribe it, of course. 语法解析

17:33

What they've done in Montana last year is they've said that if a treatment has got through phase one, so the safety part, and of course, you know, hundreds of 98% of treatments that get through phase one never get to phase three, right? And the ones that do don't get there for a very long time. 语法解析

17:53

This is FDA phase one, just for our audience so they know. Yeah. If something's got through phase one, then you can access it in Montana now, even if you're not terminally ill or ill at all. Again, you don't get insurance, it doesn't have to be prescribed, but it's a vast change. It means that… 语法解析

18:14

you know, we've got access to very many, I mean, huge numbers of treatments that otherwise would not be available. 语法解析

18:23

And, of course, the goal is to spread FOMO across the US and get other states to adopt the same legislation. The state senator, Ken Bogner, who spearheaded this in Montana, is now running for Congress, and obviously that will be a big part of his platform. We were somewhat involved in this. We seed-funded an organisation called A4LI, the American… 语法解析

18:49

the Alliance for Longevity Initiatives, which drafted the legislation and worked closely with Ken to make all of this happen. So I've been following this very closely. But yeah, coming back to the ProHUB cities, I honestly don't believe that that kind of initiative will move nearly fast enough without the incentive from elsewhere in the world to, you know, to compete. 语法解析

19:14

Yeah, wow, so many things happening. That's wonderful about Montana, getting access to these early-stage drugs that have been proven to be safe, but they haven't made it all the way through the system. Now, I guess all we need to do is get the definition of terminal illness modified to include 语法解析

19:35

aging and longevity, which is the terminal illness we all have. Let's talk about that for a moment because terminology is always an enormous barrier to progress. Yeah, language matters. So that may actually be the way to go. The problem that I've encountered throughout the time that I've been engaged in public outreach in this space, and so more than 20 years now, 语法解析

20:02

is fundamentally that the public are deeply suspicious of preventative medicine in general. They are suspicious of new medicines with some degree of justifications. New medicines sometimes don't work. 语法解析

20:18

But in particular, for preventative medicine, you know, the person's not yet sick and they are therefore scared that some new medicine might make them sick and they don't see any real, you know, risk-benefit ratio attraction there. So educating the public that actually prevention is a rather good thing is, you know, really important and really, really, really difficult. 语法解析

20:43

And framing of that, perhaps as simply saying, you're already sick, you've already got aging, is something that may make a difference. 语法解析

20:54

I'm definitely not a natural marketer. You know, I feel, you know, the way I put things out there, you know, to the world, it resonates with some audiences, but not with others. So I'm not the person to trust in terms of my judgment on that. But I do certainly think that it's an option and it's a vital thing to achieve to get the public more comfortable with preventative medicine for the chronic conditions of late life. 语法解析

21:23

Of course, my work, this work on damage repair that I focused on for all these years, is kind of treatment or prevention, depending on how you look at it. It's kind of the sweet spot between the two because it's designed to be applied to people who are not yet going downhill functionally, but equally it does actually turn back the clock in terms of removing damage and putting the body back into a state that approximates how it was at a younger age. 语法解析

21:48

And perhaps that can also be leveraged, you know, rhetorically. But again, you know, it takes marketers to figure that out. Yeah. Well, maybe you could talk a little bit about your work that you're doing, some of these interesting projects. We talked a little bit, again, before off camera, but I'm sure the audience would love to hear about that. Yeah, sure. So, yeah, of course. So, yeah. 语法解析

22:11

So to flesh out what I said a moment ago a little bit, my work for the past 20 or more years has been focused on implementing a really dramatic paradigm shift that I introduced in the year 2000. 语法解析

22:27

which was the idea that if we want to actually treat ageing, then it may be easier to reverse it than to slow it down. This sounds very counterintuitive, and it sure as hell was very counterintuitive to my colleagues. It took me several years to persuade anybody that I was not talking complete nonsense. 语法解析

22:45

But it's now a very widely accepted concept. And essentially, it comes down to the fact that if you want to slow aging down, essentially what you're doing is you're thinking of the body as a machine, you're making it run more cleanly. And that's really hard. You have to really understand how it runs in order to do that without having unintended consequences. 语法解析

23:07

And we just don't understand the body anywhere near well enough to be able to do that significantly. So people have basically got nowhere with that. 语法解析

23:16

But reversing aging is more a case of preventative maintenance. It's a case of simply getting rid of the damage that the body does to itself throughout life in the course of its normal operation and restoring the structure and composition of the body at the molecular and cellular level to something like how it was at a younger age, like in young adulthood. 语法解析

23:39

And you can do that in principle without understanding anything about how the body created the damage in the first place. And yet you achieve the goal of ensuring that the damage does not become abundant enough to exceed what the body is set up to tolerate and thus to make us sick and to make us suffer the chronic conditions of late life. So as I say, this concept has now been broadly embraced by the field, but you've still got to implement it. And implementing it 语法解析

