Closing in on the Cure for Death
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Time is on your side if you're under 30, suggests biogerontologist Aubrey de Grey in an optimistic discussion of healthy life extension. With more than 20 first-author publications in the past six years, de Grey is a leader in turning healthy life extension hopes into reality. This article is based on an interview by Shannon Foskett originally published at Betterhumans. You can find out more about Aubrey de Grey's work at the SENS Foundation.

Copyright © Aubrey de Grey.

Indefinite Healthy Lifespans, When?

I am bullish on the prospects for indefinite lifespan. If you're interested in living a far longer, healthier life, I think the discussion here should offer reasonable ground on which to build a case for true healthy life extension. In my opinion, there will be only a short interval between the time when we first have genuine life extension treatments and the time when we're improving those treatments faster than we're aging.

My personal research goal is to achieve an indefinite lifespan for human beings, and I think we have a fair chance of doing it in about 25 years with the right funding.

Given the present research and political environment, the actual timeline for achieving the first real healthy life extension breakthroughs could be anything from 15 to 100 years. Of course, we should all work hard to keep to the lower end of that range! By "real" I mean treatments that at least double the remaining life expectancy of averagely healthy 70-year-olds. Treatments that do more will very probably follow rapidly -- more rapidly than aging is occurring. For practical purposes we will by then have reached the cusp where individuals with the physiology of present-day 70-year-olds or younger will have an indefinite lifespan.

There is something important to say about these numbers. Most of my colleagues absolutely refuse to give timelines or expected results like this, because they feel that no such statement can be scientifically defended. Hence they feel that providing an answer is to misuse their exalted status as scientists. I would agree with this in all areas of science that are not medically relevant, but not in medical areas. I feel that those people with the best information have a duty to state their best-guess timeframe, because that information determines choices in life, lifestyle, medication, and so forth for everyone.

I know I can't defend the above numbers robustly but I don't regard that as a justification for silence.

Should We Extend Our Lifespans?

There is a strong consensus in the research community to step up the pursuit of healthy life extension. Only a few holdouts, most prominently Len Hayflick and Robin Holliday, currently dispute this. Most researchers feel, quite correctly, that postponing (and ideally reversing) aging is the only plausible way to reduce the vast number of people suffering from age-related disability and disease.

Despite unity in the desire to move forward, there really isn’t consensus regarding the feasibility of various branches of life-extending medicine. Opinion in the field is splintering. I'm more or less the only scientist to publicly talk about expectations and research for an indefinite healthy human lifespan, but privately a lot of us think that considerable progress is not all that distant.

In a piece soon to be printed in the Journal of Antiaging Medicine, a Dutch journalist named Theo Richel reports on a telephone survey of 64 mostly senior biogerontologists. He reveals that at least 20% thought it likely that someone would reach 150 years of age by 2100 and that the average lifespan of those born in 2100 would be 200 or more. Notice that this implies our 150-year-old-to-be is already 53 this year.

Pursuing the End of Aging

While I am not the only scientist dedicated to healthy life extension research, I am the only one addressing all of the components of aging at the same time. Some of these individual components (such as cell loss, which receives a lot of attention) are the sole subject of research by prominent scientists who do call themselves gerontologists. These researchers know they are only working on one aspect of aging and they don't know (or have much to say, at least) much about other parts of the field.

At the present time, I believe I am the only biogerontologist to address healthy life extension in a way that has a fair chance of success in the near future. Quite a few of my colleagues (such as Guarente, Kenyon, Spindler, Roth, Ames, Perls) have started companies to develop age retarding drugs. This is, of course, not because they want to make money with products that don't work, but because they really do think they can develop such drugs in a short time frame. Unfortunately, I am perfectly sure that the approaches they are taking will yield only a year or two of extra life, if that. The whole idea that we should focus on reversing aging rather than slowing aging is turning out to be terribly hard for my colleagues to take on board. I'm getting there, though. In science, so long as you are friendly and listen to your colleagues, other researchers will eventually listen to your ideas. If your ideas can then stand up to challenges and wider scientific debate, a larger group will accept them.

