The Seven Lively SENS (Strategies for Engineered Negligible Senescence):
An Interview with Dr. Aubrey de Grey
Aubrey de Grey, Ph.D. is on a search for the Holy Grail of medicine–the ability to stop and reverse the human aging process. Although this ambitious biogerontologist at the University of Cambridge in England was trained as a computer scientist, he is also a self-taught biologist with a strong interest in why organisms age. After marrying a geneticist in 1991, Dr. de Grey became so interested in biology that he began teaching himself the subject. In 1996 he had progressed far enough to make a significant contribution in molecular biology, by identifying previously unknown influences that affect the mutations that occur in mitochondria (the intracellular structures that provide cells with energy), after only reviewing the relevant literature on this for several months.
Dr. de Grey received his M.A. in computer science at the University of Cambridge, and has been working there as a computer scientist in the Department of Genetics since 1992. His insights into mitochondria earned him a Ph.D. in biology from the university, although Dr. de Grey is not a laboratory researcher. He does no biology experiments. Rather, he is purely a theoretician in the realm of biology, and he prefers to see the Big Picture. By studying the literature from different scientific disciplines, he has assembled a master plan for how to “cure aging.” Although controversial, he has outlined what many experts believe are feasible engineering solutions to the seven basic consequences of prolonged metabolism that accumulate as what we call “aging.”
These seven factors involved in aging, and Dr. Grey’s proposed solutions, will be discussed in the interview, but briefly they are: (1) The loss of cells that we need; (2) The accumulation of cells that we don’t need; (3) DNA mutations inside the cell nucleus; (4) DNA mutations inside the cell’s mitochondria; (5) The accumulation of “junk” inside of cells; (6) The accumulation of “junk” outside of cells; and (7) The formation of cross-linked proteins outside cells.
For each of these seven problems Dr. de Grey has a solution. These solutions are organized as part of a project he has masterminded, which he calls “Strategies for Engineered Negligible Senescence,” or SENS. Two of these strategies are ideas of his own, while the other five came from colleagues. The strength of Dr. de Grey’s ideas lies in his engineering approach–which is goal-directed to find practical solutions–and his interdisciplinary perspective. What may be most important about Dr. de Grey’s work is that he has brought together many experts from different fields that normally wouldn’t be interacting and sharing ideas. It is through this cross-fertilization of ideas that so much excitement and controversy has resulted from his work.
Dr. de Grey is currently the chairman and the Chief Science Officer of the Methuselah Foundation, which offers financial prizes to researchers who can break previous records of lifespan in mice. He is on the scientific advisory boards for the Maximum Life Foundation, Legendary Pharmaceuticals, Centenarian Species and Rockfish project, and the Alcor Life Extension Foundation. Dr. de Grey is also on the Board of Directors of the International Association of Biomedical Gerontology and the American Aging Association, and he is editor-in-chief of the journal Rejuvenation Research. To find out more about Dr. de Grey’s work visit his Web site: www.sens.org
I interviewed Dr. de Grey on February 3, 2005. Aubrey is extremely attentive, mentally energetic, and eloquent with words. We talked about the reasons for aging, the obstacles that stand in the way of reversing the aging process, and the social and psychological consequences of having a population that lives for hundreds or thousands of years.
David: How did you first become interested in biogerontology?
Aubrey: This is one of the most common questions that I get asked, of course, but it’s actually one of the ones I find hardest to answer. I’ve been wracking my brains for years about this, because, you see, it was very gradual. I’m sure that from the dawn of time–from when I was a kid–it was obvious to me that aging was not a good thing, but that didn’t really count as being interested in gerontology because I never regarded it as my problem. I was not a biologist back then. My main interests in school–as a kid and as a university student–were in math and computers. I guess I took the view that while it’s obviously hard to do anything about aging there are professional biologists who must doubtless be hammering away at this, and they’ll make their breakthrough in the fullness of time.
So it was really only after I met my wife that I became interested in biogerontology. My wife is a geneticist, and she’s quite a lot older than me. She was already forty-five when we met. She was a full professor at UC San Diego and was on sabbatical here in Cambridge. It was really through, first of all, learning a lot of biology, just by accident, by just talking to my wife, that I began to reawaken this interest. I began to think about the question What is actually so hard about postponing aging? And the more I thought about it, the more I’d find I couldn’t really understand what was so hard.
So I started to talk about this to my wife and to other people of her generation, and it became apparent that they didn’t really know either, but that they regarded it as not an interesting problem, which was scandalous to me. I mean, I understand why they thought that, because, you see, scientists are interested in understanding things. They’re interested in knowledge for it’s own sake, whereas engineers are more interested in knowledge as a means to an end, and I think that I’m very much an engineer at heart.
So I was scandalized by this. Eventually, I was sufficiently scandalized that I went off and actually taught myself some of the relevant areas of biology that were not ones in which my wife herself was an expert–like biochemistry, for example–so as to be able to understand what was known about the biology of aging, and what people might actually try to do something about. I got very lucky. I was able to make an interesting contribution in one area of gerontology after I’d really only been reading the literature extensively for a month or two. That contribution was published and well-received in 1997. Since then I’ve basically been going without stopping.
David: Can you describe how you arrived upon your initial insight–your “aha” moment–of how the aging process can be reversed, and why you think that the key to longevity is basically an engineering problem?
Aubrey: I don’t think there was a real moment when I realized that it’s an engineering problem. It was obvious to me that it was an engineering problem. Bodies are just machines. They’re very complicated but they are just machines. The big breakthrough I made–that you may be referring to, and which has been talked about a little bit in other publications–is that in the summer of 2000 I realized something about how to approach the problem. This was not to approach the general concept of aging as an engineer, but actually how to break the problem down, how to subdivide it into parts that could each–with reasonable plausibility–be, not just slowed down, but actually repaired and reversed without too much risk of side-effects and things spinning out of control in ways that one couldn’t predict. That was in the middle of the night in Los Angeles in July of 2000.
David: What do you think are the seven primary causes of aging?
Aubrey: It’s probably not really quite correct to call them “the causes of aging.” What they are is the early manifestations of aging. These are intrinsic side-effects of metabolism, of being alive in the first place, and they are things that build up throughout life. Although these side-effects are not the cause of aging, they start to become harmful once they get to a certain level of abundance. Once there’s enough of them around the body starts to suffer from them and eventually it suffers seriously. But the point is that initially they are completely inert. So this is really why a twenty year old, and a thirty or forty year old, are more or less equivalent in terms of functionality–in as long they’ve looked after themselves reasonably well. You can run as fast, you can think as fast, and so on, more or less, because the things haven’t reached a pathogenic level.
So the seven areas are as follows. First of all, there is a loss of cells. There are certain tissues in which, when the cells in that tissue die the tissue doesn’t know how to replace them, not at the adequate rate anyway. For example, in the heart, or in certain areas of the brain, cells die and are not replaced.
The second one is the opposite of that. It’s having too many cells of a certain type. This includes cells that really ought to have