24:07

comes fundamentally into two stages. And the reason it does is because it's a divide and conquer approach. Obviously, the body damages itself in many, many, many different ways. First step to understand how to actually get one's head around that and one's arms around it is to classify those many different types of damage into a manageable number of categories. And that's what I did back in 2000. I defined seven categories. 语法解析

24:29

And then to align each of those categories with a generic approach to actually doing the damage repair. Okay, so that's what I did. And some of those damage categories are much easier to address than others. So in my previous organization, Sense Research Foundation, we focused on the most difficult ones, the ones that other people were neglecting simply because other people had different incentive structures. They needed publications every 10 minutes. They needed, you know, to satisfy shareholders or whatever. 语法解析

24:58

We, being entirely funded by philanthropy, were able to avoid those constraints. And that's why we were able to work on really difficult things. 语法解析

25:06

And that was very successful. We progressed a number of projects over the years to the point where we could spin them out of startup companies. We did that half a dozen times. So that's all great. But it's only stage one because once you have implemented the various methods to repair this or that type of damage, and once you've got them reasonably working, at least in mice, 语法解析

25:29

you've still got to put them all together because each one individually is not going to make much of a difference to how long someone stays healthy. So the putting them together part is something that's only really become a thing in the past few years because it's only in the past few years that there's been enough progress on the individual things, even in mice, to have something to put together. And so now my new organization, LEV Foundation, that's what we're doing. As soon as we kicked off the new foundation, 语法解析

25:58

we kicked off our first really big project, a thousand mice being given four different treatments in various subsets of those four, treatments that address different types of damage in aging and seeing how well they synergize. So that project began a year ago. 语法解析

26:19

A key point to recognize is that we don't start when the mice are young. We start when they're already in middle age. So typical mice, healthy, normal, non-mutant mice, they typically live about two and a half years. And so we start when they're already one and a half years old. So they've got one year to go. 语法解析

26:38

Historically, the best that people have ever been able to achieve by doing anything to my starting when they're already one and a half years old is about four months of extension of subsequent life. And of course, the extra months are healthy months, which is good. We want that. But four is not very many. So we want to treble that. We want to get an entire year of extension of healthy life. 语法解析

27:06

in terms of both the average lifespan and the maximum. 语法解析

27:10

And we don't know whether we're going to be able to achieve that with the current experiment, but we've got plenty of other interventions and combinations of interventions lined up to test in this same way. And the only thing that's holding us back is funding. These experiments are very expensive. They are, well, the first one cost more than $3.5 million, and that's what each of them is going to cost. 语法解析

27:37

but in terms of, you know, information gains per dollar, we believe I'm very confident. I'm very sure that this is the most, you know, um, um, value for money experiment that's being done in the entire field right now. So anyone who feels like helping or wants to know more about this, you know, look at our website. I'm sure you'll put it in the show notes, avf.org. Uh, there's a link at the top to the next study. Um, and of course I'm always available. Um, 语法解析

28:04

by email and by Zoom or whatever to discuss anything like this with anyone who wants to help. - Yeah, that's so exciting. I mean, it's sort of like the interventions testing program 语法解析

28:18

With mice, except you've expanded it to more freedom of things you can test. And you're starting at the older age, which is a much more realistic model for what a human interaction would be, intervention would be. The intervention testing program has been going on for about 15 years now. And I don't want to disparage it. It's definitely done a lot. 语法解析

28:41

But yes, first of all, most of the interventions that they test, they start early in life. In fact, the reason that rapamycin is such a big deal these days, it all started with the interventions testing program accidentally starting their study rather late in life because they had real difficulty formulating the chow. 语法解析

29:04

So that's one problem, that most of their interventions start early. Second one is that, by and large, they're testing interventions individually. Again, they do sometimes combine things, but not often. But the biggest thing, the biggest limitation for the ITP is that they only do orally available things. They only put stuff in the chat. 语法解析

29:25

So that completely excludes cell therapies and gene therapies, which we are completely sure are going to be absolutely unavoidable if we want to get big results. So we are taking that on. We are biting that bullet. And that's a large part of why the experiments are expensive, but it's also absolutely essential. 语法解析

29:47

Yeah. Yeah. Um, or back to, back to language, just a couple of things. I want to be respectful of your time here, but just a couple of last things talking about language, uh, Misha Blaglosconi and Leonard Hayflick have this idea of, uh, 语法解析

30:02

you know they they they propose an idea that aging is due to uh damage cell damage and wear down but longevity is due to hyperfunction in other words with you know mtor and those sort of things is that all semantics or or what what's your take on that well so 语法解析

30:23

Calling one of these things aging and the other one longevity is unhelpful, I think. It kind of already obfuscates things because these words have already got so much baggage from other causes. 语法解析

