Anti-Aging: State of the Art

[-]Matthew Barnett5y*520

As an effective altruist, I like to analyze how altruistic cause areas fare on three different axes: importance, tractability and neglectedness. The arguments you gave for the importance of aging are compelling to me (at least from a short-term, human-focused perspective). I'm less convinced that anti-aging efforts are worth it according to the other axes, and I'll explain some of my reasons here.

The evidence is promising that in the next 5-10 years, we will start seeing robust evidence that aging can be therapeutically slowed or reversed in humans.
[...]
In the lab, we have demonstrated that various anti-aging approaches can extend healthy lifespan in many model organisms including yeast, worms, fish, flies, mice and rats. Life extension of model organisms using anti-aging approaches ranges from 30% to 1000%:

When looking at the graph you present, a clear trend emerges: the more complex and larger the organism, the less progress we have made on slowing aging for that organism. Given that humans are much more complex and larger than the model organisms you presented, I'd caution against extrapolating lab results to them.

I once heard from a cancer researcher that we had, for all ... (read more)

[-]JackH5y*270

I am also an effective altruist and have been involved in the movement since 2012. I and others think that anti-aging and donating to SENS is probably a more important cause area than most EA cause areas (especially short-term ones) besides X-risk for the reasons below.

As a side note, from the longer (200+ comment) discussion about anti-aging from an EA perspective on the EA Facebook group here, the main objection that held weight seemed to be 'bang for buck', and is also addressed below.

In this piece: Why SENS Makes Sense and this piece: A general framework for evaluating aging research. Part 1: reasoning with Longevity Escape Velocity Emanuale Ascani evaluates the cost effectiveness of anti-aging, and donations to SENS Research Foundation using the EA criteria of scale, neglectedness and tractability. His estimation of cost-effectiveness of a SENS donation is $2.50 per 1000 quality-adjusted years life years saved, which dwarfs most other short-term cause areas in EA.

In terms of tractability and neglectedness, I'll add a few more thoughts:

(1) Tractability

I understand that considering the models of aging (mice, flies, yeast etc.) alone might give the impression that the... (read more)

[-]Matthew Barnett5y140

I appreciate the detailed and thoughtful reply. :)

I and others think that anti-aging and donating to SENS is probably a more important cause area than most EA cause areas (especially short-term ones) besides X-risk for the reasons below.

I agree that anti-aging is neglected in EA compared to other short-term, human focused cause areas. The reason is likely because the people who would be most receptive to anti-aging move to other fields. As Pablo Stafforini said,

Longevity research occupies an unstable position in the space of possible EA cause areas: it is very "hardcore" and "weird" on some dimensions, but not at all on others. The EAs in principle most receptive to the case for longevity research tend also to be those most willing to question the "common-sense" views that only humans, and present humans, matter morally. But, as you note, one needs to exclude animals and take a person-affecting view to derive the "obvious corollary that curing aging is our number one priority". As a consequence, such potential supporters of longevity research end up deprioritizing this cause area relative to less human-centric or more long-termist alternatives.

I wrote a post about how anti-aging mi... (read more)

[-]JackH5y130

I agree that anti-aging is neglected in EA compared to other short-term, human focused cause areas. The reason is likely because the people who would be most receptive to anti-aging move to other fields. As Pablo Stafforini said

I agree with Pablo's reasoning as to why anti-aging has not taken off in the EA community.

If humans make continuous progress, then eventually we'll get here. I have no issue with that prediction. But my objection concerned the pace and tractability of research. And it seems like there's going to be a ton of work going from modest treatments for aging to full cures.

I agree that the 'white mirror' scenario might be some time off (even 100+ or 1000+ years away), but remember that we only need to reach longevity escape velocity for everyone on Earth to make it to the 'white mirror' scenario, not reach the 'white mirror' scenario right away. For example, within the next 50 years, we might have drugs that keep us alive for another 100 years, meaning even if it takes 80 years to develop drugs that keep us alive for 1000 years, and then it takes 800 years for us to develop drugs that would bring us to the 'white mirror' scenario, we would still reach it.... (read more)

2DirectedEvolution3y

I'd also highlight that we have fine-grained empirical data about clinical trial success rates, though not for geroscience-based therapies. The overall success rate for a therapeutic can range from 3.4% (cancer drugs) to 33.4% (vaccines), with an average including oncology of 13.8% and an average excluding oncology of 20.9%. Some of the most promising drug candidates, like rapamycin, have already passed clinical trials for other indications, so we know they're safe. The work now is to show they can be safe enough at lower doses to justify giving them to healthy people.

6Victorel Petrovich5y

I have to disagree on 2 points: 1. "When looking at the graph you present, a clear trend emerges: the more complex and larger the organism, the less progress we have made on slowing aging for that organism" -- the trend is not clear. Rather, the worms are an outlier on that graph. Mice are much more complex than flies and killifish (and much closer to humans) and yet, the results achieved are on par. 2. "The fact that there are 130 companies working on the problem with only minor laboratory success in the last decade indicates that the marginal returns to new inputs is low. " -- Most of them have their individual approaches to "the problem" . There are orders of magnitude more variables that affect the health and lifespan, and those companies are trying just a few of them. So, they are just scratching the surface of what it needs to be tried and done. More researchers and companies is definitely what is needed.

1Matthew Barnett5y

You're right about (1). I seemed to have misread the chart, presumably because I was focused on worms. Concerning (2), I don't see how your argument implies that the marginal returns to new resources are high. Can you clarify?

7Victorel Petrovich5y

It depends on what you mean by "new resources". In your text, you wrote "One more researcher, or one more research grant will add little to the rate of progress. " -- and that's what I argued against, above. Simply put, more researchers & companies=> more longevity-influencing factors to be evaluated => higher chance to find ones that work, and work better.

4Chris Hibbert5y

This seems untrue on its face. What we mean by "curing aging" is negligible senescence. The best that has been achieved in mice is doubling their life spans, AFAICT. Extended (human) lifespan would be nice, but it's not the goal.

2Matthew Barnett5y

And presumably what the cancer researcher meant by curing cancer was something like, "Can reliably remove tumors without them growing back"? Do you have evidence that we have not done this in mice?

3JackH5y

I assumed that was a typo and that you meant curing cancer in mice. We have definitely have not yet 'cured aging' in mice, which is called robust mouse rejuvenation (RMR). RMR is usually discussed in the context of timelines for longevity escape velocity (LEV), as a relevant milestone on the way to LEV. Aubrey de Grey has put RMR timelines as occuring as soon as 2022, and LEV occurring by 2036.

2Matthew Barnett5y

Oops, that was a typo. I meant curing cancer. And I overlooked the typo twice! Oops.

[-]Eli Tyre5y260

This was great.

Some things that made it great:

It was just in the sweet spot of length. Taking notes, this took me a half hour to read. (I think the ideal is in the 30 minutes to 60 minute range, so doubling the post would have been fine, but more than that would have been overwhelming).
It was written clearly.
It was full of links that I can use to follow up on the places that I am most interested / confused about.

I would love to read more posts like this one, on a whole variety of topics, and would be glad to help subsidize their production if there was a way to organize that.

[-]JackH5y100

Thanks for the compliment!

Although it only took two days to write, it was the product of several months of thinking about the topic, and putting the pieces together.

That said, if you'd like to sponsor me to complete this sequence and/or create more content like this, I would be more than happy to. You can have a look at other content I've created for MindsetHealth.com.

Please feel free to drop me a line at jtt.harley@gmail.com

[-]DirectedEvolution5y170

I want to consider this post from a decision-making perspective. How can it inform my own future decisions?

First of all, this is the applied goal underlying my graduate-level research. As I continue to learn more about my field of tissue engineering, bioprinting, and regenerative medicine, I might be able to contribute to this growing anti-aging movement. So this post can inform my reading and writing decisions.

Without meaning to be rude, I'm not certain that these sources or this post is credible, simply because I'm only starting to read it and understand it myself. This question is due to my own lack of knowledge, not any issue with the OP. However, it might make a good starting point. It might be valuable to look at the sheer amount of reading it would entail, and the level of mastery I'd like to attain in this domain.

If I wanted to commit a total of 50 hours studying this body of literature, is this post the best place to start? If not, what is? I don't have any better ideas. Perhaps the key question is really where to start within this post.

I think I'm having these credibility and "where to start" concerns because this is a blog post by an anonymous author on LessWrong, rather... (read more)

[-]JackH5y*170

I completely agree that it is absurd that the kind of content in the OP is not more widely publicized. This was my precise motivation for writing this post.

Unfortunately, there is no good 'where to start' guide for anti-aging. This is insane, given this is the field looking for solutions to the biggest killer on Earth today.

The closest approximations to a 'where to start' guide for anti-aging would be:

That said, none of the above communicated all of the ideas that I wished to communicate in the OP in a succinct way. Again, this is precisely why I wrote it.

It seems to be one of the better introductions out there, as those in touch with field on the longevity subreddit seem to have appreciated my introductory guide, as it's one of the top-rated posts in the past week and has been given 5 awards. As an aside, I'm planning on turning this into a sequence, so if you have ideas for future topics please let me know.

I totally agree regarding funding for 80k equivalent sites. If someone wants to provide ... (read more)

4Yoav Ravid5y

I think mentioning your qualifications at the start (or at least the end) of the post would help. i wondered about it myself as i was reading it, and i would have been glad to read them if they were mentioned (instead of, say, feeling like it's bragging).

3JackH5y

Sure - I've just added that at the bottom. Thanks for the tip.

1David_Kristoffersson5y

Low hanging fruit intervention: Create a public guide to that effect on a web site.

6JackH5y

Completely agree - we have this planned on our Oxford Society of Ageing and Longevity website (ageingandlongevity.com). I also plan to write a sequence on LessWrong of perhaps 10-15 posts similar to this one. Feel free to comment if you think there are specific angles you'd like me to focus on (e.g. explaining the science in more detail, discussing common philosophical objections, describing the financing of longevity biotech, etc.).

