Longevity Convergence
Posted by Jeriaska on March 12th, 2009
Convergence08, the interdisciplinary unconference, continued with a panel discussion on life extension. Moderated by Christine Peterson of Foresight Nanotech Institute, the group of biotechnology and health experts included Aubrey de Grey of the Methuselah Foundation, Terry Grossman of the Frontier Medical Institute, Bruce Ames of the Children’s Hospital Oakland Research Institute, and Gregory Benford of Genescient Corporation.
The following transcript of the Convergence08 Longevity panel has not been approved by the speakers. Video is also available.
Longevity Convergence
Christine Peterson: We really have four ambitious individuals up here in terms of their longevity goals. Why would you get someone up here that does not have ambitious longevity goals? Our first panelist will be Professor Bruce Ames of molecular biology at UC Berkeley, very well known to many of you. He is the inventor of the Ames test. If any of you learned about it in school, this is the Ames of the Ames test. His research is focused on cancer and aging.
Bruce Ames: I was a professor at Berkeley for many years, and now I am at Children’s Hospital Oakland Research Institute. My interests have gotten more medical. I am interested in preventative medicine and worked for many years on DNA damage, how to detect it, and what is important in humans for its prevention. Then we got interested in aging because all of our medical expenses are from these degenerative diseases of aging that come at the end of your life, such as cancer, heart disease, cognitive dysfunction and stroke. If we really want to have an impact on that, we have to work on the mechanism of aging.
We did a lot of work on mitochondrial decay. I am too old to wait around three years while a rat gets old. Mitochondrial decay is something you can get your hands on, and we published 35 papers or so on mitochondrial decay in aging. A terrific post-doc and I came up with normal biochemicals used in the mitochondria that delay mitochondrial decay and made the old rats more like young rats. I founded a company called Juvenon that sells these pills and put all my stock in a foundation so that I have no financial interest.
In the last few years, another thing going on in my lab is work in micronutrients. I am interested in what is optimal nutrition, and we stumbled on something that has great relevance to aging. The principle is that there are 40 micronutrients—about 15 minerals, 15 vitamins, about eight essential amino acids and two essential fatty acids. If you do not get any of these 40 substances, you die. What nature has built in, we suddenly realized, is a system for dealing with shortage. Nobody worries that 60% of the country is really low on magnesium. Magnesium is in the center of the chlorophyll molecule, and every time you eat a big plate of spinach you are getting your magnesium. 60% of the country is really low in it.
It turns out that what happens as you get low in magnesium is that you get rid of a lot of your metabolism, all the long-term stuff. Basically, it ages you faster. Through all of evolution, animals have been running out of nutrients, so it is a trade-off between survival and long-term stuff. Whenever you are short of any micronutrient, it ages you faster. We are talking, I think like 90% of the country. There are not too many people eating a balanced diet, and the big disaster was sugary soft drinks, potato chips and all these high calorie foods that have no nutritional value. We are not getting enough Omega-3′s or enough magnesium. Not many of us are eating a perfect diet.
Peterson: Our next panelist, Dr. Terry Grossman, is a medical doctor. He is the founder and medical director of Frontier Medical Institute. Most of you know his name because he is the co-author with Ray Kurzweil of the book Fantastic Voyage: The Science Behind Radical Life Extension.
Terry Grossman: Thank you very much. I am a practitioner of anti-aging medicine, so the disease that I treat is the disease of aging. Most people are accustomed to thinking of aging as a natural process, but I like to differentiate between aging the disease and growing old as a natural process. All of us grow old, and we are a few minutes older than when Bruce started speaking, but we have not necessarily aged during that time. It really has to do with the lifestyle choices that we make on an ongoing basis that determines whether or not we age as we grow older.
For instance, if we helped ourselves to some of the foods that were on the snack tables earlier this afternoon, we possibly underwent some aging. For instance, I spoke with someone today who had a sugary breakfast, some bacon and eggs, whereas I had some fruit and green tea for breakfast. I think that by making proper lifestyle choices it is possible to grow older without aging. It is possible to do that at many ages. We can look at children between the ages of 5 and 15, and they have aged ten years between that span, yet 15 year-olds are in many ways healthier than 5 year-olds. They are ten years older, but they have not experienced much in the way of aging. 15 year-olds have much higher levels of anti-aging hormones like testosterone, estrogen, DHA and growth hormone.
It is much more difficult to do the same thing between the ages of 65 and 75, or the ages of 75 and 85. In fact, the aging process is largely due to lifestyle choices that we make. I feel that by making proper lifestyle choices it is possible to grow older without aging at any age.
Aging has one purpose, and that is to destroy our health and to result in our death. The thing about aging is that if we look at it as a disease, it is unique in that it afflicts 100% percent of us and has so far proven to be 100% fatal. It is well worth our attention.