It's not that my colleagues don't care, it's that they can't see how to proceed. They’ve been unable to see for so long that it's taking time for them to appreciate a way to proceed when it is laid out in front of them. This is quite the normal way of things for all sciences. It can take a decade to get the scientific establishment to move on from a firmly entrenched theory, even if data falsifying the theory is clearly there for everyone to see.

Working Against the Grain

While I am admittedly working against the grain of the biogerontology field, I am optimistic about the ultimate success of real healthy life extension. My detailed plan of implemention has been scrutinized by many of my colleagues in biogerontology and not found glaringly wanting. Funding, obviously, is still lacking, or you would be hearing more from me!

Overviews of my proposed research and have been published in two main forms: one aimed at a scientific audience and one for a wider audience.

The Seven Point Plan

The way to cure aging is to rejuvenate tissues, not to try to slow down their deterioration. It seems that the technically hard requirements for rejuvenating tissue are also necessary if you want to simply slow down tissue deterioration. Intuition says that reversing aging must be much harder than slowing it down, but intuition is wrong.

There are seven main topics that we need to address in producing working healthy life extension medicine aimed at indefinite lifespans.

  • A cell therapy to restore the number of cells in tissues that lose cells with advancing age, like the heart and some areas of the brain.
  • Targeted (homologous recombination-based) gene therapy that will delete our telomere elongation genes. This will stop cancer development. Some rapidly renewing tissues such as blood, skin and gut require telomere elongation, however, so a cell therapy must be developed to account for this need.
  • Normal (insertional) gene therapy that will introduce modified versions of our 13 protein-coding mitochondrial genes into nuclear DNA. This will prevent accumulation of mutations in the mitochondrial DNA from affecting us as we age.
  • Normal (insertional) gene therapy to introduce bacterial or fungal genes that can break down damaging chemicals and proteins that the human body currently cannot handle. These include the oxidized cholesterol that causes atherosclerosis, A2E that is responsible for macular degeneration, and malformed proteins in the brain thought to be responsible for Alzheimer's, Parkinson's and other neurodegenerative diseases.
  • Immune therapy to destroy senescent cells. Senescence in cells is an undesirable state that occurs to cells in culture after dividing many times. Our bodies don't accumulate very many senescent cells, and they're of cell types that renew easily. Tailoring our immune systems to destroy cells as they become senescent is quite sufficient.
  • Immune or small-molecule therapy to disaggregate or engulf the junk material known as amyloid that accumulate outside cells. Amyloid is prominent in the brains of Alzheimer's sufferers, but slowly accumulates in all of us as we age.
  • Small-molecule therapy to break glucose-derived crosslinks that form randomly between long-lived molecules in the extra-cellular matrix, such as collagen and elastin.

All of these projects are underway somewhere in the world and to some extent. You can visit my website for more details. I am a not a lab worker, so my primary ongoing research goal is to facilitate these projects. This means getting people together, making scientists aware of one another's work and getting them to understand why these projects matter so much. This facilitation and coordination is a big job, because biology is such a large field that most experimental scientists are not aware of half the places in which their work would be relevant. Most of the leaders in the projects I have listed above are not biogerontologists and are performing this research for reasons totally unrelated to aging.

Beyond facilitation within the scientific community, I spend time on advocacy and explaining to the public that a real, concrete plan for fixing aging now exists. This sort of dialog with a wider audience is essential to obtain the level of funding that this research plan requires: about US$1 billion over 10 years.

Scientific and Technological Challenges

Setting aside funding issues for the moment, each of the seven points listed above presents technical obstacles and challenges. None are insurmountable, however. At this stage, only targeted gene therapy is known to be very hard to do, and there has been quite a bit of progress on that in recent years.

There are issues with what I see as current wrong directions in research. These take time, funding and effort away from more valuable paths forward. An example is the fixation most biogerontologists have on comparing long- and short-lived species in order to understand how to extend human lifespan. This is amazingly over-simplistic; no engineer with a good biogerontology background would give it the time of day.

Social and Political Obstacles

In my view, there’s really on one root social and political obstacle to funding ambitious healthy life extension research. This one obstacle is fatalism; skepticism that anything can be done about aging in time to make a difference to you and me personally. All the nonsense we hear from the Leon Kasses and Francis Fukuyamas of the world about how terrible it would be to cure aging is just a smokescreen. People only take it remotely seriously as a way come to terms with what they see as inevitably short lifespans.