2Felix Karg5y

Thank you for writing this, it was very helpful to me. I will read up on a number of links you provided in the post itself and other comments. I'm starting to dabble in Biology since last Semester (Computer Science Bachelors, currently doing Master’s degree) as a minor, some of my current interests are: * Epigenetics Especially related with newly available computational methods and experiments doable with CRISPR-modifications. What are the active areas of research? * Simulation Particularly of biological pathways or other relevant parts. What is commonly simulated? To what degree? * Measuring How easy it is to measure the 'Hallmarks of Aging', and how accurate are their relative predictions? What other measurements would be great to have (soon)? For me, it is not ultimately clear that they are relevant for the field at all, so bear with my selfishness here. I would especially be interested in a (slightly more technical) introduction to the current state of the Art, active areas of research, how it is related to anti-aging research, and how to learn more about each of them. Furthering anti-aging-research/awareness is actually a secondary career goal of mine, the first/current one is figuring out how to consistently raise the sanity waterline in organizations. It might even be possible to fulfill both at one organization, we'll see.

8Victorel Petrovich5y

I've been following the anti-aging field for almost 7 years: research news, overview articles, reviews etc. I don't know the author of OP, but I can say that the article he wrote here is as good as it gets (one of the best I've ever read), and, up to date. So are the recommendations he makes for further learning/immersion. I happen to have read many of the articles he cites, and they are all of very good quality. The names he cites (A. De Grey, Sinclair, Barzilai and others) are stars in this field, mentioned in most other anti-aging blogs as well. IMO, the kind of background this author has (not exactly working in aging research, but still within biology and familiar with research in general) is great for writing an overview like this: because it is less biased in terms of a preferred theory and approach for anti-aging - unlike (to various extent) reviews written by a star researcher in the field. Even this author has a preference (SENS) (but perhaps for a good reason, you'll have to judge yourself). So, the pointers given here are all great (just reddit/r/longevity alone will give you as much immersion and leads as you want). Personally, I read/follow some of the sources he recommends, and also follow this blogger https://joshmitteldorf.scienceblog.com .

2JackH5y

Thank-you for the kind words! Stay tuned for more articles like this one coming soon.

[-]DirectedEvolution5y130

I'm preparing for graduate school in tissue engineering via bioprinting. I was motivated by these considerations.

My sense is that ageing is both an evolutionary response to cancer and an entropic inevitability. No matter how much you supplement the body, eventually deleterious mutations will accumulate. The complexity of cellular systems makes them very difficult to improve on.

The strategy I envision is that we'll learn how to manufacture healthy, fresh tissues and organs from the recipient's own cells. While it's very hard to improve on the cell's natural mechanisms, we can harness it in this way to rejuvenate at the level of tissues and organs. People will receive periodic transplants of fresh organs built from their own cells.

[-]JackH5y*120

(1) Aging is not entropy (second law of thermodynamics). In fact, both young and old individuals are in very high entropic states, and it is not entropy that kills people when they die of aging. Instead, it is the accumulation of biological 'damage' (i.e. hallmarks of aging) described in the original post. If aging was inevitable due to entropy it would be impossible according to the laws of physics for biological organisms such as the hydra and tortoise to display negligible senescence, and for sharks to achieve the 400+ lifespans that they do without any increase in mortality risk.

(2) Your description of 'deleterious mutations' is accurate - genomic instability which includes DNA damage (as well as chromosomal rearrangement) is one of the 9 hallmarks of aging. But like all of the hallmarks, it is something we can attenuate. There are currently clinical trials for several DNA repair therapies such as nicotinimide mononucleotide (NMN), an NAD+-precursor molecule in Sinclair's lab at Harvard, and nicotinomide riboside (NR) which is being developed by the biotech company Chromadex.

For a good primer on genomic instability, I encourage you to read this article from Lifespan... (read more)

4DirectedEvolution5y

Thanks for writing the OP and for your response, I now see you mentioned this in the original. I’m excited to check your links out. Other commenters mentioned that an issue to anti-aging research in humans is the regulatory barriers. Part of the reason I’m interested in tissue engineering is that it may circumvent that issue to some extent. You can do your research relatively freely on tissue until you’re able to replicate a certain organ, test it on people who need a transplant, and “patch together” an approach to life extension in this way.

4JackH5y

Great to hear you are interested in contributing! I wasn't precisely sure about the anti-aging applications of tissue engineering, so I asked a colleague and this is what he said: So, it definitely seems important!

5Victorel Petrovich5y

I think the direction you've chosen, tissue engineering, will be very useful. One important organ for aging to be rejuvenated/replaced is thymus, whose degeneration is a major cause of declining immunity with aging. "No matter how much you supplement the body, eventually deleterious mutations will accumulate." yes, however, in nature, deleterious mutations don't accumulate in all species. Hydra is an example/exception. It replaces its cells at such a fast rate, that this is an important reason why it doesn't accumulate mutations (and other damage) and manages to be biologically immortal. In fact, the direction you've chosen for research would do the same but at the level of tissues/organs, not cells.

[-]Radford Neal5y100

It would be great if the mouse results turn out to apply to humans as well, but I have my doubts. These doubts are based on what I thought were pretty conventional biological assumptions, but that nevertheless don't seem to be addressed in the anti-aging discussions I've seen.

The basic problem is that there's a good reason mice don't live long. Even if they didn't age, the environment in which they live means they are very likely to die in a few years from starvation or predation. So genes that keep them from aging won't be selected for because of either or both of two reasons: (1) The selective advantage of not aging, when you're likely to die young anyway, isn't enough to overcome random mutation that undoes the anti-aging genes. (2) The advantage of not aging comes at some (possibly rather small) cost in terms of increased likelihood of death from predation or starvation, or decreased fecundity early in life. (For instance, it might have an energy/food cost, or might come with decreased physical performance, such as in running speed.)

Humans live in a different environment, in which slower aging is more advantageous. And indeed humans age much slower than mice, ... (read more)

3JackH5y

You are correct that interventions in mice do not always translate well to humans. Fortunately, several human trials have already shown that aging can be reversed. Time will tell how many of the current anti-aging approaches that have worked in mice will translate to humans. This comment doesn't make a lot of sense to me since mice used in the lab for lifespan studies are not subject to evolution today - rather, specific strains used for different kinds of experiments are purchased from specialized laboratories, where they are selectively bred. I don't agree with this. Senescent cells (one of the 9 hallmarks of aging) for example accumulate both in humans and mice with older age, and contribute to age-related tissue and organ dysfunction in both. Senescent cells by definition are apoptosis-resistant, meaning they are resisting the mechanisms (found in both mice and humans) to remove them. Hence, senolytic drugs extend lifespan in mice and probably humans by removing these cells, since the machinery in the body is unable to. Following on from my previous comment, your comment here is not true. The most promising strategy to slowing aging is not overly complicated in principle, even though it is a technical challenge - it simply involves routinely repairing the damage associated with the hallmarks of aging as they emerge. This can be done even if the precise causes of that damage (from normal metabolism) are not known. I suggest you learn more about the field by watching some talks on YouTube by David Sinclair, Brian Kennedy, Judith Campisi, Aubrey de Grey, Nir Barzilai, Joao Pedro de Magalhaes or any other of the speakers here to give you a better idea of the field of research.

[-]Eli Tyre5y90

Random question: Why is there such a large difference between the life extension results for mice vs. for rats. Naively, they seem like they're pretty similar.

Are we trying different kinds of treatments on one than the other for some reason, or is it just much harder to intervene on rat life-spans?

3johnswentworth5y

My understanding is that the usual lab mouse breeds are highly inbred, resulting in high levels of cancer. That makes is "easier", in some sense, to extend their lifespans - especially by interventions which trade off cancer risk against other age-related deterioration. For instance, there are ways to make cells more sensitive to DNA damage, so they undergo senescence at lower damage levels. This can decrease cancer risk, at the cost of accelerating other age-related degeneration.

[-]Natália5y90

[F]ew members of [LessWrong] seem to be aware of the current state of the anti-aging field, and how close we are to developing effective anti-aging therapies. As a result, there is a much greater (and in my opinion, irrational) overemphasis on the Plan B of cryonics for life extension, rather than Plan A of solving aging. Both are important, but the latter is under-emphasised despite being a potentially more feasible strategy for life extension given the potentially high probability that cryonics will not work.

I think there is a good reason for there be... (read more)

[-]JackH5y*230

I agree that the LessWrong community can have a positive impact on the cryonics field by signing up for cryonics and direct more capital in to this extremely under-funded field. Cryonics is especially relevant for people older than 40 today who are much less likely to make it to longevity escape velocity.

However, I disagree that (1) there is barely anything people can do now to slow their aging and (2) there is barely anything that the average person can do to support the research and development of anti-aging therapies. I plan to write a separate post covering these points, but I'll provide a few thoughts here.

Regarding (1), there are a multitude of actions you can take now to slow your aging and risk of age-related diseases (disclaimer: NOT a substitute for medical advice):

Non-pharmacological:

Exercise - attenuates many hallmarks of aging
Intermittent fasting - improves metabolic switching and cellular stress resistance
Maintain strong social ties - social relationships are a strong predictor of lifespan
Overcome depression, which accelerates biological aging
Optimize your circadian rhythm
Take a biological age test such as myDNAage or InsideTracker and monitor your age over time.

... (read more)

8Matthew Barnett5y

The personal strategies for slowing aging are interesting, but I was under the impression that your post's primary thesis was that we should give money to, work for, and volunteer for anti-aging organizations. It's difficult to see how doing any of that would personally make me live longer, unless we're assuming unrealistic marginal returns to more effort. In other words, it's unclear why you're comparing anti-aging and cryonics in the way you described. In the case of cryonics, people are looking for a selfish return. In the case of funding anti-aging, people are looking for an altruistic return. A more apt comparison would be about prioritizing cryonics vs. personal anti-aging strategies, but your main post didn't discuss personal anti-aging strategies.