30:34

But Michel Blagoscoloni's concept of hyperfunction is absolutely fine. It's completely valid, and it's not actually new either. It's really just the kind of modern expression, articulation, of something that was first put forward in the 1950s called antagonistic pleiotropy. Essentially, it just says that… 语法解析

30:58

In the same way that we don't have genes that would be useful late in life because evolution doesn't care about old individuals because they've already passed on their genetic information. Similarly, we don't develop genes that turn off other genes late in life unless that's also useful early in life. 语法解析

31:22

And so some genes will continue to do things that used to be good early in life and become bad. And various examples of this have been, concrete examples have been researched, especially in nematode worms. There's things that go on that are very overt in that regard. But it's a reasonable concept as applied to any species. 语法解析

31:51

The only real question is, how much of a contribution does that kind of thing make to ageing? At this point, we cannot reasonably argue that it contributes all that much. 语法解析

32:06

But of course, again, it depends on your definition. So some people would say, for example, that cancer is an example, that all of cancer is a result of antagonistic pleiotropy because essentially there's a trade-off between how well you 语法解析

32:25

regenerate tissues and how close to the wire you are in terms of letting cells go AWOL, so to speak. Like, let's just look at telomerase. You know, telomerase is a gene that if you absolutely blitz it and you do not have any expression and you can't turn it on, then, you know, it's very difficult for cancers in large animals like humans to grow large enough to kill you. 语法解析

32:51

But the fact is, unfortunately, we need a trace of telomerase in our regularly renewing tissues, like the blood or the gut lining, for example. And so it's not quite turned off. And that means that it can be epigenetically reactivated to an extent that will support cancer. And that's why 90% of human cancers have telomerase turned on at high levels. 语法解析

33:12

Things like that. So there's trade-offs all over evolution, and some of these trade-offs evolution has taken the trouble to optimize, and some of them it hasn't. So the concept of hyperfunction is fine, but oversimplifying the language with which it is described is a bad idea. 语法解析

33:31

The, you, you've talked about so many exciting things that are coming down the, down the road in longevity and the future. Maybe we'll just end up right now. We, you know, 语法解析

33:43

what do we do today, like right now with what's available? Is it lifestyle? Is it going to be supplements? Is it rapamycin and A-carbos? Is it plasmapheresis? What should we be doing now for our longevity today? Yeah, well, I have to be honest and say that my answer to that question has not changed over the years, and it still is. Write me a large check. 语法解析

34:08

At the end of the day, what matters is how much we can hasten the arrival of things that don't yet exist. 语法解析

34:16

things that do already exist, you know, there really isn't much. One thing that we always have to remember is that nearly everything that works well in laboratory organisms is certain not to work well in humans simply because it relies on emulating the metabolic response to calorie restriction. The 语法解析

34:42

You know, one thing that evolution has optimized is the metabolic response to famine. 语法解析

34:49

And, you know, it works pretty well to adjust metabolic priorities away from reproduction and in favor of maintenance so as to improve one's chances of outlasting the famine so that one can have offspring that won't just immediately die before having their own offspring on account of starving. Right. 语法解析

35:12

And that will make perfectly good evolutionary sense, but unfortunately, if you look at that logic even a little bit, you can see that long-lived species are not going to benefit very much, because long famines don't happen very often. And something has to happen reasonably often in order for evolution to care about it. So that means, yeah, that completely explains the very clear observation that's been around for 20 years at least, that 语法解析

35:37

there is this inverse correlation between how long a species lifespan is and how much benefit it gets from calorie restriction. You can multiply the lifespan of a nematode worm by five by doing the right kind of little tricks to it. Of course, I'm not talking about calorie restriction itself on its own. I'm talking also about genetic and pharmacological tricks to trick the organism into thinking it's on calorie restriction. 语法解析

36:03

And that's what nearly everything we have today, rapamycin, metformin, resveratrol, you know, that's what these things do in different ways. But still, that's what they do. So, yeah, I don't really expect to see anything significant in terms of extension of healthy lifespan in humans until we are ready for prime time with proper damage repair in the form of cell therapies and gene therapies of the sort that we're working on. 语法解析

36:30

What's the horizon timeframe for that, do you think? How long do we have to wait? Well, people have been asking me that question for a while. And yeah, I mean, I do not shy away from giving timeframe predictions, but I always make sure to emphasize that they are probabilistic. So I say we have a 50-50 chance of getting to what I've called longevity escape velocity within 12 to 15 years from now, so the late 2030s. 语法解析

36:56

And that's a point where we can take people who are, let's say, 60, biologically 60, average 60-year-olds, and rejuvenate them, not completely, but well enough that they won't be biologically 60 again for another 20 years or so. 语法解析

37:10

during which time people like myself will have improved the therapies so that we can rejuvenate the same people so they won't be biologically sick for a third time until they're 100 or 120 or whatever. This is what we call longevity escape velocity and you have to get those first 20 years in order to activate this kind of positive feedback loop, this kind of thing. 语法解析