The fatalism problem can be dissected into three separate components that form a sort of triangular logjam, each perpetuating the next.

  • The public thinks nothing can be done to cure aging.
  • Seeing public opinion, politicians will direct government funding in small amounts and to very modest, unassuming work. Funding a project that would be perceived as an ambitious pipedream would jeopardize re-election, after all.
  • Scientists see the current funding environment and don't submit proposals for ambitious projects, even if they want to, because it's a waste of time -- the proposals will be turned down. When scientists talk to the public, they talk about the cautious projects that are being worked on, rather than about the ambitious projects that they want to work on. This tends encourages the scientists themselves to adopt a mindset of shying from ambitious work in the first place.
    Given the way in which scientific work is presented to the public (modest and cautious, rather than ambitious) the public continues to view a cure aging as very, very far away. The scientists with the best information are telling them just this by restricting themselves to the modest, cautious line of delivery. Each of these three communities – public, government and scientific -- is behaving very reasonably in its own terms, but the end result is stasis.

Things are not quite as bad as they once were. Since researchers started to demonstrate interventions that produce very long-lived worms, we now have people talking about timeframes for developing age retarding drugs. Unfortunately, their credibility is impaired because they are only talking about adding 10 or 20 years (and the case for anything more than a year or two is in fact very weak) and b) they base this view on their work on worms. No mammalian biogerontologist is yet saying these things based on current research.

Taking all this into account, I view philanthropy as the way out of this stasis. Without meaning to be frivolous, scientists will do anything interesting for food. Injecting serious money into the field would unlock the logjam I have described here. It has to be real philanthropy though. The right work will take 10 years to succeed even in mice, 25 years in humans. Typical market venture funding biases work towards short-term goals, five years or less, and such biasing will mean that the right work will not occur.

A Prize for Anti-Aging Research

The Methuselah Mouse project is my way of breaking the fatalism logjam by making healthy life extension research on mice more interesting to the public. The approach I've taken, in partnership with the entrepreneur David Gobel, is to institute a prize for unprecedentedly long-lived mice. My hope is that by couching this work in terms that the public is comfortable with, I can get people to pay more attention to healthy life extension research in general and maybe escape their fatalism.

The type of work I hope the prize will encourage is late-onset interventions to repair or obviate accumulated molecular and cellular changes in already aged mice. This is the sort of research that is most relevant for human use. The seven treatments I mentioned earlier should, in combination, allow us to take two-year-old mice with a normal life expectancy of three years and make them live at least three more healthy years. This would certainly be something!

This goal should be possible within about 10 years with adequate funding, which I estimate at no more than US$100 million per year. Unlike the numbers for humans, I'm confident of this 10-year prediction because there are no arbitrarily hard problems to solve. In the case of human healthy life extension, safety matters mean that there are unknown levels of difficulty associated with research, particularly where it relates to gene therapy.

I regard this as the main goal of my work. It is impressive enough to make the public realize that human aging might be cured soon, and that's all that's needed to create greater funding that will translate these technologies to human patients. We can look at cancer as a precedent for this sort of activity. Fighting cancer turned out to be a lot harder than Nixon said in 1971, but awareness of cancer and the march to a cure is out there and money hasn't stopped flowing.

Immortality and the Prospects for Indefinite Healthy Lifespans

Talking about scientific research and healthy life extension inevitably brings up the question of immortality: the possibility that one could live forever if one wanted to. Immortality is a word that is often used imprecisely, but there is a big difference between an indefinite and infinite lifespan. If we fix aging completely but we still die of accidents and so on, our lifespan is indefinite but not infinite. An infinite lifespan is physically impossible, and I don't like using "immortality" to describe an absence of aging.