8JackH5y

Both are important. Anti-aging is unique in the following way: since all of us are slowly dying of aging, it's in our best interest to want the field progress for selfish reasons, but also our altruistic interest for society to solve aging as soon as possible, as this saves millions or billions of human life years. On a personal level, maximising the probability of reaching longevity escape velocity is a min/max problem with two important variables: (1) maximising personal lifespan, by adopting personal longevity strategies (2) minimising the time until society reaches longevity escape velocity by helping to progress the longevity field. You can think of it as a 'race against time' - to live forever (or at least, a very long time) one has to live in the subset of worlds which represents the intersection of society achieving longevity escape velocity, and one living long enough to make the cut, to avoid being among the last generations to die. Personal longevity strategies are important, since a few years of additional life from longevity strategies could be the difference as to whether one makes it to reach longevity escape velocity or not. I suspect that many baby boomers may, unfortunately, miss the cut, but many Millenials and Gen Z's could make it, particularly if they are proactive with longevity strategies. Progressing the field is also important, as living to 150 with personal longevity strategies doesn't mean much if you fall 5 years short of reaching LEV because timelines were too long, for example. Now, as to which is more important - personal longevity strategies or progressing the field - it's unclear. Aubrey de Grey in his recent interview with me stated that the latter is much more important, since future therapies will vastly improve healthspan more than anything we can do today, and thus bringing these therapies into the world as soon as possible is the main priority for those who wish to make it to longevity escape velocity. This would sug

1deskglass5y

If Brunemeier's PDF's is something you can share, I'd like to read it.

2JackH5y

Here's some of the important stuff (not medical advice, obviously): Daily multivitamin Omega 3 fatty acids (EPA/DHA) Magnesium citrate Turmeric (curcumin) Resveratrol / pterostilbene Metformin / berberine Apigenin Quercetin NR (nicotinamide riboside) EGCG (green or white tea) Ocimum sanctum (Tulsi) Bacopa monnieri (standardized 20% bacosides) Gotu Kola (Centella asiatica) Gingko biloba B12 – many people are deficient Vitamin D (get blood tested to optimize, ideally 30 min/day full sun, 2000 IU) Vitamin C (megadose, 5 g / day +, spread throughout the day) Piracetam + Choline Uridine Acetylcarnitine + N-acetyl cysteine Glycine Supergreen/superfruit blend*: “Blender Culture” .

1Synaptic5y

I strongly support anti-aging research. I'm not clear on what your criticism is of cryonics. Perhaps I missed where you explained why you think that cryonics will not work? For example, where in the Drake equation does your probability differ from Steve Harris's or Mike Perry's? Also, you point out the large number of organizations and companies involved in aging research. Surely the fact that there are way fewer in cryonics means that it is has merit from an underfunding perspective?

1JackH5y

The estimates of Harris and Perry that cryonics doesn't work range from 23% to 99.8% - which are potentially quite high (as I phrased it in the OP). Cryonics might work, but there's a potentially very good chance that it doesn't. I agree that cryonics is underfunded even more than aging research. It seems likely that an increase in funding to cryonics could increase the probability that cryonics works, by improving the chance of success of the following variables: * Favorable conditions for suspension * Suspension preserves enough information * Mishap-free storage * Nanotechnology is perfected * Cryonic revival is "cheap enough" At the very least, it would help to reduce the uncertainty regarding some of the parameters, providing as a clearer picture of the feasibility of cryonics. However, several of the parameters would be likely to be unaffected by increased funding: * Materialism is correct * Identity encoded in structure * Sufficient social stability * Cryonics is continuously legal * Nanotechnology is physically possible * Cryonic revival is permitted Ideally, both cryonics and anti-aging would receive more funding. The intention of my post was not to encourage reductions in funding into cryonics; rather, to increase awareness among LessWrongers readers about anti-aging.

1Synaptic5y

On the contrary, I very much expect that more funding would help with these factors. The success of cryonics is limited by sociopolitical factors, and the more people who have buy-in, the more likely people are to be protected when in long-term cryopreservation. This is an admirable goal. =)

1JackH5y

Yeah, that seems likely. Certainly 'the social problem' (which combines several of the parameters) in general will reduce in likelihood the more funding cryonics receives.

[-][anonymous]5y90

Regarding cryonics not working: this depends on your definition of 'working'. Let me describe the problem succinctly.

Assume at some future date you can build a 'brain box'. This is a machine, using some combination of hardware and dedicated circuitry, that is capable of modeling any human brain that nature could build. It likely does this by simulating each synapse as a floating voltage, modulated by various coefficients (floating point weights) when an incoming pulse arrives.

Well, you can choose randomly the weights, and assuming ... (read more)

4JackH5y

Hi Gerald, In the original article, I linked to Alcor's calculation of the probability that cryonics works. It ranges from 0.2-77% and this calculation is based on the 14 variables below: 1) Materialism is correct 2) Identity encoded in structure 3) Favorable conditions for suspension 4) Suspension preserves enough information 5) Mishap-free storage 6) Cryonics organization survives 7) Sufficient social stability 8) Cryonics is continuously legal 9) Nanotechnology is physically possible 10) Nanotechnology is perfected 11) Nanotechnology is non-catastrophic 12) Cryonic revival is "cheap enough" 13) Cryonic revival is permitted 14) The social problem Depending on your probabilities for these variables, the estimation of the overall probability that cryonics will work overall will vary.

2magfrump5y

Even 0.2% seems quite optimistic to me. Without going into detail, anything from 3-8 seems like it could be 10% or lower and 12-14 seem nearly impossible to estimate. I wouldn't be surprised to find my personal estimate below one in a million.

3JackH5y

Yeah. For your interest, here are the calculations from Alcor: Steve Harris, MD: 1) Materialism is correct: 0.95-0.99 2) Identity encoded in structure: 0.95-0.99 3) Favorable conditions for suspension: 0.75-0.95 4) Suspension preserves enough information: 0.50-0.90 5) Mishap-free storage: 0.95-0.99 6) Cryonics organization survives: 0.20-0.60 7) Sufficient social stability: 0.70-0.90 8) Cryonics is continuously legal: 0.70-0.90 9) Nanotechnology is physically possible: 0.90-0.98 10) Nanotechnology is perfected: 0.95-0.98 11) Nanotechnology is non-catastrophic: 0.20-0.50 12) Cryonic revival is "cheap enough": 0.85-0.95 13) Cryonic revival is permitted: 0.50-0.80 The social problem is non-catastrophic: 0.008-0.18 Technologically, will cryonics work? 0.29-0.81 Overall, will it work? 0.002-0.15 That is, a 0.2-15% probability that cyronics works overall. Mike Perry, PhD: Note: his calculation lumps 7 of the 13 parameters as 'the social problem' which he calls condition n. 1) Materialism is correct 1.00-1.00 2) Identity encoded in structure: 1.00-1.00 3) Favorable conditions for suspension: 0.75-0.95 4) Suspension preserves enough information: 0.50-0.90 5) Mishap-free storage: 0.90-0.99 6) Cryonics organization survives: n-n 7) Sufficient social stability n-n 8) Cryonics is continuously legal n-n 9) Nanotechnology is physically possible 1-1 10) Nanotechnology is perfected n-n 11) Nanotechnology is non-catastrophic n-n 12) Cryonic revival is "cheap enough" n-n 13) Cryonic revival is permitted n-n The social problem is non-catastrophic: 0.39-0.86 Technologically, will it work? 0.34-0.89 Overall, will it work? 0.13-0.77 That is, a 13-77% probability that cyronics works overall.

2magfrump5y

Yeah I think my main disagreements are 4 and 5. Given stories I've heard about cryonics orgs, I'd put 10-50% on 5. Given my impression of neuroscience, I'd put 4 at 25-75%. Given that I'm more pessimistic in general, I'd put an addition 2x penalty on my skepticism of their other guesses. That puts me around 0.01%-20% spread, or one in ten thousand lower bound, which is better than I expected. If I was convinced that a cryo org was actually a responsible business that would be enough for me to try to make it happen.

1JackH5y

Yes - it's hard to perform the calculations and end up with a high probability that cryonics works. I think cryonics overall is much less feasible than many Less Wrongers tend to assume. Overall, I think anti-aging has a much higher chance of working to keep us alive much longer than cryonics does.

[-]niplav4y70Review for 2020 Review

I read this post at the same time as reading Ascani 2019 and Ricón 2021 in an attempt to get clear about anti-aging research. Comparing these three texts against each other, I would classify Ascani 2019 as trying to figure out whether focusing on anti-aging research is a good idea, Ricón 2021 trying to give a gearsy overview of the field (objective unlocked: get Nintil posts cross-posted to LessWrong), and this text as showing what has already been accomplished.

In that regard it succeeds perfectly well: The structure of Part V is so clean I suspect that it... (read more)

[-]habryka5y60

Promoted to curated: I've been meaning to follow up on the state of anti-aging work for a while, and this was really a quite good overview. I also know of a number of other people who found it useful. Thank you for your work when compiling this overview!

2JackH5y

Thank you very much, I appreciate it. This is only a short introduction to the field, and I plan to write several follow-up articles in the near future to create a larger sequence (covering: aging and COVID-19, the ethical arguments for/against anti-aging, aging and cancer, and more anti-aging therapy approaches).

[-]ChristianKl5y60

For personal longevity strategies, I recommend talks by Dr Rhonda Patrick, Dave Asprey and Dr Peter Attia.

Dave Asprey is a person who claimed to increase their IQ by 40 points without engaging in any effort to measuring his IQ by taking the best results found in p-hacked trials for interventions and adding them up. I think that was even before he went into business as a supplement salesman.

More recently he argued that he believes in reincarnation because it helps him to lower his stress levels.

He references a lot of research, but I don't... (read more)

8JackH5y

Dave Asprey's book, Superhuman is pretty good - it explains the hallmarks of aging in simple terms and provides generally good advice for limiting the damage associated with the hallmarks. He draws upon a lot of scientific literature, and has over 400 academic references. Asprey does a good job synthesising the research into practical steps a person can take to lower their rate of biological aging - something that most of the researchers in the field don't have the time to do. A few things are a bit wacky, but in general I'd say 95% of the advice he says is pretty good, and the other 5% won't do any harm. Dave Asprey is a pioneer of the longevity biohacking community, and runs a supplement company called bulletproof. But, if you don't like his advice, then you can look towards Rhonda and Attia. Dr Rhonda Patrick has a PhD in cell biology and is extremely knowledgeable about aging and longevity - just watch her interviews with David Sinclair, Valter Longo or Steve Horvath - all big names in the field. She talks to them on the same level since she knows the literature very well. Dr Peter Attia is an MD who is also very clued up on the aging field too, and on his podcast has also interviewed many big names such as David Sinclair and Nir Barzilai. I recommend this talk of his as an introduction to some important concepts in aging. David Sinclair's book Lifespan is also the gold standard for personal anti-aging strategies, which are summarised here.

