All of JackH's Comments + Replies

Thanks for sharing! Can I please request the following:

'An outback Australian landscape with T-rex dinosaurs being chased by ducklings'

'The Buddha attaining enlightenment with galaxies entering his mind'

'An AI using a laptop computer to watch YouTube'

'The Tesseract from the movie Interstellar, with inverted colours'

'The aftermath of Global nuclear war'

I'm so curious! Thanks a lot!

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-r... (read more)

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 rem... (read more)

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

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

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 thes... (read more)

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/... (read more)

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/m... (read more)

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). 

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

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

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 (me... (read more)

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

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/

I think it's worth putting such a critique into it's own top-level post sooner or later. It more likely engage OpenPhil.

Will do. 

It's relatively easy to make an argument that certain basic research that's valuable but not directly profitable are underfunded.

If it works (slows aging) then it will be profitable.

On the hand there are plenty of experiments that are run in antiaging that plausibly could get 10X cheaper through tooling improvements. 

If by 'tooling improvements' you mean, biomarkers of aging then I completely agree with you. This is als... (read more)

Youtube allows you to link to specific timestamps when you click on the share button. 

Thanks for the tip. 

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.

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 ... (read more)

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, rap... (read more)

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 pos... (read more)

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 resear... (read more)

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.

It seems to me that unlike say, GAI research very little attention has been paid to the consequences of such work.

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. 

I do not see how this would not result in a tiered society where at least at first

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. 

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. 

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.  

Thank-you, fixed. 

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.).

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. 

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
• Na

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.

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 ... (read more)

Yes, the Conboy lab are doing some of the best research in the field. The Brunet 2019 review I linked in the OP cites work from Conboy's lab on plasma dilution / parabiosis. I know that the company affiliated with Wyss-Coray's company Alkahest have plasma trials for Alzheimer's. 

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

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. 

Sorr... (read more)

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 l... (read more)

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. 

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?

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.... (read more)

I encourage you to read the full article, not just the first paragraph. Specifically:

A new breed of biotechnology firms, unencumbered by the accumulated practices and systems of large traditional ones, are pioneering impressive new digital capabilities. In the process, they are nudging the industry as a whole in this direction. This could significantly boost R&D productivity, benefiting both pharmaceutical companies and the patients they serve.

In recent years, a number of biotechnology companies have applied genetic-information-driven technologies to f

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

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:

• Is Human Life Extension Possible? - LongevityAdvice.com
• Longevity FAQ - Laura Deming (who is a longevity biotech VC)
• Lifespan by David Sinclair
• Endi

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.

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 eith

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!

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. 

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. 

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. 

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 s... (read more)

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. 

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.  

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:
 

The first application of tissue engineering is preclinical drug testing. Drug development starts with preclinical animal testing, but the vast majority of drugs that work in animals do not work in people. Estimates vary, but about 97% of preclinical leads that enter clinical trials do not exit them. Human organoids are a potential alternative that could allow at least s

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.&nb... (read more)

Fixed, thanks!