Extremely large payoff from life extension

We live in special period of time when radical life extension is not far. We just need to survive until the moment when all the necessary technologies will be created.

The positive scenario suggests it could happen by 2050 (plus or minus 20 years), when humanity will create an advanced and powerful AI, highly developed nanotechnologies and a cure for aging.

Many young people could reach the year 2050 without even doing anything special.  

But for many other people an opportunity to extend their life for just 10-20 years is the key to achieving radical life extension (at least for a thousand of years, perhaps even more), because they will be able to survive until the creation of strong life extension technologies.

That is why even a slight life extension today means a potentially eternal prize. This map of the currently available life extension methods could help in it. The map contains a description of the initial stage of plan A from the “Personal Immortality Roadmap” (where plan B is cryonics, plan C – digital immortality and plan D – quantum immortality).

Brain is most important for life extension

The main idea of this map is that all efforts towards life extension must start from our brain, and in fact, they must finish there too.

First of all, you must have the will to conquer aging and death, and do it using scientific methods.

This is probably the most difficult part of the life extension journey. The vast majority of people simply don't think about life extension, while those who do care about it (usually when it's too late) use weak and non-scientific ways and methods; they simply don't understand that the prize of this game is not ten of healthy latter years, but almost eternal life. 

Secondly, you need to develop or mobilize the qualities inside yourself which are necessary for simple, daily procedures, which can almost guarantee life extension by an average of 10-20 years. e.g. avoiding smoking and alcohol consumption, daily mobility, daily intake of medicines and dietary supplements.

Most people find it incredibly difficult to perform simple actions on a permanent basis, for example even taking one pill every day for a year would be too much for most people. Not to mention quitting smoking or regular health check-ups. 

A human who has the motivation to extend his life, a proper understanding of how to achieve it and the necessary skills to realize his plans, should be considered as almost a superman. 

On other hand, while all of our body systems are affected by aging, our brain damage during aging plays the biggest role in total productivity reduction. Even though our crystallized intelligence increases with age, our fluid intelligence, our memory, and the possibility of making radical changes and acquiring new skills all decrease significantly with aging.

And these abilities decrease at the very time when they are needed most – to fight the aging process! Young people usually don't care too much about the aging process, because it's beyond their planning horizon. These qualities are vital in order to build the motivation and skills required to maintain health. 

Thus, this leads to the idea of the map, which says that all main efforts to combat aging must be focused on brain aging. If you can keep your brain youthful, it will create and implement new skills to extend your life, helping you to find new information in a sea of new publications and technologies.

If Alzheimers is the first sign of aging to reach your body, you will have to crawl for a tablet of validol without even knowing that it is harmful. And even worse, you will crystallize some harmful beliefs. A person can think that he is a genius in some fields, receive approval from others, but continue his journey in the wrong direction – in the direction of death. (Of course early detection of cancer and a healthy heart are really important to extend your life, but it will be too difficult to deal with such problems if your brain is not working properly).

The second reason to invest in brain health and regeneration is a direct connection of its state with the state of many other systems in your body through nervous and hormonal connections. 

In order to preserve your brain health we have to use antidepressants, nootropics and substances which promote its regeneration.

The example of Rita Montalchni is incredibly interesting (https://en.wikipedia.org/wiki/Rita_Levi-Montalcini). She administered a nerve growth factor (NGF) as eye drops and lived for 101 years while her twin sister died when she was 91. (Bearing in mind the average life duration difference of twins is six years, we can conclude that she gained about four years.)

Thus, providing that we understand the priority of tasks, life extension now can be reached through three fine-spun blocks: a lifestyle, a medication and the prevention of aging itself.

Collective efforts in life extension

This map doesn't include one really important social aspect of aging prevention. If we could absorb all the money (through crowdfunding), which people use to buy supplements (around 300 billion per year), and use it to perform experiments in the field of life extension instead, we could invent new anti-aging medicine and other life extension tools. These methods and medicines could be used by those who initially donated money for such experiments; they could also benefit from sales of such products. Thus, such crowdfunding would include IPO too.

You won't find other social aspects in the map such as promotion of the idea of the fight against aging, political activism and art. All of these aspects are mentioned in the main Immortality Roadmap.

The map also doesn't include a temporal aspect. Our knowledge about the best methods of life extension changes almost daily. This map contains ideas which are valid in 2015, but it will require a significant update in just five years. If you aim to extend your life you must perform a constant analysis of scientific research in this area. Currently many new methods are appearing every day, e.g. ways of lengthening telomeres and gene therapy. Additionally, the older you are the riskier new methods you should try.

