So much one could critique in this article, but one simple question: should we also stop doing cancer/CVD/dementia research? These are also intended to extend the period of healthy lifespan. The only difference with anti-aging is that it’s targeting the root cause (i.e. biological hallmarks of aging) rather than the symptoms of aging i.e. diseases of aging. And if you believe we should pursue only the less effective means of extending healthy lifespan, you would need to find some compelling reason to justify spending $billions on extending lifespan by a few months, rather than potentially several years/decades.
JackH
Karma: 562
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/
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.
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 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.).
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/
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/
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 (megadose, 5 g / day +, spread throughout the day)
Piracetam + Choline
Uridine
Acetylcarnitine + N-acetyl cysteine
Glycine
Supergreen/superfruit blend*: “Blender Culture” .
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 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?
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 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).
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.
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.
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 research is working directly on the problem.
So yes, I agree that increasing SENS’ budget by 10-20X would probably be sufficient and that once this point has been reached, the marginal ROI would fall. However, it’s also worth considering that the type of research funded by SENS could also drastically change as the field grows, which may still make SENS donations above the 20X point remain cost-effective. Either way, SENS needs more money today.
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 passions and so on) biological aging—that is, our slow and fatal physiological decline by the 9 hallmarks of aging that are slowly killing us, that currently accompanies chronological aging—doesn’t. If you think people get happier as they get more frail, weak, lose their sight, hearing, and have higher chances of cancer, heart disease, Alzheimer’s and type 2 diabetes just take a closer look at depression statistics—the highest rates of depression are among the elderly, who account for the most DALYs of any age demographic, from depression.
Honestly, ask yourself—do you think there is any meaning associated with neurodegeneration, and Alzheimer’s disease? Because as a neuroscientist I can tell you that it is impossible to age without neurodegeneration, which leads to extremely high rates of Alzheimer’s disease in the elderly. Neurodegeneration involves losing one’s memories, cognition and other mental faculties, which also predisposes to depression, so it’s unclear how this process would be valuable for improving wellbeing, as you suggest.
The attempt to ascribe ‘meaning’ to the suffering that accompanies biological age-related decline and the diseases it is associated with (cancer, heart disease, type 2 diabetes etc.) is just a manifestation of the naturalistic fallacy coupled with lazy conservatism inherent in human nature.
The reality is: biological aging f*cking sucks, and no person who is experiencing the decline associated with aging (frailty, heart problems, signs of cancer etc.) would give up the opportunity to take therapy to bring them to a more youthful state of being biologically 20-30 years old with complete physical and cognitive function, given the opportunity. If you have compelling evidence on the contrary, please provide it.
For more about deathism, the pro-aging trance and ‘death brings meaning to life’ arguments, read articles, here, here and here. Also consider reading Aubrey de Grey’s book, Ending Aging David Sinclair’s book, Lifespanand David Wood’s book, The Abolition of Aging.
(2) Distributional justice (i.e. ‘only for the rich’)
Will the “anti-aging cure” (considering aging as a disease still rings a bit weird to me) be available to all strata of society? Or will it only enlarge the cleft between haves and have nots?
I covered this in another comment in this thread, but will copy and paste the response for your convenience:
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-aging is likely to be more effective at accomplishing the goal. Hence, we should be more enthusiastic about this approach, if anything.
Therapies are unlikely to stay expensive for long. When patents expire after 10-20 years, drugs usually become ridiculously cheap, and so any distributional inequality is unlikely to last long. Metformin, a life-saving diabetes drug (that is also being studied for its anti-aging properties) is a good example—it was initially expensive but the price has now plummeted to 31 cents per tablet in 2013. There are numerous economic forces that will drive low prices—governments are incentivised to subsidise these therapies, to populations healthy and stave off the diseases of old age that cost healthcare systems trillions of dollars worldwide annually (e.g. dementia alone costs over $1 trillion), which is otherwise set to grow due to an aging population. Insurance companies will similarly be incentivized to subside these therapies, to keep their clients healthier and able to avoid the chronic diseases of old age for longer. A good analogy is car sales—cars used to be too expensive for most people but are now ubiquitous and largely affordable. Since the market size for anti-aging therapies (i.e. all humans on Earth) is huge, as it is for cars, we would expect the huge demand to result in lower prices. Food technology is another, more recent example. In 2013 the first lab-grown burger was $325,000, and two years later the cost fell to $12.
