Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetimeby Aubrey de Grey, Michael Rae
With a New Afterword
Must We Age?
Nearly all scientists who study the biology of aging agree that we will someday be able to substantially slow down the aging process, extending our productive, youthful lives. Dr. Aubrey de Grey is perhaps the most bullish of all such researchers. As has been reported in media outlets/b>/b>/b>/b>/b>
With a New Afterword
Must We Age?
Nearly all scientists who study the biology of aging agree that we will someday be able to substantially slow down the aging process, extending our productive, youthful lives. Dr. Aubrey de Grey is perhaps the most bullish of all such researchers. As has been reported in media outlets ranging from 60 Minutes to The New York Times, Dr. de Grey believes that the key biomedical technology required to eliminate aging-derived debilitation and death entirelytechnology that would not only slow but periodically reverse age-related physiological decay, leaving us biologically young into an indefinite futureis now within reach.
In Ending Aging, Dr. de Grey and his research assistant Michael Rae describe the details of this biotechnology. They explain that the aging of the human body, just like the aging of man-made machines, results from an accumulation of various types of damage. As with man-made machines, this damage can periodically be repaired, leading to indefinite extension of the machine's fully functional lifetime, just as is routinely done with classic cars. We already know what types of damage accumulate in the human body, and we are moving rapidly toward the comprehensive development of technologies to remove that -damage. By demystifying aging and its postponement for the nonspecialist reader, de Grey and Rae systematically dismantle the fatalist presumption that aging will forever defeat the efforts of medical science.
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The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime
By Aubrey de Grey, Michael Rae
St. Martin's PressCopyright © 2007 Aubrey de Grey
All rights reserved.
It was 4 a.m. in California, but my body insisted on reminding me that it was noon in Cambridge. I was exhausted from the intercontinental flight and by a day spent in debate with some of the most influential personalities in biogerontology, at an invitation-only brainstorming workshop on ideas to combat aging. Evolutionary biologist Michael Rose was there. So were calorie restriction researchers Richard Weindruch and George Roth, nanotechnologist Robert Freitas, and several others. But I couldn’t sleep: On top of the mismatch between biological and geographical clocks, I was frustrated at what I saw as the day’s failure to make any real progress toward a concrete, realistic anti-aging plan. As I dozed and pondered, a question on the nature of metabolism and aging wormed its way into my brain and wouldn’t let go.
In my bleary irritation, I sat up, ran my hands over my beard, and began pacing the room, turning over the quandary in my mind. “Normal” metabolism was just so messy, and the raging debates in the biogerontology literature showed how difficult it was to determine what paced what: which metabolic disruptions were causes of aging, and which were effects (or secondary causes) that would simply disappear if the underlying primary causes were addressed. How could we make a positive difference in such a complex, poorly understood system? How could any meaningful change made in metabolism not be like a butterfly flapping its wings—apt to cause large, unwanted storms further down the line?
Then a second line of thought began to form in my mind—idly at first, just as a notion. The real issue, surely, was not which metabolic processes cause aging damage in the body, but the damage itself. Forty-year-olds have fewer healthy years to look forward to than twenty-year-olds because of differences in their molecular and cellular composition, not because of the mechanisms that gave rise to those differences. How far could I narrow down the field of candidate causes of aging by focusing on the molecular damage itself?
Well, I thought, it can’t hurt to make a list . . .
There are mutations in our chromosomes, of course, which cause cancer. There is glycation, the warping of proteins by glucose. There are the various kinds of junk that accumulate outside the cell (“extracellular aggregates”): beta-amyloid, the lesser-known transthyretin, and possibly other substances of the same general sort. There is also the unwholesome goo that builds up within the cell (“intracellular aggregates”), such as lipofuscin. There’s cellular senescence, the “aging” of individual cells, which puts them into a state of arrested growth and causes them to produce chemical signals dangerous to their neighbors. And there’s the depletion of the stem cell pools essential to healing and maintenance of tissue.
And of course, there are mitochondrial mutations, which seem to disrupt cellular biochemistry by increasing oxidative stress. I had for a few years felt optimistic that scientists could solve this problem by copying mitochondrial DNA from its vulnerable spot at “ground zero,” within the free-radical generating mitochondria, into the bomb shelter of the cell nucleus, where damage to DNA is vastly rarer.
Now, if only we had solutions like that for all of this other stuff, I mused, we could forget about the “butterfly effect” of interfering with basic metabolic processes, and just take the damage ITSELF out of the picture.
Well, I thought, why the bloody hell not?
I went back over my list. Protein glycation? A biotech startup was already running clinical trials using a drug that had been shown to break the dysfunctional handcuffing of the proteins that this process caused. The extracellular aggregates? Here again, animal studies had shown that you could just remove the damage, in this case by vaccinating against the amyloid plaque and letting immune cells gobble the stuff up. In theory, at least, there were all kinds of ways to deal with cellular senescence, though I wasn’t sure which of them would ultimately pan out. Anyone who’d read a newspaper in the last year knew that scientists were hotly pursuing a way to deal with the loss of cells: stem cells, cultured in the lab and delivered as a rejuvenating cellular therapy. Lipofuscin? It was at this point in my survey that I began to feel I might really be on to something, because just a year previously I’d come up with a way to eliminate lipofuscin that, although extremely novel, had already secured the enthusiastic interest of a few of the top researchers in that area. I didn’t have any radical new ideas up my sleeve for cancer; it was going to have to rely (for now, at least) on other people’s ideas. But that was okay: after all, there was already a huge effort under way to deal with it. And as for other problems arising from nuclear mutations, I had recently come to the admittedly counterintuitive conclusion that they were not in fact a major cause of age-related cellular dysfunction.