37:33

You know, the term escape velocity is actually quite a good analogy with gravitational escape velocity. So, yeah, 12 to 15 years. But there's at least a 10% chance that we won't get there for 100 years because of any, you know, unanticipated obstacles that we may encounter. So I always emphasize the probabilities. 语法解析

37:53

Well, that's such an exciting idea. And thanks so much, Aubrey, for taking the time and spending with us today. You mentioned your website. Maybe you could mention it again and how people can follow you on social media. 语法解析

38:05

Absolutely. Please go to levf.org. L for longevity, E for escape, V for velocity, F for foundation. Everything is linked from there, including the conference. We run an annual conference. Of course, conferences have been a very big part of my work over the years in community building, and they still are. So our conference series now happens in Dublin in Ireland, and the next one is in mid-June, June the 13th to 16th. 语法解析

38:29

They are fantastic events scientifically and socially. And so I encourage everyone to go. The link to the conference website is right at the top of the LEV Foundation website homepage. And also there is a link to our next study that we want to do that I was talking about earlier to be a sequel to the study we're currently doing with a thousand mice. We want to do another one. 语法解析

38:53

And of course everything else about activities is there. You can email me at aubrey@ledf.org. You can find me on social media, on Twitter @AubreyDeGray, you know, everywhere you would expect. Great. Well, thanks so much for spending time with us today, Aubrey. And thanks also for the great work that you do. Well, thank you for having me and I look forward to next time. 语法解析

39:18

If you're enjoying this program, please hit that subscribe button or even better, leave a review. Your support makes it possible for us to create the quality programming that we're continually striving for. Can I start? Is it recording? It's already recording. Oh, sorry. 语法解析

39:36

This is for general information and educational purposes only, and it's not intended to constitute or substitute for medical advice or counseling, the practice of medicine or the provision of health care, diagnosis or treatment, or the creation of a physician, patient or clinical relationship. The use of this information is at their own use as risk. 语法解析

40:02

If you find this to be on the value, please hit that like button to subscribe to support the work that we do on this channel. And we take your suggestions and advice very seriously. So please let us know what you'd like to see on this channel. Thanks for watching and we hope to see you next time. You should say that. No, that's good. That's for you to say it. I think that's very good. Do you like it? You want to do it one more time or is that good? I think that was good. Yes! You need to save the recording. 语法解析

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Edit:2025.04.21<markdown>

Aubrey de Grey博士将在这个拓展思维的对话中揭示为什么逆转衰老可能比延缓衰老更容易，这挑战了关于人类寿命的传统认知。这位著名的生物老年学家概述了他获得主流科学界认可的损伤修复方法，尽管最初曾受到质疑。

在LEV基金会，DeGray博士正在进行一项包含一千只老鼠的研究，对中年老鼠结合四种不同的损伤修复干预措施。他的目标是实现整整一年的寿命延长，这在老鼠身上相当于人类的30年，远超通常能达到的四个月。

与依赖饮食调整的传统方法不同，这个雄心勃勃的项目结合了先进的细胞和基因疗法，同时针对多种与年龄相关的损伤。现在，展望未来，DeGray博士给出了他特有的概率预测：在12到15年内有50%的机会达到“长寿逃逸速度”。

这将使60岁的人能够返老还童，使他们再次保持60岁的生物年龄20年，在此期间进一步的进步将实现额外的返老还童周期，可能为今天许多活着的人创造无限的健康寿命。

我们正在经历一场长寿知识的革命，发展速度比以往任何时候都快。在过去五年中，你认为最令人惊讶的事情是什么？

我想整个行业最大的惊喜是HEvolution的出现，沙特王室承诺在20年内每年投入10亿美元用于长寿研究和开发。这比我们预期的要花更长时间才能见效。他们当然还没有达到每年投入10亿美元的水平，但他们已经打下了正确的基础。他们确实找到了非常合适的人选Mehmood Khan来负责。

他们也有非常优秀的高层管理人员。我认识这些人，我真的很信任他们能把事情做好。所以这绝对是件大事，尽管还没有完全见效，但绝对是个巨大的进步。

关于HEvolution的快速问题，HEvolution似乎与这个领域的其他大公司或大项目类似，比如最初由谷歌支持的Calico，然后是由包括Jeff Bezos在内的多位资助者支持的Altos，现在是HEvolution。这三家公司有何不同？它们的做法有何不同？

正如你所说，这些公司在资金规模上即使不如HEvolution，也在相近范围内。它们对我来说不那么意外，因为我早就知道谷歌双胞胎和Bezos对这个领域有浓厚兴趣。事实上，令我非常沮丧的是，他们之前完全没有提供慈善帮助，但他们就是那种不太相信非营利组织能在技术领域做好事的人。