[-]thomas95y50

Hi, I was a talk at a conference, in 2019, that mentioned that many new breakthroughs in cancer research were down to improvements in the accessibility of data science, and large scale computing.

As a Software Engineer, is there any way I can contribute these type of skills towards longevity research? The only avenue I could find was to get a job at Calico, but realistically, I'm half a world away in Ireland.

5Victorel Petrovich5y

Just of the top of my mind: an example lab that makes (relatively heavy) use of computational approaches is that of J.P. de Magalhaes (U.of Liverpool, so not too far from yourself). More generally, I believe many labs nowadays could use the help of a software engineer. You could read more on aging research (this article has great links, AFAICT), choose a direction, a lab, and ask them if you can help them. I might to the same, one day.

4JackH5y

Hi Thomas, Great to hear you are interested in contributing to the field! You can have a look at LongevityList.com and see if there's anything on there. It's a new project so I'm not sure how regularly it's updated. Alternatively, you could join the Longevity Subreddit and the Lifespan Discord server and ask there, as there are many people involved in the field there willing to help. Often, people like yourself will ask about job opportunities and get connected with opportunities. Hope that helps!

[-]AM5y40

Love this article.

After reading the The Fable of the Dragon-Tyrant a few years ago after my father died, I went into a deep dive on this and ended up making a calculator, comparing the impact of eliminating various causes of death on average / median lifespan. It's very simplistic, but I found it interesting to use to illustrate how ageing contributes to death:

http://life.analogmantra.com/

2jmh5y

Very interesting. Assuming we eliminated everything but accidental causes looks like we should live to about 120+ years. I think Sinclair had said that was the expected lifespan as well. Taking the tool at face value, it seem that both personally and socially effort focused on circulatory diseases should give the biggest bang for the buck. Then again I didn't run through different cases of combination so...

2CronoDAS5y

If the actuarial statistics I've read are accurate, about 1 in 1000 18 year old men in the US die before their 19th birthday. If the chance of dying each year stayed perfectly flat, life expectancy would be about 1000 years...

3JackH5y

Some have calculated lifespan would be 2800-8900 years on average without aging. https://www.iii.org/fact-statistic/facts-statistics-mortality-riskhttps://math.stackexchange.com/questions/3044194/whats-the-average-life-expectancy-if-only-dying-from-accidents

1AM5y

True, circulatory diseases would be a big win, but do you think the marginal buck there is likely to do as much as a marginal buck focused on aging giving the amount of funding allocated to each? If we add the R&D budgets focused on circulatory diseases to the treatment cost of circulatory diseases (potential profit pool for pharma companies), my intuition says that the number would be ~20-100x the total amount of funding to aging-stopping or -reversing technology. What do you think the ratio would be?

2JackH5y

Really love the app, great work! Just a bug I found (I think it's a bug?) - if I untick all the boxes, the median age of death goes to 0.

1AM5y

Definitely a bug! It was my first and only foray into D3.js so there are a lot of bad states you can get into fairly easily. Might rebuild it in something else one day.

3JackH5y

I think it would be worth rebuilding if you have time. If you do, make sure to share it on Longevity Subreddit. You will get a lot of interest in it there.

[-]DirectedEvolution5y40

Here's a Peter McCluskey review on "age later" from back in October.

[-]Alexey Lapitsky5y40

Thanks for an amazing post, Jack!

I think it's worth mentioning that damage accumulation as the root cause is not the consensus view anymore.

To quote Josh Mitteldorf, there are three views:

(from the “programmed” school) Aging is programmed via epigenetics. The body downregulates repair mechanisms as we get older, while upregulating apoptosis and inflammation to such an extent that they are causes of significant damage.
(from the “damage” school) The body accumulates damage as we get older. The body tries to rescue itself from the damage by upregulating repai

... (read more)

3JackH5y

Hi Alexey, So, having talked to a number of people in longevity biotech, I'm skeptical as to whether view (1) i.e. Sinclair's 'information theory of aging' which posits epigenetic aging is the master regulator for the other hallmarks is accurate, and that cellular reprogramming alone is sufficient to slow aging. I think the information theory of aging is good PR for the field, but I don't think it's entirely correct. Still, the next 5 years of research will provide more clarity as to the relationship between epigenetic alterations and the other hallmarks of aging. I hope (1) is true although from the data I've seen and people I've spoken to behind the scenes, I don't think it's likely that cellular reprogramming alone will be enough. I think the hallmarks develop to some extent independently, even though there is some level of cross-talk between them, and will have to be individually addressed.

1Alexey Lapitsky5y

Very curious to hear a bit more about why you are skeptical about epigenetics and information theory of aging as the primary cause. But I completely agree that it's not the only cause! "Being sufficient to slow aging" is a pretty low bar, I have virtually no doubt that reprogramming will slow aging (it already has been done experimentally with mice).

4JackH5y

I don't see a lot of evidence for the information aging theory in the literature, and most geroscientists don't seem to think that epigenetics is the master regulator of the other hallmarks. This isn't to say it's not true, just that there's insufficient evidence at this point. Sinclair discusses all of the hallmarks, but focuses on epigenetics as the most important - which is incidentally the one he studies. Bear in mind as an academic this is something are incetivised to do - to tell a narrative that fits their research agenda, to attract funding. Looking at the field as a whole, there is consensus about the hallmarks but not so much consensus about the information aging theory, and in fact I don't know of any other major geroscience researchers who have endorsed the information theory of aging. It's too early to say that he's incorrect, but the theory seems unlikely from my reading.

1Alexey Lapitsky5y

Interesting, thanks! My thinking is that: 1. Methylation increases with age and predicts biological age 2. Methylation affects protein synthesis in a semi-random way Those points mean that epigenetics at least partially causes all hallmarks dependent on protein synthesis (loss of proteostasis, intercellular communication, etc). Meaning that epigenetics is at least partially upstream of at least a few hallmarks. Not sure what being correct about information theory of aging would exactly mean or what other evidence to expect. Intuitively it feels that our efforts should focus upstream and that there are more low hanging fruits in epigenetics than in most of the other hallmarks.

1JackH5y

That seems plausible! The only thing I'll say is that from what I've heard, epigenetic reprogramming in vivo may be particularly challenging in many tissues in the body. Therefore, I suspect mTOR inhibitors and senolytics may be lower hanging fruit for anti-aging therapies approved first.

[-]avturchin5y40

There is a problem with most anti-aging interventions: long expected duration of human trials, as results and lack of side effects will be obvious only decades after the start oа such trials. Without trials, FDA will never approve such therapies.

However, there is a way to increase the speed of trials using biomarkers of aging - or testing of already known to be safe interventions, like vitamin D. But biomarkers need to be calibrated and safe interventions provide only small effects on aging. Thus, it looks like some way to accelerate trials is needed if we want radical solution to aging to 2030. What could it be?

7JackH5y

Yes, we need improved biomarkers of aging. Once we have biomarkers that are accurate enough to detect changes in aging or anti-aging over the course of months, it will be much easier to obtain high-quality data for prospective anti-aging compounds. Another solution that aging researchers have discussed is developing frameworks for decentralized clinical trials that could bypass institutional approval but still produce credible results. There also needs to be a paradigm shift in society, biomedical research, and regulatory bodies like the FDA to recognise and classify aging as a disease. Open science which aims to make all science accessible to everyone, whether amateur or professional, is would also help to accelerate the rate of research.

2pjeby5y

Any pointers on what to search to find more info on this from actual research? I wasn't aware that vitamin D was considered to have anti-aging properties, or that there was much consensus on its safety.

5JackH5y

For a good summary video on vitamin D and aging, I recommend this. For academic papers and other articles, I recommend this, this and this. For information on personal longevity strategies, I recommend the following: - Watching videos by Dr Rhonda Patrick, Dr Peter Attia and Dave Asprey - Joining Facebook biohacking groups such as this, and this. - Joining the Lifespan discord server and reading comments on the 'personal longevity strategies' channel.

4avturchin5y

It is safe enough to be sold OTC, and there are some research which connects with life extension effects. The real problem is that we don't have human tests of its effects on longevity, despite its widespread use. The first study like this will be TAME, which will explore life extension properties of metformin. There are several reasons why such studies are difficult to perform. Firstly, they are costly, but known safe things are non-patentable. Secondly, they need to be very long., and long human studies are especially costly.

1Yoav Ravid5y

Another option is to advocate for emergency authorization for old people.

2avturchin5y

Unfortunately, it seems that most intervention works before aging actually developed, so we need to give them to younger people, at least before 50.

4JackH5y

This is not true. Aging doesn't develop, rather, it is an ongoing process of damage accumulation (i.e. hallmarks of aging) that occurs as a by-product of metabolism, explained in the original post. Aging occurs in both young and old people, although the rate of aging accelerates as diseases of aging develop. Reversing the damage associated with the hallmarks of aging at any chronological/biological age is likely to improve their phenotype and expected longevity. The more advanced the anti-aging technologies become, the better equipped we will be to reverse large amounts of damage associated with advanced age. That said, there is no reason to think that there is a cliff after which aging cannot be reversed.

3avturchin5y

That is true for therapies which work on damage (SENS). But if we see aging as a process which creates the damages, than it is reasonable to stop it on early age. Also, I've seen a recent article "Longevity‐related molecular pathways are subject to midlife “switch” in humans" which implies that many interventions should happen early in life. Thanks for great post!

4JackH5y

Evidence in mice studies does indicate that earlier therapies (for example of senolytics) do facilitate greater life extension. However, with better anti-aging technologies the 'switch' (from the paper you refer to) could theoretically be reversed, as there's no biological law that would prevent restoring a phenotypically older individual back to a more youthful state.

1Yoav Ravid5y

I see. in that case perhaps we would need emergency authorization for anyone who needs it to stay within escape velocity timeline. though that definition is too complex for me to see a scenario where FDA approves it (at least not without massive pressure).

3JackH5y

Yes, I hope regulators will give older individuals who are soon to die of aging the option to have access to more radical life-extension therapies.