The fact is that aging has been introduced at an earlier age as an elective. If we look at our sperm cells and our egg cells, they are actually immortal. Sperm cells and egg cells do not age. If we keep these cells in a petri dish, provide them with nutrition and remove their waste products, they will live forever. As soon as they join with egg cells and form a new life, then the aging clock begins to tick and mortality begins. It really is an elective process that has been imposed upon us.
My philosophy in respect to longevity and aging is expressed I think in the titles of the three books I have written. The first was called The Baby Boomer’s Guide to Living Forever, the second one with Ray Kurzweil was called Fantastic Voyage: Live Long Enough to Live Forever, and the third one, which is going to be coming out in April, is called Transcend: Nine Steps to Living Well Forever. There’s a common theme here.
None of these books is called “How to Live Forever,” because the bottom line is that we do not know how to do that. However, what Ray calls “the law of accelerating returns” means that technological change is happening very rapidly, and biological change happens linearly. By linking technology and biology we can essentially reprogram our biochemistry such that we are able to take advantage of that rapid technological change. Our genes today are essentially the same as they were 40,000 years ago. They were well suited for a world of scarcity, where starvation was constantly on our doorsteps. Whereas we live today in a world of abundance, although looking at what has happened with the stock market in the last couple months we may be half as abundant as we were.
Nonetheless, things are better than they were in the past. I think now we are at the inflection point. Exponential growth looks flat for a long time until you reach the knee of the curve and then you think it is exponential, but it has been exponential all along. I think right now, with respect to aging and longevity, we are right at the knee of the curve and dramatic increases in the acceleration of lifespan will be available to us in the years ahead.
Peterson: Our next panelist you will remember from this morning, Dr. Gregory Benford of UC Irvine. A physicist originally, many of you have read his fiction. He has moved into a field related to treating longevity and is the founder of Genescient.
Gregory Benford: Yes, I am not actually a biologist, I just play one on panels. I spoke this morning about the general strategy of my company Genescient. I thought today I would talk more generally about what you do when you have acquired a lot of genetic information, as Genescient has.
We read the genomics of these long-lived fruitflies that lived about four and a half times longer than the control flies. The biologists thought we would get about fifty useful genes, SNPs. We planned on carefully parsing through all of them. When we ended up with around 750, the plan went out the window. We realized that the whole process is far more complex, with multiple pathways, multiple disease targets and overlaps that we had not suspected.
I mentioned this morning that we were very surprised to find that Alzheimer’s genes in many ways overlapped with diabetes Type 2 genes. We went to talk with the clinical people and they knew that diabetes Type 2 was predictive for Alzheimer’s. That was news to us. We discovered it in reverse by going through the genomics. To me, playing a biologist on a panel, this was a real surprise, to discover something from the raw data instead of from the clinic. The real message was with regards to the real use of this information. We started out thinking that we would begin with a genetic diagnostic. It turns out that it is not as broadly applicable or as profitable as people on the street would like to have.
What people want is something they can take to make their lives better, to make them live longer, to augment their genes in the defense against these results of aging. That is why we chose this path. At the same time it also means that you have choices of how to filter the information. One strategy is to screen people’s aspirations, things that they want to test. You can provide a service for telling people what pathways to go down to and therefore intersect their interests. After all, we have this curious habit where diseases are kind of broken up into interest groups. There are whole foundations for diabetes, Alzheimer’s and so on.
Many of you know that Terry Pratchett was diagnosed with Alzheimer’s last year at the age of 57, and he has been going through this process of documenting publicly what it is like to feel yourself accelerating along this curve. He turned around and gave a million dollars to the Alzheimer’s Foundation in the UK. Later he asked me, what impact did I think it would have on his life. I said, to tell you truthfully, I’m not sure it will make a difference because their plans are long-term. I think what everyone really would like to see is a faster path than “Let’s do some more R&D.”
I am glad to see us actually have an open discussion on what to do. Moore’s Law and the advance of genomic readers has given us more and more information, and I am beginning to regard this field as an information management problem. What do we use it for and what is the best path? Honestly, one of the reasons I am at this meeting is to find out how to use it.
Peterson: Great, thank you, Gregory. Our fourth panelist, Dr. Aubrey de Grey, is best known for his work on SENS, which is Strategies for Engineered Negligible Senescence, and his involvement with the Methuselah Foundation.
Aubrey de Grey: Thanks very much. As Christine said at the beginning, I guess I cannot claim to be the most ambitious of the people up here, but in a way that is because I am the least optimistic about the less ambitious approaches that are being pursued by my colleagues here on this panel and by many other people. In Terry and Ray’s book Fantastic Voyage, there is what they call three bridges to the comprehensive defeat of aging. In a way, there is a bridge zero that they did not mention, which is the approach that is taken by the enormous bulk of the medical community who are interested in addressing the problem of aging.