最终他们决定做一些名义上是为了盈利的事情，尽管他们实际上并不需要从这些事情中赚钱。说实话，Calico完全是个灾难。它的组建方式非常糟糕，没有真正的产品线。它没有真正的方法将已验证的概念转化为产品。

它在好奇心驱动的基础科学方面确实有高质量的人员，也有实际的业务端，由曾经负责Genentech的人运营的Genentech Mark II，但中间没有任何连接两者的部分。所以如果它真的做出什么有用的事情，那完全是运气。这绝对是个悲剧。

我对Altos的期望要高得多。Bezos早在2006年就开始和我讨论衰老问题。同样，从未给我们任何资金，但最终决定在这个领域投入适当的资金。Altos的好消息是他们聘请了该领域的许多顶尖人才，这意味着没有任何一种思想流派会主导那里的工作。整个运作方式有点奇怪。Bezos从不谈论它。它甚至只算是半公开宣布他是主要资助者。他们不允许将自己描述为长寿公司。但我确实相信他们会做出好的工作。

当然还有其他公司。加密货币领域的许多重要人物也开始涉足这个领域。其中一些人在慈善方面很有帮助。Vitalik Buterin是多年来给我和我的各种组织提供大量资金的知名人士之一。创建Coinbase的Brian Armstrong也创建了一家公司New Limit，资金非常充足。

当然还有Retro，这可能是这些公司中最有前途的，因为Sam Altman决定投入适当的资金，大约两亿美元，而且他做对了。他实际上找到了一位真正的长寿倡导者Joe Betz-Lacroix来运营这个项目，他是我的好朋友，我对Retro能取得巨大成就抱有很高的期望。

与其他公司相比，对Retro的乐观是基于这个人的领导能力，还是他们采用了不同的策略或某种特定的长寿方法？主要是领导能力。Joe是那种真正理解目标、像工程师一样思考的人。所以他会把事情做好。

在这个话题上，在我们回到长寿问题之前，你提到了Vitalik Buterin，我们刚才在镜头外谈到了你在洪都拉斯Prospera的经历，那里刚刚举办了一个精彩的会议。也许你可以向我们的观众介绍一下这个情况，以及你为什么对此感到兴奋。

这一切始于几个月前在蒙特内格罗举办的一个名为Zuzalu的非凡活动。这基本上是由Vitalik Vissarion构想和资助的。他能够召集几百人参加为期两个月的活动。我只参加了一周。当然，很多人参加了大部分活动。

这个活动的理念是探索比传统会议更长、但仍然有几百人参加的形式是否能做到传统形式做不到的事情。基本上，它是否能更有效地进行社区建设、思想交流、相互教育等。它非常成功。所以整个理念已经成为在全球各地以各种方式举办此类活动的计划。

第二个活动名为Vitalia，正在举行。实际上，它从1月6日开始。原本计划持续到3月1日。他们实际上又延长了一个月。我参加了第一个月。它真的会带来改变。Vitalia与Zuzalu的主要区别在于Vitalia是在Prospera举行的。

Prospera是洪都拉斯的一个特别经济区，实际上不在大陆上。它在一个叫Roatan的岛上。它被设置为拥有特别经济区可能想要的一切。它非常安全。在大多数方面它实际上像西方。特别是，他们想做的是强调生物医学创新。因此他们在法律上设置了自己，以最大限度地激励诊所和公司在那里注册或搬迁，并完成他们在更传统的司法管辖区无法做到的事情。

特别是监管结构，因为他们有非常广泛的法律自治权，不包括刑法或军事等，但他们基本上拥有其他一切，他们可以建立自己的监管结构。他们非常清楚地表明，在测试新医疗干预措施时人们需要的安全性可以在不妥协的情况下，在比美国等地短得多的时间内实现。因此，这对很多人来说相当有吸引力。

我对这些人评价再高也不为过。他们非常非常能干。他们有巨大的能量。可以说有很多来自年轻一代的代表。他们把事情做对了。所以我要说，我认为很可能在短短几年内，Prospera将成为全球医疗旅游的中心。这不仅仅是因为像Vitalia这样的事件，但这当然给了它最初的推动力。

这种事情发生得越多越好。因此，今年晚些时候和明年，全球其他地方还计划举办其他类似活动。实际上，Vitalik本人有点退居二线。据我所知，他没有为Vitalia提供资金，也没有出席，而他确实为Zuzalu做了这些。

不过，许多其他知名人士确实出席了，所以我不是唯一一个。非常强调网络国家的概念，即去中心化、法律自治的实体。这个领域的权威Balaji Srinivasan也亲自到场。其他一些人也参与其中，这些人会提升整个企业的信誉和声誉。因此我相信它具备了产生巨大影响所需的一切。