[-]RobertM5y40

Minor correction: the metformin trial study (TAME) is not currently underway; they are still waiting for the FDA to designate aging as an "indication" to be treated (and also raising funding).

Good writeup, though, thanks!

4ChristianKl5y

It got the necessary approval in 2015 and in 2019 a rich private individual seems to have given them the missing 40$ million to run the trial: https://www.longevity.technology/worlds-first-anti-aging-trial-gets-green-light/ and the plan was to start the trial at the end of 2019. It might very well be running currently. Maybe someone else has more info?

1RobertM5y

Oh, interesting, thanks for the correction! I was just going by their website (linked in the OP), which may not have been updated since 2015(?!).

[-]Rune5y30

Besides donating money to SENS, is there any way for people with money to help speed up this research? Specifically, are there companies that one can invest in to help this research? Say if you're in charge of a lot of investment money (maybe you're a fund manager or ethical investment advisor or something) and want to make investments that make the world a better place. Anti-aging sounds like it would be a great place to invest some of the financial capital available. How would one do that?

6JackH5y

Copied from the response to another, similar, comment: There are a number of publicly-traded longevity biotechnology companies. You could invest in Unity Biotechnology (NASDAQ:UBX) or Proteostasis Therapeutics (NASDAQ:PTI), for example. I also recommend the Longevity Market Cap newsletter. Here are some links that may be useful: https://investoraccess.masterinvestor.co.uk/events/investing-in-the-age-of-longevity/ https://transhumanplus.com/investments-on-antiaging/ https://investingnews.com/daily/life-science-investing/longevity-investing/longevity-research-companies/ https://www.nanalyze.com/2019/08/top-10-companies-longevity/

1Florin5y

Aging Biotech Info https://agingbiotech.info LongevityList (companies search) https://longevitylist.com/explore/?type=company&sort=latest

[-]danhite5y30

In part 1 is this error:

"This equates to 37 million people - a population the size of Canada - dying per day of aging."

Fix: change "day" to "year"

3JackH5y

Fixed, thanks!

[-]Shmi5y30

Do we understand why cats live longer than dogs?

1Mo Putera2y

I'm curious, where were you going with this in the context of this post's anti-aging SOTA approaches?

2Shmi2y

I guess for me it's a test of understanding the role of genetics in aging. If you cannot answer this question, you cannot hope to extend the duration of the non-senescent part of human life.

[-]ArtMi3y20

I may argue against the anti aging field (and probably now that i reflect about it, it seems more important than most non-essential productivity in society) that it is highly more probable that we reach an agi singularity during our lifetimes, before we die of aging. (depends on your age).
What do you think?

5gwern3y

"Why not both?" If you have spent any time reading anti-aging & AGI literature, it's clear that there is minimal funging: just not much overlap of funders, researchers, or hobbyists. Most of the people doing anti-aging research have little interest in AI and vice-versa, even if there are many people who are interested in both, they represent only a small fraction of the people interested in just one. Most of the money not spent on anti-aging won't go to AGI safety but something else entirely, and vice-versa. And if all the AI stuff ultimately whimpers out, as is still entirely possible, then you will be very glad that anti-aging research continued. Biology research tends to not be amenable to "throw lots of money at it at the last minute".

2Vaniver3y

I feel like there is some? Like, I'm in the overlap, kind of, Nick Bostrom wrote The Fable of the Dragon Tyrant, cryonics / brain preservation is kind of like anti-aging, and so on.

8gwern3y

There is some, but I think we greatly overestimate it in these circles. Go over to, like, Longecity or /r/longevity, or read comments to David Sinclair stuff. If you were to judge by LW comments, you might think that the funging factor is, like, >90%. "Obviously pretty much everyone concerned about AGI is also concerned about aging and vice-versa! Certainly everyone I know seems to be! How could you not be?!" Whereas I think it's closer to, say, <10%. Either concern has a very low base-rate, so despite the enrichment, you still wind up with by far the absolute majority of people in AGI not being all that interested in anti-aging and vice-versa - such that if one area were zeroed out, it would barely improve funding or participation in the other. AGI people wouldn't go work on anti-aging, they'd go work on, I dunno, cryptocurrency.

2Vaniver3y

Oh, yeah, sorry; I don't believe the "and vice-versa" bit and if that's what you're pointing out, I agree.

1Florin3y

The probability of dying of aging is 100%. The probability of dying of AGI is less than 100%. The probability of the development of anti-aging tech via non-AGI means is close to 100% (e.g., senolytics). The probability of the development of anti-aging tech via AGI is not close to 100%. Therefore, some of us prefer to focus more on aging than AGI.

4Vaniver3y

Surely if I die of something other than aging, I don't die of aging?

1Florin3y

Sure, I could have added the caveat "if you don't die of anything else first (and most people won't)," but I wanted to keep the caveats to a minimum. Perhaps a general caveat would be that these statements should be understood to apply to most people alive today. About two thirds of deaths are caused by aging (100k out of 150k per day) and in the developed world, it's 90%.

[-]Yoav Ravid4y*20

I don't have the skills nor the time to review this post properly, but I think it's very good and it helped me understand the state of the art of anti-aging, so I think it should be part of the review.

[-]CronoDAS5y20

Science fiction author and physicist David Brin has pointed out a theoretical reason why we might expect anti-aging therapies that work in mice to fail in humans: the human lifespan is already a ridiculous outlier. Life spans vary with size, metabolism, and other factors, but one thing tends to hold constant: most mammals have a lifetime of about one billion heartbeats. Humans get a whopping 2.5 times that. An intervention would have to more than double a mouse's lifespan just to catch up with whatever it is that evolution has already done to humans - if there are any simple mechanisms that can cause a mammal's body to increase its lifespan, humans are probably already pushing them to their limits.

4JackH5y

If you're referring to median lifespan, we already know that many factors increase lifespan by up to 10-15 years in humans cumulatively: exercise, fasting, diet and so on. So it is highly likely that therapies (e.g. mTOR inhibitors) that potentially act through similar pathways will extend median lifespan. In terms of maximal lifespan, I'm not sure of the strength of those theoretical reasons in light of mechanisms of aging such as cellular senescence, which is known to strongly contribute to the aging phenotype in mice and humans and which can be removed in humans now (2020 study). Evolution is not optimizing for lifespan...only on gene transmission. So in general, I think arguments along the lines of 'as humans we are hitting our natural limit of lifespan' are poorly substantiated.

[-]Wedchidna5y20

Fellow humans, do forgive my newbieness, but I am surprised this following study has not been mentioned:
- https://www.aging-us.com/article/202188/text
I speak no chemics, so I might've lost something midway of the presentation. Yet, since I have celebrated the aforementioned article as my most cherished 2020 article, I've guessed the chance of it cherishing someone's day upward was worthy of the hereby mentioning. I shall read replies probably: in case I take time to do so, one may consider oneself thanked for the reply, in advance.

2JackH5y

I did not include the Tel Aviv/HBOT study since it is not considered a promising approach to anti-aging by most researchers in the field. The conclusions of the study are potentially misleading, due to the highly improbable senolytic effect of oxygen therapy. In my recent interview with Dr Aubrey de Grey, I asked him about this same study (timestamp: 40:30), and he said that it was enormously over-hyped. I encourage you to read this article, which explains the media circus around the study, and critiques the science: https://www.lifespan.io/news/media-circus-surrounds-hyperbaric-oxygen-study/

[-]Marek Veneny5y20

I purely enjoyed the read about the State of the Art. I had no clue there's so much going on behind the scenes.

If I may, I would like to steer the discussion from technology towards ethical and practical matters.

The argument could go like this:

We're living on the cusp of technological progress. We (most western countries) enjoy easy access to more resources than we could ever consume and enjoy. The accessibility of the internet means we can communicate globally. We have cars and fridges and smart homes and Nicolas Cage pillowcases. Y... (read more)

[-]JackH5y160

Your comment alludes to 3 exceedingly common objections to anti-aging:

(1) 'Death and aging bring meaning to life'

(2) Distributional justice (i.e. 'only for the rich')

(3) Overpopulation (resource overconsumption, environmental impact etc.)

All of these objections have been responded to at length by David Wood in his book The Abolition of Aging, Aubrey de Grey in his book, Ending Aging and David Sinclair in his book, Lifespan and on blogs such as FightAging.org and Lifespan.io.

Anyway, I plan to write a Part 2 post covering the main ethical arguments including the three you reference, but will provide a short summary here:

(1) 'Death or aging brings meaning (or happiness) to life'

My point is this: Age and suffering give meaning to our lives. Technology slowly but surely eliminates both. Without any struggle - and as close to paradise as ever - where will we find meaning? In continuous progress? In "higher" quality of life?*

While chronological aging gives meaning to our lives, as existing over time allows to experience reality for longer (allowing for self-actualisation, building friendships and relationships, pursuing pass... (read more)

1Vanilla_cabs5y

I am not under the impression that physical comfort is what was opposed in Fight Club. After all, hunter-gatherers also accessed more resources than they could ever consume, like top-quality fresh air and sunlight. I think it was consumerism. Under consumerism, consuming is not driven by personal motivation, but by the external general goal of supporting the economy. Instead of being an end, the consumer has to be turned into a means to that single end, a slave to consumption, through ads and social pressure.

[-]Yves Dorfsman5y20

Mike Lustgarten's work should be added in the reference sections:

book: https://michaellustgarten.com/2016/11/18/microbial-burden-a-major-cause-of-aging-and-age-related-disease/
website: https://michaellustgarten.com/
twitter: https://twitter.com/mike_lustgarten

[-]ChristianKl5y20

When it comes to the idea of massively improving healthcare outcomes there seem to be two strategies. One is to focus on antiaging. The other is to focus on increasing our research capability by improving the tools we have available.

When Zuckerberg went out and interviewed heatlh care experts it seems they convinced him that tool building is more promising then object level research.

How strongly do you believe object level research on antiaging to be better then tool building? What's your argument for it?

7JackH5y

Developing platform technologies is important in pharma and biotech, and that's happening. But the limiting factor seems to be testing anti-aging drugs, and developing better biomarkers. There is no shortage of potential anti-aging therapies - there are hundreds waiting to be tested. The limiting factors are funding and researchers. We need more laboratories working on testing new therapies for anti-aging.