With regard to indefinite lifespan, defeating aging, I am optimistic. I think there will be only a short interval between the development of genuine healthy life extension treatments and the time at which those treatments improve faster than we're aging. This is all that's necessary to give us an indefinite lifespan. We currently have no idea what sort of treatments we'll need to keep us going when we're 200, but that's fine, because we have 100 years of research and development time. So long as we look carefully for signs of trouble in 180-year-olds as soon as we have any, and also at 80-year-old chimpanzees once we have them (which will be sooner, of course), we'll have time to head off that trouble before it kills anyone.

Getting Involved

There are plenty of ways for people to get involved in the development of healthy life extension medicine. For most people, I encourage you to point your friends towards this article. Talk to your friends, family, colleagues about what life would be like without aging. Visit sites like the Longevity Meme, Betterhumans and the Immortality Institute. Listen to what they have to say and follow their lead in promoting the concepts and ideas of meaningful research that will lead to a cure for aging. I also encourage you to donate modestly to the Methuselah Mouse Prize fund; it’s a great way to make a meaningful contribution to your own future health and longevity.

If you're a biologist, come to our conferences. Read my papers on the technologies we need to develop in order to cure aging. Start working on your favorite one and let me know, so that I can put you in touch with others who are working in the same area.

If you're a journalist, please do come to our conferences and write about my work. Most importantly of all, interview senior, high profile mainstream biogerontologists and ask them to explain why they don't think my approach will cure aging in the near future.

If you're an engineer, computer scientist or other technical professional, learn some biology. I started out by making well-received contributions to biogerontology after reading the literature for a few months. Perhaps I was lucky, but it is also the case that scientists in any given field benefit from different perspectives, training and mindsets. Don't take the easy way out by thinking that you can't help just because you don’t have the right expertise!

If you're wealthy, contribute significantly to the Methuselah Mouse Prize fund, and ask me what research you could productively fund. If you're extremely wealthy, ask me more about the proposed Institute of Biomedical Gerontology.

If you know someone fitting any of the above descriptions, have them read this article!

Comments

Already been seven years, I wonder why there was no comments here.

Posted by: Tannen at October 6, 2011 1:06 AM

I am 20 years old. I decided a year ago to become a biomedical scientist for this exact purpose. I have my reasons. To me death should be looked at as a disease. One in which our people only accept because it has survived for so long, therefore many say it is natural. What else could one say about something that is "inevitable". I hope to give us a choice. We make big decisions every day. Why shouldn't we be able to govern this as well? I will throw my life at this if I have to. If I personally don't succeed, I'm sure I will make many useful discoveries in aid to curing death. I have strong faith there will be many after me.

Posted by: Andy Baker at October 31, 2011 10:48 PM

I am whole heartedly behind the goals of this ambitious project. While I don't have a ton of money, or schooling in this field, to help, fairly soon I will. I'm an entertainer and performer, so I hope to have this prject helping me before ky muscles, and hard earned talents atrophy.

Posted by: Paul Elliot Berard at November 1, 2011 3:36 PM

How can anybody take this article seriously when the author can't even spell 'ageing' ??

This is a joke, all of mother Earth's fauna is scientifically scheduled to expire at some point, it's all part of the balance - we ever discover a key to eternal life and not only will we suffer from overpopulation, but famine and poverty will follow.

Posted by: Dan at April 11, 2012 11:36 AM

@Dan:
"How can anybody take this article seriously when the author can't even spell 'ageing' ??"

American rather than Commonwealth spelling: surely reason enough for dismissal.

"This is a joke, all of mother Earth's fauna is scientifically scheduled to expire at some point, it's all part of the balance - we ever discover a key to eternal life and not only will we suffer from overpopulation, but famine and poverty will follow."

What does it mean that "all of mother Earth's fauna is scientifically scheduled to expire?" This seems like word salad. Something is scientific if it involves applying the scientific method, but your sentence offers no plausible candidates. Did "mother Earth" apply the scientific method to decide that all of "her" lifeforms should die?

What balance are you referring to? The Earth is in a severe state of thermodynamic disequilibrium, so "balance" is something that's usually not found in our everyday experience. I suspect that your idolization of "balance" is based on navel-gazing mystical woo-woo nonsense.