The map of ideas

In fact, the map contains a systemized analysis of ideas, which can lead to life extension, but not a bunch of well-proven tips. In an ideal situation such a map should contain links to research about all the listed items, as well as an evaluation of their real effects, so any help on improving the map will be welcomed.

This map (like all my other maps) is intended to help you navigate through the world of ideas. In this case it includes life extension ideas.

Moreover, one single idea may become a salvation for a person, e.g. eradicating a certain chronic disease. Of course, no single person can complete all of the ideas and suggestions in this map or indeed in any other list. I'm pretty sure that people will not be able to implement more than one advice per month – and I'm no exception.

My approach: I drink alcohol on really rare occasions, I don't smoke (but sometimes I use nicotine wrapping with nootropic objectives), I sleep a lot, I try to walk at least 4 km every day, I avoid risky activities and I always fasten my seatbelt.

I also invest a lot of effort in preventing my brain from aging and in combating depression. (I will provide you with a map about depression and nootropics later).

The pdf of the map is here, and jpg is below.

 

Previous posts with maps:

Simulation map

Digital Immortality Map

Doomsday Argument Map

AGI Safety Solutions Map

A map: AI failures modes and levels

A Roadmap: How to Survive the End of the Universe

A map: Typology of human extinction risks

Roadmap: Plan of Action to Prevent Human Extinction Risks

Immortality Roadmap

 

Future planned maps:

Brut force AIXI-style attack on Identity problem

Ways of mind-improvement

Fermi paradox map

Ways of depression prevention map

Quantum immortality map

Interpretations of quantum mechanics ma

Map of cognitive biases in global risks research

Map of double catastrophes scenarios in global risks

Probability of global catastrophe

Map of unknown unknowns as global risks

Map of reality theories, qualia and God

Map of death levels

Map of resurrections technologies

Map of aging theories

Flowchart «How to build a map»

Map of ideas about artificail explosions in space

Future as Markov chain

 

EDIT: due to temporary hosting error, check the map here: https://www.scribd.com/doc/286606304/Life-Extension-Map

Like most futurist-oriented people, I am fascinated by the idea of long-term life extension -- the notion that eventually people will have life expectancies of hundreds of years; thousands of years; or even more.  Although medicine has a ways to go in this area, one obvious approach is to take low tech steps to increase one's lifespan in hopes of living long enough to take advantage of possible future advances.  i.e., to roll with +1 dice.  Besides the obvious steps like wearing seat belts; getting regular exercise; eating a lot of fruits and vegetables, calorie restriction presents itself as an intriguing possible method of life extension.

In this essay, I will attempt to briefly define calorie restriction; assess how useful it might be; speculate about how it might be useful; and use the foregoing to justify my own personal approach to calorie restriction, which I will describe presently.  Of course I welcome comments and criticisms, especially since I am messing around with my own health.

I should note at the outset that I have no formal training or credentials in medicine nutrition or anything like that.  I'm just an attorney.

I should also add that my approach to calorie restriction is not a diet in the sense of being a weight loss strategy for people who cannot control their eating.  This is not a weight loss post!  I do not describe in this essay how I control my eating; control is assumed.

Last, my general approach is one of no regret.  i.e. My main priority in calorie-restricting myself is to avoid doing anything too radical in terms of loss of quality of life or risk to my health.

I. What is Calorie Restriction?

Wikipedia defines "calorie restriction" as follows:

Caloric restriction (CR), or calorie restriction, is a dietary regiment that is based on low calorie intake. "Low" can be defined relative to the subject's previous intake before intentionally restricting calories, or relative to an average person of similar body type.

So immediately we see a problem -- the concept of calorie restriction is ambiguous.  How am I supposed to evaluate and possibly implement calorie restriction in my life if I am not even clear on what it means?  This is not just a problem for laymen like me.  Imagine you are a researcher who is studying the effects of calorie restrictions in lab chimps.  How do you feed your control group of lab chimps?  Do you let them eat donuts and potato chips ad libitum?  Do you limit them to chimp chow?  Without a clear definition, this is a bit of a conundrum.

In fact, one individual has argued that the difference in treatment of control animals may be part of the reason why two studies on calorie restriction in monkeys had different results:

Further, the NIA study control monkeys were not truly fed ad libitum, unlike the WNPRC study. The regulated portioning of food for the NIA control monkeys may be a slight restriction and, thus, largely prevented obesity. Studies of 10% CR have been reported to increase lifespan in rats compared to ad libitum controls – even more than 25% and 40% CR²⁰. The NIA control monkeys may experience survival benefits from this slight restriction.

http://www.crsociety.org/science/nia_monkey_study

Another individual states as follows:

"Both the NIA and U Wisc studies need to be considered together for proper interpretation. It is clear that the U Wisc "controls" differ from the U Wisc CR group and BOTH NIA groups, and are probably most like the general populations of developed countries.