5jmh5y

I'm just wondering about the problems with funding and researchers. One would think that plenty of money is actual around but it's more about both awareness and some belief that a tangible return to the investors would be likely. That seems like it might be more a problem of asymmetric information as it were -- or perhaps a bit of "language" between the groups. What's your sense there? For research is there any structure that might work a bit like various gig-econcomy sites. Basically forums that work as an infrastructure to allow a wide audience of those capable of research/analysis to form quick teams to tackle a problem. Or perhaps just do some of the initial leg work to see if some line of thinking is actually going somewhere? I have the suspicion that perhaps a lot of the effort here might be less about lab work and more about digging though the results (but that may well be completely wrong). If both the above are kind of right and some type of open infrastructure that brings both together might be useful -- though also suspect there must be a bunch of incubator type structures already in place.

5JackH5y

You're 100% spot on here. 'Curing aging' and 'longevity' aren't common ideas in biomedical research, but 'curing cancer', 'curing Alzheimer's' and 'curing heart disease' are. This is unfortunate given aging is driving all of these conditions. It can sometimes be frustrating being in the longevity field, because researchers in other fields are incentivised to remain in their silos in which the core premises (e.g. curing cancer is good and effective) are treated as dogma, rather than see the bigger picture and work on solving the problem in more efficient ways. Once you suggest that slowing aging might be a more effective approach to extending healthy human lifespan, many researchers find it difficult to engage in the conversation. This is especially the case since education into the biology of aging is extremely poor in most biomedical and medical programs. Even in my case, I went through 5 years of tertiary education without learning the information in the OP. This information I gathered through speaking to experts in the field, reading books such as Lifespan, reading blogs like Lifespan.io and FightAging.org, reading thousands of papers on this topic and attending aging conferences. Still to this day, there are unfortunately very few channels educating people on the hallmarks of aging and the connection between these and the diseases of aging. Most cancer researchers I spoke to know very little about the hallmarks of aging, for example, and the connection between the hallmarks and disease. This is because their work focuses on solving the problem of cancer once it arises, rather than solving it in advance by curing aging. All of their incentives (grant funding, publication opportunities) are towards trying to cure cancer, rather than trying to extend healthy human lifespan (and delay the onset of cancer, potentially for hundreds of years) by slowing or reversing aging. This is unfortunate since, as I outlined in my post, aging is by far the biggest driver of

1Florin5y

And in the OP: Sometimes, focusing on one disease is necessary, like in the case of cancer. To reach LEV, the risk of dying from cancer would need to be zero. The only way to get there in any reasonable amount of time is to developed a way (like WILT) of dealing specifically with cancer.

3ChristianKl5y

While it's happening it's worth pointing out that the article you linked says "Given that pharma companies depend on innovation, science, and research and development, it may seem counterintuitive that they lag behind the digital curve. In McKinsey’s ongoing survey to measure companies’ “Digital Quotient,” the pharmaceutical industry ranks in the bottom third of industries measured." It doesn't happen as fast as it would be desirable. It's my impression that SENS focuses on doing basic research and not testing anti-aging drug candidates. If that's how you see the current bottleneck why recommend SENS and Lifespan.io over Lifespan Research Institute which actually focuses on testing anti-aging drugs? It could be that the problem of biomarkers is about doing a lot of measurement with our existing tools and looking for correlations. It could also be that we need tools that measure certain biometrics more accurately and cheaper then we currently can to progress. The position that we already have all the necessary measurement tools seems to me optimistic. If you hold it, why do you hold it?

2JackH5y

I encourage you to read the full article, not just the first paragraph. Specifically: SENS fund basic research that leads to new approaches to anti-aging drug development. Here is a good example of this. They sponsor both intramural and extramural research. Several longevity biotech companies such as Underdog Pharmaceuticals has been spun out of research funded by SENS. The longevity biotech companies then take the technology through clinical trials. I encourage you to have a browse of the research they have funded, here. LRI and SENS fulfil essentially the same role - to fund important research in this field, to increase the probability that effective anti-aging therapies will be discovered. I think LRI is also a good place to donate, though I am less familiar with their work.

2ChristianKl5y

There are two ways you can react to DeepMind making progress on protein folding. The one is to say: "Great there's progress". The other is to look at the inability of the existing companies to innovate. When Illumina started having their monopol on sequencing technology, the cost effectiveness of the technology suddenly stopped going down like is was before. After Theranos went bust we don't have new companies that go after cheaper blood tests even through that would be important to reduce the costs of understanding what happens. If we live in a world where we have a bunch of promising approaching for anti-aging drug development and our problem is that not enough capital goes towards persuing them, research that provides additional perspectives doesn't seem to be most important. If the model is that if SENS provides more approaches Greeves or Deming can fund more startups, the bottleneck isn't about moving exisiting approaches to trials.

2PeterMcCluskey5y

Baze has technology for cheaper and more convenient blood tests. So far they're only using it to sell vitamins. I presume regulatory obstacles are delaying more valuable uses.

1JackH5y

Just looked it up - looks promising. Thanks for sharing.

2JackH5y

Sorry, I don't quite follow - what's the point here? That funding SENS alone is unwise? If so, I don't think that's the major concern, as SENS has a tiny budget (~$5 million) and have a good track record funding some of the best work in the field. By 'approaches' I meant, 'therapeutic approaches', not 'perspectives on aging'. What I tried to emphasize in the OP is we have a good-enough model (or, 'perspective') on aging which is the hallmarks of aging, and that the limiting factor now is funding to (1) develop new approaches to therapeutically addressing these hallmarks and (2) translate these findings into humans through the financing of longevity biotech startups, though (1) is the more important than (2).

2ChristianKl5y

I have two motivations here: (1) Having that argument between tool-spending and more application focused spending. Arguing that clash in detail is good for giving people an overview over it. The OpenPhil report on Mechanism for Aging asks here "How likely is it that general-application tools and basic research areas that might not be thought of as part of “aging research” (analogous to epigenetics, stem cells, neuroscience, and drug delivery) will be bottlenecks to accomplishing the core objectives described above? " (2) On average I think that tool research is not emphasied enough in biomedicine. It frequently happens that better tools make important new research possible. Thomas Kuhn argued that focusing to much on application usually leads to an academic field being very unproductive. When doing academic research you never know beforehand what you will find. Sometimes reserarch can evolve into a tool direction instead of an application direction. If a person is too much committed to an application direction (towards anti-aging) they might not persue valuable research directions. Similar things go when seeking jobs. I would expect that average person who works at DeepMind on protein folding to have a larger impact on ending aging then the average person at a biotech companies which has fighting aging as it's mission statement. In the large scale of funding, SENS budget is at the moment a rounding error, so I don't think that the extend towards which it's currently funded is a problem. I think it would be reasonable for SENS to have 10X the money it has but I'm doubtful 100X would currently be justified.

3JackH5y

I gave a more thorough analysis of why OpenPhil missed the mark somewhat in their 'medium-depth' inquiry of anti-aging research in response to your comment lower in this thread, which is relevant to this point. I'll add a couple of points: I completely agree with you that technology from other areas (AI, platform technologies etc.) will benefit aging research. But that's not the point - 100,000 people per day are dying of aging and we have the tools to test a bunch of drugs, and a huge laundry list of possible drugs to test (AKG, Gemfibrozil, rapamycin, spermidine, etc.) but we don't have the funding to do it. So, donating to SENS is important to pick the lowest hanging fruit i.e. testing drugs we are already pretty sure do slow aging. To give an analogy - you could say that given advances in materials engineering would help us get to Mars, but you also need Elon Musk (or equivalent) to put the pieces together and do the thing. Anti-aging is the same - although today's platform technologies are not perfect (just like today's material science is not perfect) there are so many experiments we can perform now that would save potentially millions of lives, and should be prioritized. Remember that anti-aging almost certainly will happen eventually if society doesn't collapse, and what the field is fighting for is for this to happen sooner rather than later, so that many more people alive today will benefit. The above is actually an additional criticism I had of the OpenPhil. It's not that Aubrey de Grey and and others in the field don't think advances in other areas will help (AI, etc.), it's that there are so many feasible projects that should be funded that could potentially have a huge impact on populations today, that are not being funded. The neglectedness of the field is the primary reason SENS needs more funding, - think of SENS as funding a locus of research that has among the highest probability of progressing the field in the near future, given this resear

2ChristianKl5y

I think it's worth putting such a critique into it's own top-level post sooner or later. It more likely engage OpenPhil. And we have a very profit oriented industry that makes money with making good calls on judging which possible drugs as worth testing. It's relatively easy to make an argument that certain basic research that's valuable but not directly profitable are underfunded. The term valley of death is about drugs where we are not pretty sure that they have a clinically useful effect. There's no reason to believe that material science progresses in a way that makes building starship 10X cheaper within a decade unless people are working on the technology. On the hand there are plenty of experiments that are run in antiaging that plausibly could get 10X cheaper through tooling improvements.

2JackH5y

Will do. If it works (slows aging) then it will be profitable. If by 'tooling improvements' you mean, biomarkers of aging then I completely agree with you. This is also research within the aging field that requires more funding. Besides that, I'm not sure what kind of tools you think we need. The bottom line is that we have a bunch of drugs, and we need a measuring stick (accurate biological age test) to tell us whether the drugs slow aging or not. What other platform technologies would be needed to expedite this process?

[-]freyley5y20

I'm in support of anti-aging research, and think we should fund it more highly, specifically because the long-term benefits are so high once we get it right. Does anyone have any comments on whether SENS is the best place to put money if you're interested in donating to anti-aging?

As a side note, my experience working with complex codebases has led me to disbelieve your optimism for how quickly we can find reliable ways to get more than a decade of increased healthspan. The human body is vastly, vastly, vastly more complex than nearly any codebase hu... (read more)

5Victorel Petrovich5y

Yes, organisms (even worms) are way more complex than any codebase so far, and researchers don't fully understand them and yet - as you can see from this and other reviews - very significant lifespan (and healthspan) increases have been achieved. Even in mice and rats, which, aside from an inferior brain, are about as complex as humans. To me, this indicates that the aging process is quite malleable, with many ways to tweak it, which researchers are finding through theories, educated guesses and trial and error.