Overall, you present nothing more than an argument from lack of imagination. "This is the way of things for the creatures of earth, so it must remain so even in the face of locally unprecedented novelties like intelligent intervention." In spite of the facial invalidity of this argument, it can be refuted even more strongly from a factual orientation. Among other things, coppiced trees refute this. Trees have finite (but perhaps quite long) lifespans, but if maintained as coppices there is no apparent upper bound.

Posted by: Jose at April 25, 2012 7:59 PM

The biggest obsticle that needs to be overcome here is the mindset that life MUST end. a little more than 100 years ago, man thought flying, land travel faster than a horse (cars), space exploration,global communication and if I'm not mistaken, electric lights were all impossible! Now look what we have achieved. I remember when there was no such thing as the internet and mobile phones were giant bricks for the mega rich. The human mind is capable of solving ANY problem no matterhow difficult given the right time, money, and enthusiasm.

When I can help to acchoeve thos goal, you can bet I will do what I can. I am no scientist, I'm a aspiring film maker... I am writing a script about this very subject to help put this more into rhe public eye and maybe even donat a big chunk of profit (if I'm lucky enough) from the film to do my part. Hell yeah I want to live forever!

Posted by: Dennis Howard at April 26, 2012 2:52 AM

This is CRAP. U can't and never Cure Death and By all means u will die. PPl the dream about vampires and eternal life is Crap. We all gonna die someday and why not help the humanity as we can instead of becoming lairs like this dude

Posted by: U full of Crap at May 3, 2012 3:56 PM

Gene therapy and away we go. It's possible - will endeavour to hit this field of research soon.

Posted by: Biomedical Researcher at May 29, 2012 10:47 PM

it most likely will not be gene therapy but an invention. only time will tell

Posted by: willing text subject at June 11, 2012 12:42 AM

It's shocking to see how ignorant some people can be. If "mother earth" felt that all things should die, then why are there creatures on this planet that don't? Scientists know of at least a half-dozen or-so species that do not die of old age. And shockingly, they have not overwhelmed the rest of nature or even their own habitat; no famine has been created by the introduction of immortal species.

As for poverty, the current monetary system is in ruin anyway. With the advent of replicators, (future MakerBots) the only vehicle left for corporate profit will be intellectual property (hence the propensity for patent lawsuits) and raw materials. So we're in for a pretty rough century anyway....

Posted by: nonarkitten at July 8, 2012 3:04 PM

I think it's interesting, but my way of trying to solve it is different (keep in mind I'm 16 so if I have a few hole in my theory please point them out so I can try to account for them in the future when I can actually perform experiments upon my theory). I hypothesize that our agelessness lies within preserving the telomere and making it so that it doesn't shorten durning mitosis. This is what, I believe, determines how long we will naturally live. Once the telomere reach a certain length they prevent the cell from undergoing mitosis. So I'm trying to find a way to prevent this shortening of the telomeres in cells. The problem with this is that now, you're halfway toward cancer right? Yes, but caner also has two more major factors (in my opinion) in it that need to be addressed separately. First would be that cancerous cells don't have a function. I'm unsure if my trying to keep the telomere from getting shorter when cells undergo mitosis will result in this, so this will be left to the future. Please comment on this, ESPECIALLY if you can back this up with some scientific knowledge. (Please no people who argue the ethics of this, I'm not trying to be ethical, I'm trying to cure death. Don't want to help, keep comment to yourself and wait till' I have the cure to decide weather or not you'd like to die) Next would be the uncontrolled mitosis, how cancers cells undergo it at a fast and uncontrolled rate. I believe I may have to make a separate implant for this which would be able to control the rate of devision. When cells die, they release a signal to let other cells know they are dead. Other cells than divide to make up for this dead cell. I'm not certain but I believe cancerous cells ignore this signal and randomly divide without this kind of trigger. I would have to find what triggers mitosis and find a way to counteract it ( I believe it lie in either electrical impulses or chemicals released through the body) I'd be here all night trying to explain this and risk alot of my theory getting stolen by someone else but I feel I can share this much and grow on this part from the thoughts and ideas of people on the internet (fingers crossed) PLEASE comment any useful or interesting ideas on either your theory or what could help my build my theory into reality. Thank you.