Of course, one of the biggest reasons why Terry Pratchett’s million pounds is probably not going to make much difference to his life is not simply that the research that we have funded is not long-term, but that there is actually already an enormous number of millions of dollars already being applied to Alzheimer’s research specifically over the developed world, added to all the other diseases of aging. The difficulty with that approach to combating these things is that by the time these diseases have gotten far enough along to actually be called diseases, things are getting pretty far out of hand and chaotic, especially since many of these diseases may be happening simultaneously, exacerbating each other and generally making the whole thing pretty intractable.
The real reason why what I call “the geriatrics approach” to combating aging is intractable is simply because it is not applying the really rather reliable principle of “prevention is better than cure.” Essentially the targets for these interventions are consequences of stuff that is going on throughout life and progressively accumulates to result in various types of molecular and cellular damage that are side effects of our normal metabolism. As people get older, those side effects continue to accumulate. If you are attacking the side effects of those consequences, namely those particular diseases, then your job is just going to be getting harder and harder as time goes by. This geriatrics approach is therefore going to be a short-term approach, and a losing battle.
Of course, Ray and Terry wrote very openly about how we can apply the principle of prevention being better than cure by identifying changes to the diet, taking supplements and so on, that may, if you like, clean up our metabolism—stop it from laying down these various molecular and cellular side effects quite so fast as it normally would. That is very much the sort of approach that people in academia who study the biology of aging also tended to gravitate to, and the work that Bruce mentioned is a fine example of it.
I feel those approaches are very valuable in principle, but my sense is that they are not going to give us very much. Essentially, the body is very well tuned, and with the exception of the work that has been done more recently that Bruce mentioned, the compensation for magnesium deficiency, it is going to be pretty difficult to get all that much extra healthy life for people who are already doing pretty well. I think it is going to be hard to improve those people’s lives by the gerontology approach of trying to clean up people’s metabolism. For this rather pessimistic reason, I gravitate myself to the view that we need a third approach that is more preventative than the geriatric approach, but somehow avoids the enormous amount of ignorance that we still possess with regards to how cells work, let alone how whole organisms work, and how these various forms of damage accumulate.
That was what led me to believe that actually we might be better off trying to apply regenerative medicine to the problem of aging. In other words, let these various forms of molecular and cellular damage be laid down at the rate that they are naturally laid down—so that you do not have to understand how they are laid down—but then clean them up before they start to lead to diseases of aging. This can be called a regenerative approach because it is essentially restoring the structure of the body at the molecular and cellular level to something like what it was at a younger age when less damage had accumulated.
Various things that I think we are going to need to do to make this sort of thing work involve what would be called classical aspects of regenerative medicine—things like stem cell therapies, tissue engineering maybe, certainly a variety of different applications of gene therapy. There will be other things that you may not ordinarily think of as regenerative medicine, but would certainly come under that strict definition that I gave a moment ago.
I guess the main reason why I have become quite optimistic, indeed why Terry and Ray recapitulated a lot of my work in Bridge Two of the book that they wrote, is because I think that regenerative medicine has now come far enough, and also our understanding of these various types of damage has come far enough that they have become practical—not yet, but in the foreseeable future—to apply pretty comprehensively the regenerative approach to the concept of aging.
That is the work that I focus on, and that is the work that the Methuselah Foundation focuses on. I think we have a pretty good chance of developing proof of concept experiments in the laboratory in mice within the next ten years that will demonstrate that approach is feasible by taking middle-aged mice and rejuvenating them thoroughly enough to give them a couple extra years of healthy life. I do not know how long it is going to take to translate that technology into humans because we are talking about the relatively distant future, where technology is hard to predict, but I think we have a 50% chance of getting there within 25 or 30 years.
Because these therapies are bona fide rejuvenation therapies, repair therapies that actually restore people to a younger biological age, that means that all of us in this room have a fair chance of benefiting from that approach. So, I’ll stop there.
Peterson: Great. Thanks, Aubrey.
Ames: Maybe I’m prejudiced, but I think there is a tremendous amount we can do by improving our diets. Micronutrients are dirt cheap. They really do not cost anything. Minerals and vitamins are cheap, and even Omega fatty acids in the form of fish oil are cheap. If we had the right information, we could tune up everyone in the world inexpensively.
Already I think we know enough to help the poor, who are eating godawful diets. They are going to get cancer and die early of diabetes. Obesity is a disaster for the health. There are forty or so different diseases tied to it. At some point thin people are going to rebel and not want to pay for all these medical costs. Obese people are amazingly deficient in everything. Their diet is sugary soft drinks, donuts and things like that. They are hungry all the time, but we are working on that.
Peterson: Okay, so, take micronutrients? Eat as healthily as you can, and if you need to lose weight, lose weight?
Ames: Exercise, don’t smoke…
Peterson: Wear your seat belt. Terry, what would your average middle-class person do?