Because we at NIA wanted to avoid the criticism leveled at many rodent CR studies that controls are overweight and sedentary, we specifically designed our dietary conditions to supply an adequate, but not OVERadequate, caloric intake.

The bottom line is that, for most people (who are more like the U Wisc controls), CR may indeed provide both health (BOTH studies agree on THIS) and longevity benefits.....and of course, most important.....more "healthy years."

https://www.crsociety.org/index.php?/topic/2939-dr-george-roth-comments-on-calorie-restriction-and-nia-monkey-study/

For purposes of this essay, I will offer the following definitions:

1.  "Mild calorie restriction" = restricting calories sufficiently so that you avoid gaining large amounts of weight.

2.  "Moderate calorie restriction" = restricting calories sufficiently so that most of the time you are towards the bottom of your metabolic range.

3.  "Severe calorie restriction" = restricting calories sufficiently so that you end up spending your time significantly below typically fit people in terms of muscle mass and/or body fat.

The first and third definitions are pretty straightforward, although it's worth noting that a lot of people engage in mild calorie restriction unintentionally, just through the operation of their natural system which regulates their appetite/urge to eat/urge to stop eating (John Walker calls this the "food clock.")

The second definition requires a little explanation.   From simple observation, it appears that small changes in one's energy intake result in corresponding changes in one's metabolic rate.  So that if your weight is stable but you eat a little more or less than usual, you might notice that you are a little warmer or cooler than usual.  Evidently the body can and does make small adjustments to its metabolic rate in response to changes in food intake.  This is also consistent with dieters' reports that they feel cold when dieting.

II.     Does Calorie Restriction Work in Humans?

It seems quite likely that mild calorie restriction works in humans based on the observation that fat people have significantly greater mortality than thin people.

For example, as illustrated by the charts here:

http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMoa1000367&iid=f01&

Of course one cannot know this for sure since there is no ethical way to do a large controlled experiment, but still it's reasonable to infer cause and effect:  Common sense says that being fat puts a lot of abnormal extra strain on your system almost all the time.  In any event, there seems to be little downside to mild calorie restriction.

A more interesting question is whether moderate calorie restriction works in humans.  Common sense says that it ought to be beneficial based on the idea that slowing one's metabolism ought to slow the aging process, all things being equal.  One interesting area of research is studies which look at the effect of modest weight loss among obese people.  Is someone who goes from 250 pounds to 225 pounds and stays there more healthy than someone who goes from 210 pounds to 220 pounds and continues to gain weight?  If so, part of the difference might be that the second person is towards the top of his metabolic range while the first person is towards the middle or bottom.

The Calorie Restriction Society web site links to a couple presentations which argue that cancer is actually a metabolic disease related to having too much energy in play.  I'm a bit skeptical of this claim, but it does seem to me that you are inviting trouble by having extra energy floating around in your system.

As for severe calorie restriction, the jury is still out.  I don't put too much stock in the left side of the J-shaped curves comparing body weight to mortality.  Surely a lot of underweight people have serious latent health problems.  What's more interesting to me is that the curves flatten out between BMI of about 19 and 23.5.  This suggests to me that one can realize most of the benefits of reduced body mass by being normal weight and that after that, if there are any benefits, it's diminishing returns.

III.   My Approach to Calorie Restriction

I have decided to adopt an intermediate approach to calorie restriction, i.e. the aim is to stay thin and be towards the bottom of my metabolic range most of the time.  The health benefits to staying thin are pretty clear; there doesn't seem to be much downside; and frankly there are a lot of social benefits.  The benefits of staying towards the bottom of my metabolic range are more iffy, but again there doesn't seem to be much downside to it.  (Putting aside issues of health, the main downside is that it happens pretty frequently that I will have a meal and eat less food than I would have liked to eat.)

Severe calorie restriction seems too speculative to me to be worth the trouble.  Particularly given the social costs and the likely diminishing returns problem.  I like having a somewhat muscular appearance as opposed to a gaunt appearance.  Since my main priority is to avoid regrets, I am not willing to go this route without pretty solid evidence of benefit.

