Fight Aging!

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!