Grossman: Well, begin with the things that are free. Like Bruce said, it does not cost more to eat healthy. Eating more vegetables or to exercise does not cost more. You can get a gym for ten dollars by buying rubber band. That is what I bring with me when I travel. They weigh a few ounces, and instead of spending $90 a month to join a gymnasium, you can walk, jog or ride a bicycle. Something you can do that will actually save you money, so it is a positive for your budget and will extend your life, is to reduce your calories. Caloric restriction has been found to extend life in animal species, and there is a lot of suggestion that it makes people healthier. You will save money by eating less.
Cutting calories even ten to twenty percent makes a big difference. I think most of us over the age of thirty should at least take a multiple vitamin/mineral, should take some supplemental fish oil, and should have our vitamin D levels checked. Many of us are low on vitamin D above and beyond our multiple vitamin/mineral. As far as testing goes, the number one cause of death in the U.S. at least is heart disease. There is a test now available called coronary artery calcium score, a CAT scan, which costs between $250 and $300. You do not need a doctor’s prescription to get it. It will screen you and tell you if you have any amount of build up of this cholesterol plaque in your coronary arteries.
You need to know that. If you have not had a coronary artery calcium score done yet and you are a woman over the age of fifty or a man over the age of forty, give serious consideration to getting one of these as a baseline for a few hundred dollars as part of your budget. Also, follow the appropriate cancer screening. Colonoscopies after the age of fifty, either thermography or mamography for women, and PSAs for men. That is really the low-hanging fruit that does not cost a lot of money and I think will translate into some significant benefits for the majority of people.
Peterson: You did not mention this but I have a couple of friends who actually go to you as their physician in Denver. If you do not have a longevity doctor now, you can go. I don’t know if you have any space on your schedule, but Terry is in Denver.
Grossman: There are several of my patients in the audience.
Benford: I will just make one observation. The faculty at UCI, particularly the physics department, there is a window that people go through between forty and fifty when they essentially give themselves permission to grow older, get fatter and they really go away. It is a psychological state. The game’s not over, but you can just sit and watch it. I have found in some of my friends, one of whom died very recently, that it is a phase transition they do not survive for very long. They really go downhill quickly. It is a psychological barrier, not a physical one.
Peterson: Great point. My guess is Aubrey is not going to tell us not to do these things. Of course he is going to tell us to do these things. He has a somewhat distant perspective on how do we take money and convert it into longevity.
de Grey: I would absolutely like to applaud all the things that were just mentioned. I think that some of these things cost a little bit of money, but if you are a bit creative you can make sure that you do not, as Greg just said, end up giving up all your intellectual activity, which is an extremely bad thing to do.
When you ask what can a middle-class person do to change the game, so to speak. I tend not to think of these things personally, but think in terms of how many lives I can save by hastening the defeat of aging. However, to answer the question, I would say that there is an awful lot that can be done just to raise awareness of the potential for major breakthroughs in combating aging in the foreseeable future, in terms of making serious benefit to the healthy longevity of people who are alive today. I think that even though most people are not scientists, are not biologists, or not in the position to directly get involved in the research, there are plenty of ways in which people who are in the middle income bracket can get involved in advocacy, especially in raising the legitimacy of discussion about the possibility of doing something serious about aging.
The sorts of things that I tend to emphasize are to make sure that people don’t change the subject. Make sure that people don’t carry on thinking that this is all about longevity for the sake of longevity, when in fact it is all about keeping people healthy and not getting sick, which is something rather hard to argue against. Advocacy does to some extent cost money if you want to make a big difference to a lot of people. I think this is something that young people in the audience would have the highest probability of benefiting the most from.
Coming back to the things that were mentioned earlier, there are all manner of creative ways of making a difference to people’s lives, such as spending a few hundred dollars a year buying multivitamins for a hundred or a thousand people in your local poor community, for example.
Ames: Costco sells 400 multivitamin/mineral pills for eleven bucks. It’s really cheap. However, a multivitamin is not quite good enough. It does not have enough magnesium, calcium, or potassium, which would make the pill much too big. It does not have Omega 3s, which is in fish oil. It does not have fiber, which is important for gut health. We made a bar that I think will do all those things, has very few calories and tastes good. It took us a couple years.
A lot of it is motivation. It is easy to not exercise. My wife is Italian and she feeds me a wonderful Mediterranean diet, but she kept nagging me that I should get more exercise. One day I told her that I get plenty of exercise: I run my experiments, I skip controls, and I jump to conclusions. I like that joke so much I must have told it fifty times. She said, “I’ve heard enough of that damn joke—I’m taking you to a personal trainer.” Now I go a couple of times a week and lift weights, row and do all the things that I know are good for me. Single men have an eight year shorter life expectancy than married men. Both men and women know why. Single men self-destruct.
Convergence: Longevity Panel