IIIa.  The Nuts and Bolts

What I do is this:  I have a basic daily diet which I believe is reasonably healthy and well-balanced.  Although it is somewhat flexible, it contains roughly the same proportions of macro-nutrients and is roughly the same amount of calories each day.  From careful observation, I have determined that my basic daily diet is about 500 to 600 calories short of my actual daily caloric needs.  i.e. if I stuck to my basic daily diet and ate nothing more, I would lose about a pound a week.  I add a small supplement of extra food to my basic daily diet if I work out at the gym in order to balance out the exercise.  (Interestingly, I once measured and it seems my basic daily diet, including the exercise supplement, is about 2800 calories.  This seems pretty high for a man who is thin, slightly below average height, and only slightly muscular in build.  I'm not sure what to make of it.)

I weigh myself every morning and calculate a 7-day moving average of my weight.  I then subtract this number from a pre-determined reference weight and multiply the result by 100.  This is the number of additional calories I consume that day in the form of reasonably healthy foods.  The idea is to eat close to the minimum to maintain weight, thus staying thin and towards the bottom of my metabolic range.

Now and then my weight spikes upward when I have an event which involves a lot of eating; after that it drifts back down again.  I've been calorie-restricted in this way for some time now.  I feel perfectly fine but after every meal I feel like I could easily eat more.  I pretty much never get heartburn anymore.  I usually wake up quite hungry.  These are about the only effects I have noticed.

IV.  Self-Criticisms of My Approach

In the interest of rationality, it probably makes sense to offer some self-criticism:

1. I found the above scientific references only after I had settled on my approach to calorie restriction.   So there is probably a certain backwardness about my reasoning.  My conclusion is based more on my own intuition, reasoning, observations and common sense than on scientific research.

2.  It never occurred to me to regularly measure my body temperature before and after starting this program.  Which is unfortunate because it may have given me some useful information about the effects of my diet on my metabolism.

3.  There's really no way to measure if any of this is having an effect on my rate of aging.  Without this sort of feedback, I'm pretty much shooting in the dark.

V.  Conclusion

So that's about the extent of my self-experiment.  It's a bit frightening that I'm putting my own health on the line in the face of so much uncertainty.  At same time, it seems like a reasonable, conservative approach which is unlikely to lead to regrets.  Of course there is an excellent chance I will never know how much of an impact my lifestyle had on my overall health.

Anyway, I welcome any intelligent thoughts, suggestions, constructive criticism, etc.

The paper is called DNA methylation age and human tissues and cell types and it's from Genome Biology. Here is a Nature article based on the paper.

I have submitted this to LW because of its relevance to the measurement of aging and, hence, to life extension. Here is a bit from the Nature piece:

"Ageing is a major health problem, and interestingly there are really no objective measures of aging, other than a verified birth date," says Darryl Shibata, a pathologist at the University of Southern California in Los Angeles. "Studies like this one provide important new efforts to increase the rigour of human aging studies."

Note: The discrepancy in spelling ("ageing" vs. "aging") is in the original.

I just read this article (which is well worth reading for anyone interested in cryonics).  One of the important things that the article points out is that, while it takes some time for the memory structures of the brain to degrade due to ischemia, one of the more rapid effects is blood clotting in the fine capillaries of the brain after fairly brief ischemia.  This reduces the flow of cryoprotectant, and causes large swathes of neural tissue to be frozen, instead of vitrified, which would be catastrophic for personal identity.  While this is not a problem for best-case 'standby' cryonics, it is a problem for those who cannot afford a standby team, or are simply hit by cars.

Being an engineer, my first thought is that this is ridiculous, and there has to be a better solution to the problem.  It may be possible to build a device, maybe the size of a shoe box, which can be deployed in the field by a minimally-trained amateur (like a defibrillator), and perfuses the brain with cold saline and anti-coagulants -- or even a synthetic oxygen carrier).  I'm picturing a cylinder of fluid, large needles with sterilizing caps for tapping the jugular and carotid arteries, and a gas cylinder to provide pressure.  You'd simply break a chemical cold pack, put a plastic neck brace in place and insert the needles, and press a button.

Such a device could even be useful to non-cryonicists, as a way to prevent ischemic injury in people found medically dead at the scene of an accident, during transport to the hospital.  

Does anyone with more of a medical background know if such a machine would be at all feasible?  I can't imagine it would be expensive to construct.      

Aubrey de Grey, Chief Science Officer of the SENS Foundation, has posted a video with answers to some of the questions posed at him in a recent Reddit AMA.

Link: http://www.youtube.com/watch?v=6eet44YacRg

Although there are no long-term scientific studies of calorie restriction in humans, there are religious groups, cults, and ascetics who voluntarily practice calorie restriction or intermittent fasting. Presumably there have been tens or hundreds of thousands of people who have practiced calorie restriction throughout most of their adult lives. There were/are probably also groups that involuntarily practice calorie restriction - servants, slaves, prisoners, or people who simply regularly don't have enough to eat.