I went over my list again and again, and as I did so I became ever surer that there was no clear-cut exception. The combination of my own idea for eliminating intracellular garbage like lipofuscin; the idea I’d been championing for a few years for making mitochondrial mutations harmless; and the various other therapies being worked on by others around the world for addressing glycation, amyloid accumulation, cell loss, senescent cells and cancer—it seemed that this was really and truly an adequately exhaustive list. Not necessarily totally exhaustive—there certainly might be other things going wrong in the body—but very possibly comprehensive enough to give a few decades of extra life to people who are already in middle age before we start the treatments. And that was certainly a much more promising first step than anything that had been suggested the previous day, or in the many conferences and articles that I’d devoured over the previous few years.
For decades, my colleagues and I had been earnestly investigating aging in the same way that historians might “investigate” World War I: as an almost hopelessly complex historical tragedy about which everyone could theorize and argue, but about which nothing could fundamentally be done. Perhaps inhibited by the deeply ingrained belief that aging was “natural” and “inevitable,” biogerontologists had set themselves apart from the rest of the biomedical community by allowing themselves to be overawed by the complexity of the phenomenon that they were observing.
That night, I swept aside all that complexity, revealing a new simplicity in a complete redefinition of the problem. To intervene in aging, I realized, didn’t require a complete understanding of all the myriad interacting processes that contribute to aging damage. To design therapies, all you have to understand is aging damage itself: the molecular and cellular lesions that impair the structure and function of the body’s tissues. Once I realized that simple truth, it became clear that we are far closer to real solutions to treating aging as a biomedical problem, amenable to therapy and healing, than it might otherwise seem.
Grabbing a notepad, I jotted down the molecular and cellular changes that I could confidently list as important targets for the new class of anti-aging therapies that I would soon call SENS, the “Strategies for Engineered Negligible Senescence.” Each of them accumulated with age in the body throughout life and contributed to its pathological decay at later ages. As far as I could tell, the list was exhaustive, but I’d present it to my colleagues and see if they could add to it. I rushed downstairs before breakfast to transcribe my scrawled notes onto a flipchart in the meeting room. I was bursting to present my new synthesis to my esteemed colleagues. But truth be told, I already knew full well that at this first hearing they’d greet it with blank stares. The paradigm shift was just too great. Copyright © 2007 by Aubrey de Grey. All rights reserved.
Excerpted from Ending Aging by Aubrey de Grey, Michael Rae. Copyright © 2007 Aubrey de Grey. Excerpted by permission of St. Martin's Press.
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Meet the Author
Aubrey de Grey, Ph.D., is chairman and chief science officer of the Methuselah Foundation, and editor-in-chief of Rejuvenation Research, the only peer-reviewed academic journal focusing on intervention in aging. He has formulated a wide-ranging plan for the comprehensive and eventually indefinite postponement of age-related physical and mental decline, named SENS (Strategies for Engineered Negligible Senescence). He is the organizer of an ongoing series of conferences and workshops that focus on the key biomedical research relevant to SENS, and he also oversees the Methuselah Foundation's growing sponsorship of SENS research worldwide.
Michael Rae is Dr. de Grey's research assistant. He is a longtime member and onetime board member of the Calorie Restriction Society, a main contributor to the society's "How-to Guide," and a core scientific investigator with the society's Cohort Study, which seeks to document the feasibility of calorie restriction in humans and the potential human translatability of the anti-aging effects observed in laboratory organisms.
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I am not a scientist nor qualified to make an accurate evaluation of the ideas presented in this book. However, de Grey's ideas on ending aging are very interesting and make logical sense when thinking about the big picture of aging. He makes a very compelling argument throughout this book on the different ways to eliminate "junk" in our bodies and restore our body's systems to a youthful state. I am concerned, however, with some of his ideas. As stated in the previous review, I am also concerned with his ideas for treating cancer. Eliminating male fertility to me would be a grave concern for most males needing cancer treatment and would be met with great resistance. However, he did state in an earlier part of his book that he would rather wait for others to come up with a solution for cancer. I think that is his best option in that matter. Another concern of mine is that he approaches some of his ideas too scientifically and doesn't account for the "human" factor. In the end, I think most of his ideas will lead to a revolution in the way the world thinks about aging. His work, along with the work of his colleagues in other fields, will help lead us into the age of agelessness.
This book reviews ways to reverse the aging damage in our bodies. I am not an expert and so cannot comment on whether this book is accurate or authoritative. However, I really hope that someone finds ways to do what de Grey suggests. The book's science is extremely interesting, and, at least to a layman, the book is well worth reading for that alone. I have a couple of regrets about this book, however. One is that the method de Grey suggests for ending the threat of cancer, would also end male fertility forever. De Grey doesn't seem to mind this. I sure would, however. My second regret is that throughout the book, de Grey comes across as a con artist or snake oil salesman. I know that the journal Nature bothered to review this book; I believe de Grey is telling the truth when he says he has been a scientist. But I don't know what to think about his fundamental honesty and reliability. I would hesitate greatly before sending money to his Methuselah foundation, even though I dearly want aging cured as soon as possible.
Dr. de Grey's book is a compelling call to research and implementation of medical techniques that can potentially lengthen life and improve quality through those years. Although he considers the aspects of aging he addresses comprehensive (and they are each important), he neglects the grosser aspects of aging: arthritic deformities, loss of teeth, skin changes, organ distortion and enlargement and hormonal changes. It is nevertheless an important and exciting treatment of the frontier of age management medicine.