因此Vitalia将成为那里一个持续的组织。它会继续下去。它不仅仅是一次性会议，而是长期的。所以Prospera是特别经济区的名称。Vitalia，我认为是一个灵活的概念。它原本应该是这个为期两个月、到3月1日结束的活动。他们已经延长了它。那些从Vitalia诞生或被Vitalia吸引到Prospera的公司、实体，在许多情况下显然也将是永久性的。所以Vitalia是否永久有点灰色地带。

你提到了其他几个会议，世界各地即将举行的会议，你对此感到兴奋。能分享一些吗？

我们不要称它们为会议。因为把持续两个月的事情称为会议有点困难。他们实际上称之为快闪城市。但是的，世界各地还有其他计划。我知道非洲有一个正在计划，我想是在桑给巴尔。南美洲有几个想法。乌拉圭显然在特别经济区方面有特别友好的立法。所以那里有很多想法。我不是这方面的专家。你应该和参与其中的人谈谈。

那些负责这个项目的人才能理解。但这真是个令人兴奋的领域。所以听起来你认为生物技术项目的发展在这种情况下，没有官僚机构的过度审查或FDA的拖累，许多人认为在很多情况下这是不必要的。我想强调的是，这是近期内最重要的事情，在几年内，因为如果这成功了，它将产生巨大的FOMO（害怕错过）。传统司法管辖区，无论是美国还是其他地方，将有巨大的动力去现代化他们的监管结构，以与那些没有这样做的结构竞争。

这已经在很小程度上发生了。所以我想强调去年在蒙大拿州发生的事情，州立法机构通过了一项法律，非常有意义地扩展了“尝试权”的概念。我相信你知道，在联邦层面有这项法律说，如果你病入膏肓，已经尝试了所有获批的治疗方法，你可以使用未获批的治疗方法。你不会得到报销。你没有保险，但只要有人开处方，它就是合法的。

去年他们在蒙大拿州做的是说，如果一个治疗方法通过了一期试验，也就是安全性部分，当然，你知道，98%通过一期的治疗方法从未进入三期，对吧？而那些进入三期的也需要很长时间。这是FDA的一期，为我们的观众说明一下。是的。如果某件事通过了一期，那么你现在就可以在蒙大拿州使用它，即使你不是病入膏肓或根本没有生病。同样，你没有保险，不必开处方，但这是一个巨大的变化。这意味着我们可以获得非常多，大量的治疗方法，否则将无法获得。

当然，目标是让FOMO在美国蔓延，让其他州采用相同的立法。州参议员Ken Bogner在蒙大拿州领导了这项工作，现在正在竞选国会议员，显然这将是他平台的重要组成部分。我们某种程度上参与了这件事。我们为名为A4LI的组织提供了种子资金，美国长寿倡议联盟，他们起草了立法，并与Ken密切合作使这一切成为现实。所以我一直密切关注这件事。

但是，回到ProHUB城市，我真的不相信这种倡议会足够快地推进，除非来自世界其他地方竞争的激励。蒙大拿州的事情很棒，能够获得这些早期阶段的药物，它们已被证明是安全的，但还没有完全通过系统。现在，我想我们需要做的就是修改绝症的定义，包括衰老和长寿，这是我们所有人都有的绝症。让我们谈谈这个，因为术语一直是进步的巨大障碍。

是的，语言很重要。所以这实际上可能是前进的方向。我在这个领域从事公众宣传工作时遇到的问题，已经有20多年了，基本上是公众对预防性医学普遍深表怀疑。他们对新药有一定程度的合理怀疑。新药有时不起作用。特别是对于预防性医学，人们还没有生病，因此他们担心某些新药可能会让他们生病，他们看不到任何真正的风险收益比吸引力。因此教育公众预防实际上是一件相当好的事情非常重要，也非常非常非常困难。

也许可以简单地表述为你已经生病了，你已经衰老了，这可能会产生影响。我绝对不是天生的营销人员。我觉得我表达的方式对某些观众有共鸣，但对其他人没有。所以我不是判断这方面的人选。但我确实认为这是一个选择，而且让公众对晚年慢性病的预防性医学更放心是至关重要的。

当然，我的工作，这些年来我一直专注于损伤修复，可以说是治疗或预防，取决于你怎么看。它介于两者之间的最佳点，因为它旨在应用于那些功能尚未下降的人，但同样它确实通过消除损伤并将身体恢复到更年轻时的分子和细胞水平的结构和组成来逆转时钟。也许这也可以在修辞上加以利用。但这需要营销人员来弄清楚。

也许你可以谈谈你正在做的工作，其中一些有趣的项目。我们之前也在镜头外谈过，但我相信观众会想听听。所以稍微详细说明我刚才所说的，我过去20年或更长时间的工作一直专注于实施我在2000年引入的一个非常戏剧性的范式转变。