 

If calorie restriction has a dramatic effect on life expectancy in humans, shouldn't we expect to observe extended life expectancy in at least some groups? Or would each of these groups likely have some mitigating circumstances that would shorten their lifespans, such as lack of medicine?

 

With an hour on Google, I found some references to Okinawa, to monks on Mount Athos, and to similar groups. In no case was there a reasonable claim of life expectancy over 90 (which would represent just a 10% improvement over life expectancy in Japan).

 

This paper reviews the evidence on calorie restriction in humans and other animals, including discussion of religious fasting, but there's no evidence there of fasting extending lifespan.

I found a few other sources where people asked this question (or made this point as an attack on CR), but I haven't yet found any good answers on the subject, and didn't find any discussion on LessWrong yet.

Briefly Start the week is a popular BBC radio 4 program discussing scientific and cultural events in the UK. This episode covers a lot of issues relevant to Less Wrong.

In their own words: 

"Andrew Marr explores the limits of science and art in this week's Start the Week. The philosopher and neuroscientist Raymond Tallis mounts an all-out assault on those who see neuroscience and evolutionary theory as holding the key to understanding human consciousness and society. While fellow scientist Barbara Sahakian explores the ethical dilemmas which arise when new drugs developed to treat certain conditions are used to enhance performance in the general population. And the gerontologist Aubrey de Grey looks to the future when regenerative medicine prevents the process of aging."

Available for listening here:

http://www.bbc.co.uk/programmes/b0122szw

Podcast here: http://www.bbc.co.uk/programmes/b006r9xr

 

Admittedly this is a more populist approach to the issues then we're used to, and there are a few moments where the guests make statements we would find a bit silly. But it seems to provide a very good summary of the issues for a lay audience, and an excellent defense of the moral importance of life extension. 

Thoughts?

There's a good song by Eminem - If I had a million dollars.  So, if I had a hypothetical task to give away $30 million to different foundations without having a right to influence the projects, I would distribute them as follows, $3 million for each organization:

1. Nanofactory collaboration, Robert Freitas, Ralph Merkle – developers of molecular nanotechnology and nanomedicine. Robert Freitas is the author of the monography Nanomedicine.
2. Singularity institute, Michael Vassar, Eliezer Yudkowsky – developers and ideologists of the friendly Artificial Intelligence
3. SENS Foundation, Aubrey de Grey – the most active engineering project in life extension, focused on the most promising underfunded areas
4. Cryonics Institute – one of the biggest cryonics firms in the US, they are able to use the additional funding more effectively as compared to Alcor
5. Advanced Neural Biosciences, Aschwin de Wolf – an independent cryonics research center created by ex-researchers from Suspended Animation
6. Brain observatory – brain scanning
7. University Hospital Careggi in Florence, Paolo Macchiarini – growing organs (not an American medical school, because this amount of money won’t make any difference to the leading American centers)
8. Immortality institute – advocating for immortalism, selected experiments
9. IEET – institute of ethics and emerging technologies – promotion of transhumanist ideas
10. Small research grants of $50-300 thousand

Now, if the task is to most effectively invest $30 million dollars, what projects would be chosen? (By effectiveness here I mean increasing the chances of radical life extension)

Well, off the top of my head:

1. The project: “Creation of technologies to grow a human liver” – $7 million. The project itself costs approximately $30-50 million, but $7 million is enough to achieve some significant intermediate results and will definitely attract more funds from potential investors.
2. Break the world record in sustaining viability of a mammalian head separate from the body - $0.7 million
3. Creation of an information system, which characterizes data on changes during aging in humans, integrates biomarkers of aging, and evaluates the role of pharmacological and other interventions in aging processes – $3 million
4. Research in increasing cryoprotectors efficacy - $3 million
5. Creation and realization of a program “Regulation of epigenome” - $5 million
6. Creation, promotion and lobbying of the program on research and fighting aging - $2 million
7. Educational programs in the fields of biogerontology, neuromodelling, regenerative medicine, engineered organs - $1.5 million
8. “Artificial blood” project - $2 million
9. Grants for authors, script writers, and art representatives for creation of pieces promoting transhumanism - $0.5 million
10. SENS Foundation project of removing senescent cells - $2 million
11. Creation of a US-based non-profit, which would protect and lobby the right to live and scientific research in life extension - $2 million
11. Participation of  “H+ managers” in conferences, forums  and social events - $1 million
12. Advocacy and creating content in social media - $0.3 million