Posted by: Branden Rossney at August 5, 2012 4:48 PM

Since it is late I will only make a quick comment. Im no expert on this matter either so I might be wrong. Anyways, telomere shortening is only a very small subset of the factors that constitutes to aging. It is quite feasible that most of the cells in our body can be replaced by the stem cells which actively restore their own telemeres, and giving non-stem cells the ability to regenerate their telomeres would be tedious, unnecessary, and would only increase the chance of getting cancer. My point is that working to promote the regeneration of telomeres is not that important overall. What these researchers are trying to do is to sustain the basic mechanical functions of our body by various intervening techniques in hopes to (assuming we have somehow defeated cancer) enable the regeneration of 'permanent cells' (ex. neurons, muscle), as well as the clearing of any factors that might inhibit the normal function of our body. This will only be achieve by a vast combination of present (including stem cell research, nanoscience research, genetic 'manipulation' research, and many many more) and maybe future methods.
There is no (at least for now) one type of target-specific treatment plan that can stall the aging process (or even bring about a modest, 50% inc. in human lifespan). It is, as I have come to realize, an extensive project that will take tremendous amounts of collaboration and time. As it stretches over so many disciplines, it will be a long time before people finally start to tie the knowledge together. It is only then that the project to life extension can shoot off.
I mean.. just look at the biological research being done at the moment (ex. nature)- they are all filled with (almost random) terminologies of whatever molecules or cell types they are studying... It is really hard to get a general sense of WHAT is going on lol
If I am incorrect on anything stated above, please correct me.

Posted by: Yunlong Yang at August 18, 2012 9:23 PM

I am 20 and whole-heartedly believe that aging can be cured as any other disease is cured. I know not how old the author of this article is, but I hope one day to be able to make a financial contribution to people like you. I also hope that the general consesus of the public will be that aging is a disease. My expertise is in the field of business ownership, but one day I hope my business will be profitable enough to make contributions to efforts made by you and others like you to promote the concept that we as humans can defeat this "death" that has plauged nearly every species in existence. Positive change only occures when people can think outside the box, and leave hindering mindsets at the curb.

Posted by: Austin at February 24, 2013 10:31 PM

i got no money education or exp to offer but if aging and death can be cured all i can say is i offer to be a guinea pig to help best ill ever be able to do to help

Posted by: george at June 28, 2013 12:27 AM

You can already cure ageing to some extent with good diet and plenty of excercise. If you eat plenty of low sugar, low starch, high protein, nutrient rich foods and do a lot of excercise you can slow down the ageing proccess a lot and remain fit, active and relatively young looking for decades. And there are already other ways to fight the ageing process such as hormone replacement therapy and cosmetic surgery. I see the things mentioned in this article additional way to fight ageing which will gradually come into mainstream use over the coming years. And I think that one day in the future ageing will be conquered. People think scientists that are trying to cure ageing are trying to defeat death, that is impossible, but they are trying to defeat the illnesses of old age. People will still die from a wide variety of causes like they do now, but they will no longer be affected by the debilitating effects of old age, remaining fit active and good looking indefenitely.

Posted by: Angus at August 17, 2013 1:14 PM

As of now, the most promising treatment to bring about aging reversal is gene therapy. This might be done by infusing a person with stem cells that are identical to ones they had at a young age. The goal would be to replace old (mutated over time) DNA in the body with effectively young DNA, by means of those special stem cells. It would probably involve a gradual process to reverse aging.

A way to get such effectively young stem cells could involve drawing a large number of stem cells from such places in the body as testicles, ovaries, bone marrow, or inner nasal area. Then the cells would be meticulously filtered to obtain ones that are effectively young, the portion that have, by chance, escaped the ravages of time. Those could then be multiplied and implanted into the body.

Hopefully that type of process or some other way to effectively un-age a person's DNA will become possible soon.

Posted by: JosephFA at September 17, 2013 4:29 PM

Wow there really are creatures on Earth that can live forever all they do is go thru a stage called trans transdifferentiation... Like some jelly fish I googled... So it's TRUE!! Immortality is possible for them so why not us???? Keep up the good work! Screw the damn ignorant people they can go on believing whatever they want but one day this will be achieved...

Posted by: Gus at January 2, 2014 4:24 AM
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