3JackH5y

(1) Charity recommendations I would recommend donating to SENS Research Foundation or Lifespan.io. SENS has funded a lot of really great research in the field, which you can view here. Lifespan is involved in advocacy, and have been successful in hosting conferences and providing a platform for information sharing in the field. They have also crowdfunded some research. Both the research and advocacy components are crucial for helping to expand the longevity field. (2) Complexity of aging Yes, the causes of aging are complicated - that is, how the damage accumulates - is complicated. But treating aging doesn't actually require understanding how the damage accrues, using the SENS (strategies for engineering negligible senescence) approach. It only requires how to ameliorate the various types of damage (hallmarks of aging). Bear in mind that overwhelming evidence in the past 20 years has suggested that all aging-related processes are, looking upstream, a result of the hallmarks of aging and that there is no other cellular phenomenon besides these 7-10 processes (depending on how they are classified) responsible for the aging process that cannot be reduced to them. In the past 20 years, no new hallmarks have been discovered and researchers are fairly confident that these are the only hallmarks there are to discover. Here's Aubrey de Grey's explanation of the SENS approach: "The basic point we're making there is to contrast the regenerative approach with the more traditional idea of trying to make metabolism create molecular and cellular damage more slowly. In order to do the latter, we would need to understand our biology massively better than we do at present, so as to avoid creating unforeseen side-effects. By contrast, with the regenerative approach we don't need to know much about how damage comes about: it's enough just to characterize the damage itself, so as to figure out ways to repair it. We're effectively sidestepping our ignorance of metaboli

2ChristianKl5y

Is there any polling about how many of the anti-aging researchers believe this thesis?

4JackH5y

To the best of my knowledge, there has not been polling of this question to anti-aging researchers (geroscientists) specifically. However, if you watch lectures by anti-aging researchers, and the major conferences such as ARDD, EARD, CSHL Mechanisms of Aging and so on, most of them seem to use this paradigm when discussing aging and many even have a slide on the hallmarks of aging. All of the big names such as David Sinclair, Brian Kennedy, Lynne Cox, Judith Campisi, Alex Zhavarankov, and many others all mention the hallmarks of aging. If you want further evidence, consider that the original paper, The Hallmarks of Aging (2013) published in the journal Cell is the most highly cited academic paper in the entire field - with over 6800+ citations. Although it was Aubrey de Grey who first conceived of the Hallmarks (which he called the '7 deadly SENS' and categorised them slightly differently in his 2007 book, Ending Aging) it has now become the framework used by researchers in the field, and even included in academic courses - such as the lectures I was invited to give to clinical neuroscience students here at Oxford University about aging and neurodegeneration. So it's fair to say that it is now the consensus that the hallmarks of aging is the predominant view of the field, even though this was not the case 10-15 years ago when other theories of aging such as the free radical theory of aging held more weight.

4ChristianKl5y

If you are in a position to be invited to such talks, it might be worthwhile to put information about your identity into your post. Maybe as part of a epistemic status tag on the top. The thing that's very unclear to me is why SENS has so little funding if that's framework is now consensus. It seems like while the metformin trial study seems like good value for money in contrast to typical NIH funding, funding it with a decade worth of SENS funds wouldn't be good value for money if SENS works. Why doesn't SENS succeed at having a 8 or 9 figure budget? Which arguments are keeping the billionaire money from funding it stronger while the metformin trial study did get it's money?

5Victorel Petrovich5y

I guess one reason is that billionaires don't have time to do their research in detail, to see for themselves whether de Grey and Sens are worthy, but rely on reputation and opinions of popular names in the field. And the reputation of SENS seems to have suffered a bit initially, when many scientists found their proposals for rejuvenation too bold or futuristic https://en.wikipedia.org/wiki/Aubrey_de_Grey#Criticism

3JackH5y

SENS Research Foundation aren't the only source of funding for research into the hallmarks of aging. The research into the hallmarks of aging labs at NUS, the Buck Institute, Oxford, Harvard and many other institutions is largely funded through the traditional route of national medical research councils. SENS Research Foundation funds some of the research, but by no means most of it. That said, they have a good track record of selecting some of the most important projects to fund despite a small budget of $5-10 million. For a point of comparison, the National Institute of Aging which as a $3 billion budget allocates around $100 million to geroscience.

1emanuele ascani5y

Because they choose the most neglected (long-term/difficult/high-risk high-reward) projects within the Hallmark framework (I talked extensively about this in my posts if you want to take a peek).

3ChristianKl5y

Why wouldn't billionaires (outside of Thiel and Greeves) that donate money for improving health outcomes want to fund long-term/difficult/high-risk high-reward projects? Do you know whether SENS request a grant from OpenPhil?

5JackH5y

Yes, and there are some signs that more billionaires (at least, the progressive-minded ones) are taking this seriously. For example, Elon Musk in an interview 3 weeks ago (timestamp: 24:03) mentioned the feasibility of 'stop[ping] aging' when asked about the biggest threats to the future of humanity, for the first time on the public record. Two scientific advisors from OpenPhil conducted a 'medium' depth investigation into anti-aging in 2017 and seemed to understand the problem, though were less optimistic about anti-aging timelines, and funding this research area. They made the following forecast: However, I would strongly disagree with this timeline, based on my knowledge of the field, today. I would go so far as to say that some combination of therapies available today - including metformin, senolytics, blood plasma exchange and epigenetic reprogramming - could already extend lifespan 25 years (compared to not taking the therapies) if personalised and multi-omics-biomarker-optimised. It's just that we need more research to know how, when, where and how much of these therapies are required for each individual. With another 46 years of research in a field that is already expanding, I have no doubt that 25-year lifespan extension will be available by 2067. They also summarised what a few of the anti-aging approaches (senolytics, stem cell therapies) but neglected many of the most promising approaches such as plasma exchange, partial epigenetic reprogramming, and mTOR inhibition. They also made a big mistake, in my opinion, by overevaluating the amount of funding that geroscience (i.e. research that is relevant to the development of anti-aging therapies) receives: It is clear to almost everyone working in the field that the amount of funding going towards geroscience - i.e. targeting aging therapeutically - is drastically lower than that of age-related diseases - which employ completely different research methods and experimental protocols (i.e. do not perform

3ChristianKl5y

Youtube allows you to link to specific timestamps when you click on the share button. I think there are two separate issues. One is about aging being taking seriously and the other is about SENS being taken seriously. I think you have the wrong link. In any case Aubrey de Grey basically here that hiring credentialed people is not enough to get results but that if he would organize the research it would produce better results. While that might be true it's hard to assess. That sounds like the people in the 1970s that they thought they could cure cancer by the end of the decade if they declare war on it.

1JackH5y

Thanks for the tip. Sorry, here is the link. It's not that hard to assess, given he has many informal chats with people affiliated with Calico. His point is that Calico has a huge budget but terrible internal structure that has essentially created an internal valley of death - many good aging researchers on good salaries, and many good pharma guys, but no-one who is actually developing and translating the technologies to solve aging (i.e. by repairing the hallmarks of aging). It's not an apt comparison for at two reasons: * Scientists were nowhere near understanding cancer in mice let alone curing it in 1970. By contrast, with anti-aging technologies such as senolytics we can already delay cancer (which kills 80% of mice typically) and extend healthy lifespan 30%. * Solving cancer is a potentially harder than slowing aging, since it involves intervening in the process further downstream i.e. when more damage has accumulated, rather than nipping it in the bud.

1emanuele ascani5y

I dont't know actually (for both questions). And I'm not sure how many billionaires like this there are.

3Florin5y

SENS and Hallmarks shouldn't be mixed as was done here and in the OP; although both sometimes overlap, they're separate and distinct. Aubrey de Grey was the first to categorize aging damage and strategies to repair that damage (SENS) back in 2002 and published Ending Aging in 2007 to further popularize it. But he didn't publish Hallmarks, and Hallmarks doesn't always overlap with SENS (e.g., no cure for cancer, ignores crosslinks). Hallmarks also advocates lots of messing-with-metabolism (gerontology rather than the engineering/maintenance/damage repair approach), which is a big no-no from the SENS perspective. And while Hallmarks is popular in academia, SENS is not, unfortunately. It all boils down to this: the SENS approach has a decent chance of reaching LEV in the not-too-distant future, whereas Hallmarks doesn't and never claimed to.

[-]ViktoriaMalyasova3y10

Hi! The link under the "Processes of Cellular reprogramming to pluripotency and rejuvenation" diagram is broken.

[-]YimbyGeorge4y10

I apologize for tldr. I think the most important thing is to prevent death of cells from low oxygen. If you solve he problem of nervous tissue dying from lack of oxygen, then you solve all coom problems like drowning, heart attacks, etc. Anything that cuts off oxygen will not kill you and. You will be invincible like a cockroach.

[-]Astynax4y10

For me, the case for doing this has not sufficiently been made. I read two sets of arguments for it. On this page, essentially, "aging is the leading cause of death," which is funny -- like engagement is the leading cause of marriage -- but more seriously: to attempt to abolish aging is largely about fighting death. Pointing out aging kills doesn't take us anywhere until we've shown death needs to go.

On the linked page about "pro-aging trance," it was that if I'm still asking that question, I must be in a trance, and that's not exactly sound.

I don't have c... (read more)

[-]Florin5y10

Partial reprogramming in mice has shown promising results in alleviating age-related symptoms without increasing the risk of cancer.

Actually, it's not really known whether or not partial reprogramming increases the risk of cancer.

[-]icemtel5y10

Is there any way for a small private investor to invest in this? By amount of risk, this is probably more of a charity than an investment, but with a small chance of hitting a jackpot.

Maybe some fund which invests into longevity projects? I could not find individual companies, which would be publicly traded.