Not developing anti-aging technology doesn’t help the poor. Anti-aging technologies only available for the rich would not help the poor, but not having these technologies available to the rich—that is, allowing the rich to age and die like the rest of us—also wouldn’t help the poor. What matters is not only that the gap between rich and poor is closed, but also how it is closed. For example, those in Western countries could give up all their comforts and wealth to be economically equal to the lowest African countries. But this is not the goal—the goal is to bring the African countries up in wealth, not bring economically prosperous nations down. The same applies to anti-aging: the goal is to bring everyone’s healthspans up (even if it means there will exist some inequality, initially), not keep everyone’s healthspans down for the sake of equality.
(3) Overpopulation and resource constraints
The initial question is purely pragmatic: more people on Earth living longer lives would mean more energy expenditure, more space needed to accommodate them. Even if this could be technologically solved with higher efficiencies (which themselves would not be offset by behavior adaptation), what will it do to the fabric of society?
Demographics The Earth’s population today is not expanding in an uncontrollable, exponential way and in fact in many parts of the world population is either now or soon will be declining (e.g. European countries, Japan, China etc.). The only regions of population growth are south-east Asia and Africa, both of are predicted to at around 11 billion in 2100 in line with the demographic transition model and then fall. In many parts of the world, underpopulation is likely to be a bigger problem than overpopulation in the near future due to dangerously low birth rates.
Aging population A much bigger problem than overpopulation is the ‘aging population’ and carrying capacity (i.e. the proportion of individuals over 65+ and frail etc. due to age-related decline) which is increasing globally and will immensely burden the healthcare system, and the younger workforce, in the absence of anti-aging technologies. However, anti-aging technologies allow those in their 60s and beyond to remain in a healthy, functional state and able to work and remain free of chronic diseases for much longer.
Neo-Malthusian collapse: The notion of overpopulation is common misconception that is completely unsubstantiated by empirical literature. Neo-Malthusian concerns have been touted since the 18th century but have not held up since as populations expand, so too does the technology to support larger populations. The whole notion of ‘carrying capacity’ assumed there was no possible way to (for instance) increase crop yields, fortify foods, significantly increase population density via taller buildings and so on.
Won’t a larger population exacerbate climate change? Climate change is a huge problem and while population size is a multiplicative factor in environmental impact, developing technology to decrease carbon intensity and increase and recycling effectiveness, as described by MIT economist Andrew McAffee in his book, More from Less, is feasible and the rational solution. As David Wood says in my recent interview with him: ‘if we are serious about solving aging, we should not fetishize population size (as a factor), we should be working elsewhere’. Interestingly, many of the technologies that will make rejuvenation biotechnology possible can also assist with transforming agriculture to claim back land that is currently being used inefficiently, such as synthetic biology (lab grown meat) and nanotechnology (repair and recycling). Additionally, geoengineering solutions (green energy—solar/wind), space tech, and policy changes may help to reduce emissions. So although the world is already transitioning to renewables, (for example, the UK recently passed the benchmark of 50% renewables) and the rate is not necessarily fast enough, restricting population size by allowing the widespread suffering and death from aging is not the most ethical nor effective way to manage climate impact. In the same way that allowing COVID-19 to kill millions of people is not an ethical solution to climate change (which, by the way, is primarily an age-related disease that would benefit greatly from anti-aging, as I will discuss in a future post).
We won’t run out of space? In 2012, the team of the project “Per Square Mile” led by Tim de Chant produced an infographic to show how big a city would have to be to house the world’s 7 billion people. If populated as densely as New York, the entire world’s population could fit into an area the size of Texas. So there is more than enough space on Earth to accommodate a vastly greater population of many trillions.