这个想法是，如果我们想真正治疗衰老，那么逆转它可能比减缓它更容易。这听起来非常违反直觉，对我的同事来说当然也非常违反直觉。我花了好几年时间才说服任何人我没有在胡说八道。但现在这是一个被广泛接受的概念。基本上，它归结为如果你想减缓衰老，基本上你把身体看作一台机器，你让它运行得更干净。这真的很难。你必须真正理解它是如何运行的才能做到这一点而不产生意想不到的后果。

我们对身体的了解远远不足以显著做到这一点。所以人们基本上在这方面毫无进展。但逆转衰老更像是预防性维护。它只是简单地消除身体在其正常运作过程中对自己造成的损伤，并将身体在分子和细胞水平上的结构和组成恢复到更年轻时的状态，比如青年时期。

你可以在原则上做到这一点，而不需要理解身体最初是如何产生损伤的。然而你实现了确保损伤不会变得足够多以至于超过身体设定的耐受限度，从而使我们生病并遭受晚年慢性病的目标。正如我所说，这个概念现在已被该领域广泛接受，但你仍然需要实施它。

实施它基本上分为两个阶段。原因是这是一种分而治之的方法。显然，身体以许多许多不同的方式损伤自己。第一步是理解如何真正掌握这一点，并将这些许多不同类型的损伤分类为可管理的几类。这就是我在2000年所做的。我定义了七类。然后将每一类与实际的损伤修复通用方法对应起来。好的，这就是我所做的。

其中一些损伤类别比其他类别更容易解决。所以在我之前的组织Sense Research Foundation，我们专注于最困难的类别，那些其他人忽视的类别，仅仅因为其他人有不同的激励结构。他们需要每十分钟发表一篇论文。他们需要满足股东或其他什么。我们完全由慈善资助，能够避免这些限制。这就是为什么我们能够研究真正困难的事情。

这非常成功。多年来我们推进了许多项目，直到我们可以将它们分拆成初创公司。我们这样做了六次。所以这都很棒。但这只是第一阶段，因为一旦你实施了修复这种或那种损伤的各种方法，并且至少在小鼠身上取得了一定效果，你仍然需要将它们全部结合起来，因为每一种方法单独对保持健康的时间影响不大。所以将它们结合起来是最近几年才真正开始的事情，因为只有最近几年在个体方法上才有足够的进展，即使在小鼠身上，才有东西可以结合。

所以现在我的新组织LEV Foundation就在做这件事。我们一启动新基金会，就启动了第一个真正的大项目，一千只小鼠接受四种不同的治疗，这些治疗的子集针对衰老的不同类型损伤，看看它们协同作用的效果如何。这个项目一年前就开始了。

关键是要认识到我们不是在小鼠年轻时开始。我们在它们已经中年时开始。所以典型的小鼠，健康、正常、非突变的小鼠，通常寿命大约两年半。所以我们在它们一岁半时开始。所以它们还有一年寿命。历史上，人们通过任何方法对一岁半的小鼠实现的最好效果是延长后续寿命约四个月。当然，额外的几个月是健康的月份，这很好。我们想要这样。但四个月不是很多。所以我们想将其增加两倍。我们想将健康寿命延长整整一年。

就平均寿命和最大寿命而言。我们不知道我们是否能用当前的实验实现这一点，但我们还有很多其他干预措施和干预措施组合准备以同样的方式测试。唯一阻碍我们的是资金。这些实验非常昂贵。第一个实验花费了超过350万美元，每个实验都会花费这么多。但就每美元获得的信息而言，我们相信我非常自信。我非常确定这是整个领域目前性价比最高的实验。所以任何想提供帮助或想了解更多的人，看看我们的网站。我相信你会把它放在节目说明中，avf.org。顶部有一个链接指向下一个研究。当然我随时可以通过电子邮件和Zoom或其他方式与任何想提供帮助的人讨论这类事情。

这有点像干预测试计划用老鼠，但你扩大了可以测试的东西的自由度。而且你从老年开始，这更接近人类干预的现实模型。干预测试计划已经进行了大约15年。我不想贬低它。它确实做了很多。但首先，他们测试的大多数干预措施都是从生命早期开始的。事实上，雷帕霉素如今如此重要，这一切都始于干预测试计划意外地在生命后期开始他们的研究，因为他们在配制饲料时遇到了真正的困难。

所以这是一个问题，他们的大多数干预措施开始得早。第二个问题是，基本上他们测试的是单独的干预措施。他们有时会结合一些东西，但不经常。但最大的问题，干预测试计划最大的限制是他们只做口服的东西。他们只把东西放在饲料里。所以这完全排除了细胞疗法和基因疗法，我们完全确定如果想要取得大成果这些是绝对不可避免的。所以我们正在做这件事。我们正在啃这块硬骨头。这是实验昂贵的一个重要原因，但这也绝对必要。