2JackH5y

Hi icemtel, There are a number of publicly-traded longevity biotechnology companies. You could invest in Unity Biotechnology (NASDAQ:UBX) or Proteostasis Therapeutics (NASDAQ:PTI), for example. I also recommend the Longevity Market Cap newsletter. For larger investments, you could also look into longevity biotech VC's such as Apollo Health Ventures. Here are some links that may be useful: https://investoraccess.masterinvestor.co.uk/events/investing-in-the-age-of-longevity/ https://transhumanplus.com/investments-on-antiaging/ https://investingnews.com/daily/life-science-investing/longevity-investing/longevity-research-companies/ https://www.nanalyze.com/2019/08/top-10-companies-longevity/

1icemtel5y

Thank you for your time! I will take a look at these companies

[-]Victorel Petrovich5y10

On "Call to Action" :
Besides sharing, learning and donation, why don't you encourage research-minded people to actually participate in / join the research?

First, students or young researchers in position to choose or change their research direction.

Second, others: since the audience that will fully read such an article is likely to have useful research skills (biology, science, computer science etc ). Some may be willing to volunteer with their skills and join some project.

3JackH5y

Thanks for the tip - just added 'become a researcher' and 'work for a longevity biotech company' as additional ways to help the field.

1Victorel Petrovich5y

Thanks, the way you have included links to possible laboratories and companies is great!

[-]Victorel Petrovich5y10

Thank you for the great article!
One possible minor correction: turtles do senesce https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988574/

2JackH5y

You're welcome! I mentioned 'tortoises' rather than 'turtles' in the OP and was referring to species such as the Aldabra giant tortoise (Aldabrachelys gigantea). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743229/

1Victorel Petrovich5y

Thanks for correcting me, I didn't know turtles and tortoises are different! Another example, at least as good, of negligibly senescent tortoise, is Gopherus agassizii https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157354/

[-]AABoyles5y10

Without aging, COVID-19 would not be a global pandemic, since the death rate in individuals below 30 years old is extremely low.

A pandemic is an epidemic that occurs across multiple continents. Note that we can accordingly envision a pandemic with a death rate of zero, but a pandemic none-the-less. Accordingly, I think you've somewhat overstated the punchline about aging and COVID-19, though I agree with the broader point that if aging were effectively halted at 30, the death rates would be much, much lower.

4JackH5y

That's a reasonable challenge. However, the definition you cited (from Wikipedia) is the classical definition of a pandemic, and according to the WHO, does not take into account disease severity and transmissability, and would imply relatively harmless influenza outbreaks would also classified as pandemics - which is somewhat controversial in terms of definition. So depending on how you define a 'pandemic' (i.e. with or without disease severity and transmissibility taken into consideration) my original claim may be true.

1AABoyles5y

Fair point. It does seems like "pandemic" is a more useful category if it doesn't include a whole bunch of "things that happened but didn't kill a lot of people."

[-]AcurB5y10

"Recently, a group of Russian biohackers recently performed..."

Just reporting a little mistake here.

Good overview.

1JackH5y

Thank-you, fixed.

[-]jmh5y10

Regarding parabiosis, are you familiar with the Conboy's research on diluted blood plasma? I know they are trying to get a trial going -- but suspect the effort has been a bit delayed due on the main event for 2020.

2JackH5y

[-]NunoSempere5y10

The evidence is promising that in the next 5-10 years, we will start seeing robust evidence that aging can be therapeutically slowed or reversed in humans

Are you willing to bet on this? If so, how much?

5JackH5y

Definitely. There are over 50 therapies in clinical trials for aging today, addressing various components of cellular aging (i.e. all 9 hallmarks), and many have shown life extension effects in mice, and amelioration of the decline associated with age-related conditions in humans. I'm convinced some of these therapies, when administered from mid-life onwards, would extend human lifespan by 5 years or more. Especially if their delivery is personalised and biomarker-optimised. I expect some combination of these therapies, in tandem, to extend healthy human lifespan by 10 years or more. The challenge lies in proving this within the next 10 years, since it would take up to 50 years to run a full-length human lifespan study. So it comes down to how we define robust evidence that aging can be slowed therapeutically. For this, we need accurate biomarkers of aging, and unfortunately, we don't have the best aging biomarkers yet. On the other hand, one could argue we already have robust evidence that aging can be slowed from thymic rejuvenation (using GH+DHEA+Metformin) demonstrated in 2019 to reverse biological age by 2.5 years with 1 year of treatment. However, the extent to which this can be considered robust evidence that aging can be slowed depends on who you are talking to in the field, and their familiarity with aging clocks. If we are using epigenetic aging as the measurement, I'd bet all the money in my bank that at least one additional pharmacological compound will be shown to slow or reverse epigenetic aging in the next 10 years. That said, this measurement is likely to become redundant very soon, due to the development of multi-omics biomarkers of aging that will be more accurate in measuring aging. So overall, I'm very confident that some of the 50 compounds being trialed today, and certainly some of those that will be discovered in the next 10 years, will slow aging - which is a less controversial claim than many people realize since some of these thera

8ChristianKl5y

It might be worthwhile to formulate some of those predictions into Metaculus questions.

1JackH5y

It's a good idea. There is already one on essentially this topic: Will there be a culturally significant development in aging research by 2030? The median is 65% so it seems most people (at least, out of those who have responded here) seem to agree with my 10-year timeline for important discoveries. And this is another one anti-aging-related: Will a senolytic therapy be approved for commercial sale by the United States Food and Drug Administration before January 1 2030? The median is 58% for this one. I haven't used Metaculus before and I don't know what value I could bring by signing up for Metaculus and adding new questions. I intuit that my time would be better spent progressing the research forward so the optimistic predictions actually occur, rather than endless forecasting. That said, I don't know much about how Metaculus works. If you think it's a good platform for outreach and educating people about the field then I would consider it. Or, if you think there are certain kinds of questions I should ask (e.g. regarding the success of individual anti-aging approaches, maybe?). Let me know.

3ChristianKl5y

When it comes to good long-term strategy and investment of resources understanding how the future likely looks like can be helpful. The act of writing a good Metaculus question is about operationalizing thinking about the future. A question on the likelihood that research that's spun out of SENS leads to an FDA approved drug might be useful for outreach. Both getting people to seriously think about the likelihood is useful and also to be able to use it when talking about the value of donating to SENS to rationalists. For people outside the field it's hard to evaluate the value of SENS by reading papers on their website. On the other hand likelihood to lead to a FDA approved drug is a metric that's a lot easier to think about. Maybe you also have a better idea then likelihood of a FDA approved drug for your vision of the effect that SENS will have. It seems to me like your thoughts about the importance of biomarkers of aging could also form the basis for questions. Thinking about good questions is about thinking what kind of events will be important in the next 20 years and building clarity about that is useful.

1JackH5y

That seems like it could be a good idea. A few more questions though: How would writing the question help to convince people? Would it not only be convincing in 5-10 years' time if some of the predictions turn out to be accurate? Or, do you think if consensus on a Metaculus question that prediction X will occur is in and of itself convincing for rationalists? I'm still a little uncertain about the practical benefit of writing questions, in helping to advance the technologies.

1Neel Nanda5y

I would personally find a consensus on Metaculus pretty convincing (at least, conditional on there being a significant amount of predictions for the question). I find it hard to gauge other people's expertise and how much to defer to them, especially when I just see their point of view. Aggregating many people's predictions is much more persuasive to me, and many of the top Metaculus predictors seem to have good epistemics.

5JackH5y

Great - have you seen the existing Metaculus questions on anti-aging by Matthew Barnett and others?

0Neel Nanda5y

Ooh, no. That's super interesting, thanks!

1NunoSempere5y

Thoughtful answer, thanks

[-]bardstale5y00

A very long article about anti-aging and not a single mention of the effect of insulin and carbohydrates on ageing. No mention of the use of a ketogenic diet as an anti-ageing strategy.

At least you mentioned Metformin...

8JackH5y

Hi bardstale, 'Deregulated nutrient sensing' is one of the 9 hallmarks of aging covered in the article, and includes insulin signaling (IGF-1, etc) - that is, insulin signaling pathways. Dietary protocols such as the fasting-mimicking diet (FMD) and ketogenic diets attenuate IGF-1 which is potentially beneficial for longevity. However, lifestyle protocols were not the focus of this article, since ultimately, lifestyle interventions alone are not likely sufficient to extend maximal lifespan beyond 125 years. Another way to phrase this, is that these diets are 'anti-aging' insofar as they slow the rate of aging, but not reverse it to a level that could potentially be achieved with therapies. The goal of anti-aging research is to provide new therapies that can allow us to live much longer than is available with the best approaches today (diet/exercise/meditation/low stress etc.).

2icemtel5y

Why don't you provide some references for other readers?

[-]Pedro Sachs5y00

It seems to me that unlike say, GAI research very little attention has been paid to the consequences of such work. I do not see how this would not result in a tiered society where at least at first those with access to longevity will be the wealthy and resourceful and thus able to tyrannise those that dont.

There are then of course a myriad of psychological/existential implications which someone like Scott Alexander would have a field day with. How can we give our time meaning if we have an unlimited amount of it? What about personal relationships? Or voca... (read more)

4JackH5y

This is true, and indeed there has been very little social sciences research on longevity that I am aware of, besides public attitudes towards longevity. Given the highly probable rise of anti-aging technologies in the near future, social science should focus its attention on modeling the impacts of longevity on social systems, political systems, and so on. Distributional justice is a very common objection to life extension that has been addressed at length by many in the field. This article and this site do a good job at laying out the arguments, and David Wood who I recently interviewed discusses this point, as he does in great depth in his book, The Abolition of Aging. I'll summarise some of the responses to distributional justice (i.e. 'only for the rich') arguments below: * Anti-aging therapies are in principle no different from existing medical treatments such as anti-viral or anti-cancer therapies. For example, there is little philosophically difference between a cancer therapy (e.g. molecules that kill cancer cells) to extend healthy lifespan and a senolytic drug (e.g. molecules that kill senescent cells) to extend healthy lifespan. In the same way that few would object to the development of better cancer therapies today (e.g. CAR T-cell therapies) that only the rich can afford (and are not, for example, currently available to people in Africa), few should object to anti-aging drugs that extend healthy lifespan, even if only the rich can initially afford them too. Basically, many lifesaving medical interventions are initially expensive, and therefore only available to the rich, but this isn't a reason to inhibit research. An additional point: if you support current medical research - which functions essentially to extend healthy lifespan, you should also support anti-aging, which also aims to extend healthy lifespan, though through prevention rather than cures. The only difference between the two is the approach, and the likely effectiveness - anti-ag

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