Won’t we run out of food? If we compare the food supply in 1965 and in 2013, we can clearly see that overeating is more of a global issue than undernourishment, as in most countries, the calorie intake has increased significantly. If we compare the food supply in 1965 and in 2007, we can clearly see that overeating is more of a global issue than undernourishment, as in most countries, the calorie intake has grown significantly. This means that a population explosion during this time of over 4 billion people
has passed relatively unnoticed – all thanks to the “Green Revolution” (rapid development of new agriculture techniques, such as fertilizers, irrigation and selection). The concern that there will be a food shortage in the future neglects further technological advances such as aquaponics, hydroponics, aeroponics, vertical farming, 3D-printed housing, algae farms, and many other technologies that could provide enough food for all.Negligible senescence: Now, eventually if we completely abolish death (i.e. achieve ‘negligible senescence’), then yes population size will continue to grow, assuming populations continue to reproduce. But this population growth is 1) not as rapid as people imagine 2) not a concern that is unlikely to be solved by technological advances and 2) not a reason to deny those alive today access to life-saving anti-aging therapies.
For a more detailed response to this objection, I recommend this long-form article.
Final comment: Anti-aging is basically just today’s medicine, but better (and preventative)It’s worth noting that all of the above objections also apply to current medicine too (which similarly aims to extend healthy lifespan) albeit to a lesser degree due to the ineffectiveness of this approach. The philosophical difference is that anti-aging is potentially more effective at accomplishing medicine’s goal—to extend healthy lifespan—by targeting the root cause of the problem (hallmarks of aging) rather than allowing the damage of aging to accumulate and then only targeting the ‘symptoms’ (i.e. diseases of aging—cancer, heart disease etc.). It seems strange to me that you would support (I assume) the less effective approach to healthspan extension of today’s medicine, but not support the more effective approach of anti-aging. Ultimately, the two approaches service the same goal, but one intervenes earlier, when the damage has accrued but before symptoms emerge rather than when damage has accrued to an even greater level that causes symptoms to emerge. ‘Prevention is better than a cure’ as they say, and this certainly looks to be the case with anti-aging.
Note: if you found some of these arguments more/less compelling than others, please let me know as it will help to inform my second post :) thanks.
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:
Our program officer Nick Beckstead offers the following forecast to make the above more precise/accountable: By January 1, 2067, there will be no collection of medical interventions for adults that are healthy apart from normal aging, which, according to conventional wisdom in the medical community, have been shown to increase the average lifespan of such adults by at least 25 years (compared with not taking the interventions). (Subjective probability: ≥93%)
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:
The NIH reports spending $2.7 billion per year on aging research in 2015.16 In the 2015 budget request, $510 million per year is tagged as “neuroscience” and $177 million per year is tagged as “aging biology.”17 We have heard in various conversations that this research is mainly relevant to addressing particular symptoms associated with widely-recognized diseases (e.g., Alzheimer’s disease), rather than on understanding the basic mechanisms that cause aging. This is plausible to us, but we haven’t seen any convincing evidence for it and we do not take it for granted.
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 lifespan studies with geroprotective interventions prior to disease onset). A list of most of the researchers working in the field is here (last updated April 2020) though I don’t think OpenPhil cared to look deeply enough into the field to recognise the lack of researchers and funding for geoscience in particular.
There are other flaws in their analysis. For example, they mentioned the large funding that Google-backed Calico receives, here:
Some aging-focused companies working in this area that we became aware of in the course of this investigation include Calico ($500 million in disclosed investment and agreed upon potential for $1B more);24
However, as Aubrey de Grey explains in this interview, Calico—despite having a huge budget—have a poor organisational structure that has so far precluded any meaningful research advances in the field.
As Aubrey de Grey puts it in the interview (from ~1:14:00 onwards):
They [Calico] have created a vast valley of death internally....they’ve got this paradise of research where they’ve hired fanastically good researchers in large numbers paid large salaries to find stuff out; to increase our understanding of what aging is. And on the other end they’ve got these people who know all these people who know all about how to turn proof of concept into a product—and they’ve got zero in the middle. They’ve got nothing that turns knowledge into proof of concept.
So overall, I believe OpenPhil are inaccurate in their assessment of the geroscience field based on their ‘medium’ depth investigation into it. There are numerous other examples of statements in their write-up that demonstrate a poor or incomplete knowledge of the state of the field—both scientifically and economically. I can go into these if you like, and I’ll probably write up a post about this in the future.
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!