回到语言，还有几件事。我想尊重你的时间，但最后几件事关于语言，Misha Blaglosconi和Leonard Hayflick有这个想法，他们提出衰老是由于损伤细胞损伤和磨损，但长寿是由于功能亢进，换句话说，像mTOR这类东西。这都是语义还是你有什么看法？

将其中一种称为衰老，另一种称为长寿没有帮助，我认为。这已经让事情变得模糊，因为这些词已经从其他原因中获得了太多包袱。但Michel Blagoscoloni的功能亢进概念完全没问题。它完全有效，实际上也不是新的。它只是对抗性多效性（antagonistic pleiotropy）的现代表达方式，这个概念最早在1950年代提出。基本上，它只是说就像我们没有对生命后期有用的基因，因为进化不关心老年个体，因为他们已经传递了他们的遗传信息。同样，我们不会发展那些在生命后期关闭其他基因的基因，除非这在生命早期也有用。

所以一些基因会继续做那些在生命早期有益而在后期有害的事情。这方面的具体例子已经被研究，特别是在线虫中。有一些非常明显的事情。但这是一个适用于任何物种的合理概念。唯一真正的问题是，这种事情对衰老的贡献有多大？在这一点上，我们不能合理地认为它贡献很大。但当然，这取决于你的定义。所以有些人会说，例如，癌症就是一个例子，所有癌症都是对抗性多效性的结果，因为基本上有一个权衡，关于你如何再生组织和你让细胞失控的程度有多接近。

比如，看看端粒酶。端粒酶是一种基因，如果你完全破坏它，没有任何表达，也无法开启，那么像人类这样的大型动物中的癌症很难生长到足以杀死你的程度。但事实是，不幸的是，我们需要一点端粒酶在我们的定期更新组织中，比如血液或肠道内壁。所以它并没有完全关闭。这意味着它可以表观遗传地重新激活到一定程度，从而支持癌症。这就是为什么90%的人类癌症中端粒酶高度活跃。

诸如此类的事情。所以进化中到处都是权衡，其中一些进化已经费心优化，而另一些则没有。所以功能亢进的概念没问题，但用来描述它的语言过于简化是个坏主意。

你谈到了这么多令人兴奋的事情，关于长寿和未来的发展。我们今天能做什么，现在就用现有的东西？是生活方式吗？是补充剂吗？是雷帕霉素和阿卡波糖吗？是血浆置换吗？我们今天应该为长寿做些什么？我必须诚实地说，我对这个问题的答案多年来没有改变，现在仍然如此。给我开一张大支票。归根结底，重要的是我们能多快实现那些还不存在的东西。

已经存在的东西真的不多。我们必须记住的一件事是，几乎所有在实验室生物中效果良好的东西在人类中肯定不会效果很好，仅仅因为它依赖于模拟热量限制的代谢反应。进化已经优化的一件事是对饥荒的代谢反应。它相当好地调整了代谢优先级，从繁殖转向维护，以提高度过饥荒的机会，这样一个人可以有后代，而不会因为饥饿而立即死亡。

这从进化角度完全合理，但不幸的是，如果你稍微看看这个逻辑，你会发现长寿物种不会受益太多，因为长期饥荒不常发生。而有些事情必须经常发生，进化才会关心它。所以这意味着，这完全解释了至少20年来一直存在的非常明显的观察结果，物种寿命与其从热量限制中获得的益处之间存在这种反比关系。

你可以通过对线虫做正确的小技巧将其寿命延长五倍。当然，我说的不是单独的热量限制本身。我说的是基因和药理技巧，诱骗生物体认为它在进行热量限制。这就是我们今天几乎所有东西的作用方式，雷帕霉素、二甲双胍、白藜芦醇，这些东西以不同的方式起作用。但仍然，这就是它们的作用。所以，我真的不期望看到人类健康寿命的任何显著延长，直到我们准备好用适当的损伤修复方法，比如我们正在研究的细胞和基因疗法。

你认为这需要多长时间？我们需要等多久？人们问我这个问题已经有一段时间了。我不回避给出时间预测，但我总是强调它们是概率性的。所以我说我们有50%的机会在未来12到15年内（即2030年代末）达到我所说的长寿逃逸速度。这是一个临界点，我们可以让60岁的人，生物年龄60岁的人，不是完全地，但足够好地返老还童，使他们20年内不会再次达到生物年龄60岁。

在此期间，像我这样的人将改进治疗方法，这样我们可以再次返老还童这些人，使他们直到100岁或120岁或更久才会第三次达到生物年龄60岁。这就是我们所说的长寿逃逸速度，你必须先获得这20年才能激活这种正反馈循环。逃逸速度这个术语实际上与重力逃逸速度的类比相当好。所以，12到15年。但至少有10%的可能性我们需要100年才能实现，因为任何我们可能遇到的未预料到的障碍。所以我总是强调概率。

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Edit:2025.04.21

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