科学与数学ldeming.com
长寿研究入门指南
Beginner's guide to longevity research
2018 — 2022，它一次次回到首页
黑点是上首页（≥ 50 分）的那次投稿，空心点是没冲上去的投稿，点越大分数越高。
导读
这是 Laura Deming 撰写的一份长寿研究入门 FAQ，用相对通俗的方式梳理衰老与延寿研究的主要议题，并附有大量参考文献。作者有衰老研究背景，并创办了专注长寿领域的 Longevity Fund，因此这份材料适合作为了解该领域现状与争议的起点。
为什么经久不衰：它简明、带出处地梳理了一个容易被炒作的研究领域，而评论区对证据强度和商业化前景的质疑，让今天读来仍有参考价值。
HN 评论精选
热量限制研究的对照组是过度喂食动物，且动物到人类的外推性差，长寿研究的证据被高估。
我提供一个逆向观点：就目前的范围而言，长寿研究的准确性和实用性大概和 Ray Kurzweil 90 年代的预测差不多。以热量限制为例，现在非常流行。问题是，我们掌握的所有证据都来自小鼠或更低等动物，而且比较的是热量限制的动物与被强行喂到肥胖的动物。我重复一遍：在显示热量限制延长动物模型寿命的研究中，它们并不是与正常饮食的动物比较。所以完全可能所有热量限制研究结果只是在证实肥胖缩短寿命这一事实。这还没提到动物模型与人类之间的对应关系极差。尽管这是我们最好的工具，但药物在动物身上证明成功后还需要经过三个阶段的人体测试，这是有充分理由的。就热量限制而言，我们甚至在猴子身上都没有一致的正向结果，只有在啮齿动物身上有。这些长寿的东西有没有在人类身上测试过？显然没有，因为需要几十年。
semi-extrinsic查看英文原文
I'll offer a contrarian view: longevity research, as in the current scope, is about as accurate and useful as Ray Kurzweil's predictions from the 90s. Let's take caloric restriction, for instance, which is all the rage. Trouble is, all of the evidence we have is in mice or lesser animals, and the comparison is animals on caloric restriction against animals being force fed to the point of obesity. Let me repeat that: in research that shows caloric restriction increasing lifespan in animal models, they are not comparing to animals on a normal diet. So it's entirely plausible all this caloric restriction research findings is just confirmation of the fact that obesity shortens lifespans. This isn't even touching on the point that correspondence between animal models and humans is abysmally bad. It's the best we have, but there's a very good reason drugs need to go through three stages of human testing after it's been proven successful in animals. With caloric restriction, we don't even have consistent positive results in monkeys, only in rodents. Has any of this longevity stuff ever been tested in humans? Obviously not, since it would take many decades. Some pointers for further reading: https://www.sciencedirect.com/science/article/pii/S0891584914002317 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765579/
介绍作者 Laura Deming 与 Longevity Fund，认为修复衰老根因的研究被低估，是投资机会。
这篇综述的作者 Laura Deming 运营 Longevity Fund，并有衰老研究背景。我认为她值得祝贺，因为她比其他人早几年建立了专注于长寿的基金，现在 Jim Mellon 的 Juvenescence、Methuselah Fund、Apollo Ventures 等也加入了。按照 SENS Research Foundation 修复已知衰老根因模式的再生研究是一个巨大的套利机会。大多数人仍然不理解，因此严重低估了这个领域的研究和公司。在衰老细胞清除方面这种情况正在改变，但另外六七个新兴研发领域正处在衰老细胞清除 2010 年的位置——无人关注、资金少、估值低，而在动物模型中展示再生技术后估值有巨大突破潜力。即使不算其他成功，仅凭投资 Unity Biotechnology，Longevity Fund 很可能也会表现不错。这篇文章是有用概述，附大量参考文献，很好地说明了衰老研究界目前的工作类型。
reasonattlm查看英文原文
The author of this overview, Laura Deming, runs the Longevity Fund, and has a research background in the study of aging. She merits congratulations for being, I think, the first by a few years to put together a longevity-focused fund, now joined by e.g. Jim Mellon's Juvenescence venture, Methuselah Fund, Apollo Ventures, etc. Rejuvenation research after the SENS Research Foundation model of repairing the known root causes of aging is a massive arbitrage opportunity. It remains the case that most people just don't get it, and are thus enormously undervaluing research and companies in this space. That is changing in senescent cell clearance, but six or seven other nascent areas of research and development are in exactly the same position senescent cell clearance was in back in 2010 - no attention, little funding, low valuation, huge potential for breakout gains in said valuation on producing a technology demonstration for rejuvenation in animal models. It seems likely that the Longevity Fund will do well on the basis of having invested in Unity Biotechnology alone, even putting aside any other successes. The article linked here is a useful overview, with copious references, of the type of work presently taking place in the aging research community. It well illustrates that, aside from senescent cell clearance, nearly everything that counts as a major interest by funding and number of scientists involved is a form of tinkering with stress response biochemistry to modestly slow aging - not addressing root cause molecular damage by repairing it, but rather messing with metabolism to slow damage accumulation. Nowhere near as helpful. Given what we know, where the data exists to compare outcomes between short-lived and long-lived species, the approach of altering metabolic processes to enhance beneficial stress response mechanisms is not going to move the needle all that far in humans. The results should be exercise-like and calorie-restriction-like in that they have worthwhile effects on long-term health, assuming that the cost of development and treatment is low, but they won't add much more to life expectancy than those two items are capable of achieving - which means perhaps the low end of five to ten years at best in our species, assuming life-long commitment to the intervention. Given that senescent cell clearance is a going concern, and other damage repair approaches such as cross-link breaking should follow in the years ahead, we can hope that the focus of the research community will shift as other approaches prove themselves much more cost-effective and successful.
文章简短且引用丰富；间歇性禁食和生酮是读者可进一步了解的实践方向。
这是一篇非常棒的写作，每个主题都简短明了，并附有大量来源。对于想找可操作建议的人，可以去间歇性禁食的 Reddit 板块。这是降低热量摄入并增加自噬的好方法。做间歇性禁食的人通常也采用文中提到的生酮饮食。
Jemmeh查看英文原文
This is a pretty fantastic writeup, short and simple on each topic with loads of sources. For those looking for something actionable, you may want to head to the reddit board for intermittent fasting. It's a good way to lower your caloric intake and increase autophagy. People doing intermittent fasting often also eat a keto diet that is mentioned in the writing as well. https://www.reddit.com/r/intermittentfasting/ https://www.reddit.com/r/keto/
长寿领域上市公司股价大幅下跌，商业化前景受挫。
所有获得投资支持的上市公司现在都跌得很惨。Metacrine -92%（一年），Unity Biotechnology -86%，Decibel Therapeutics -80%，Precision Biosciences -62%。
gw67查看英文原文
All the public companies backed are now down badly. - METACRINE -92% (1 year) - Unity biotechnology -86% (1 year) - DECIBEL THERAPEUTICS -80% (1 year) - PRECISION BIOSCIENCES -62% (1 year) https://www.longevity.vc/
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