19 October 2007

Book review: Ending Aging

Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime, by Aubrey de Grey, PhD, with Michael Rae.

Can the human aging process be stopped and even reversed, allowing the human lifespan to be extended indefinitely -- to centuries or even millennia? In this book, just published in September, Aubrey de Grey makes the case not only that is this possible, but that the necessary technology is much closer to being within our grasp than most would imagine.

De Grey is a biogerontologist who has been working for years on the problem of how exactly aging happens and how it can be defeated. He is also, it's worth pointing out, a very good writer; as you'll see below, the book necessarily deals with details of biology which are unfamliar to the average person and often dauntingly complex, but he succeeds in explaining them clearly so that any reasonably-well-educated reader can understand them. In places, the tale of the struggle to understand the processes at work in our bodies, and the hunt for solutions to problems, has the quality of a page-turning mystery story.

The aging process actually consists of several forms of damage which build up cumulatively in the body over decades, producing the well-known effects by which we recognize aging: declining memory and mental sharpness, weakening muscles, more fragile blood vessels, and so forth. De Grey argues that all this damage falls into just seven categories, and that if each of the seven kinds of damage could be prevented or repaired, the body would stop aging and in many respects even be restored to something close to the optimal functionality of early adulthood. His program for accomplishing this is called Strategies for Engineered Negligible Senescence (SENS).

Here are the seven categories of damage, and de Grey's proposed treatments:

Problem: Mutations in the DNA of the mitochondria (fuel-processing organelles within each cell), causing them to cease functioning; through a complex chain of effects, this causes damage to other cells throughout the organism.
Treatment: Insert back-up copies of the mitochondrial DNA into the cell nucleus, where they are much better protected from mutation and can keep the mitochondria functioning even if the original DNA is damaged. Inserting new genes into cell nuclei is a long-established technology; that's how genetic engineering of animals and plants is done. There are some technical problems with getting the mitochondrial DNA to work across the distance between the nucleus and the mitochondria, but de Grey discusses several promising strategies for overcoming these.

Problem: Formation of cross-links between protein molecules, a process known as "glycation", which causes loss of flexibility in the heart and blood vessels.
Treatment: Drugs which can break down these cross-links have already reached the stage of clinical trials on humans. So far their effects are limited, but the principles are well understood, and with enough investment more effective drugs should be possible.

Problem: Accumulation of chemical waste products inside cells. Our cells contain special bodies called lysosomes which break down and recycle most waste products, but there are a few types, collectively called "lipofuscin", which the lysosomes can't break down because they lack the necessary enzymes. These accumulate over decades, eventually crippling the cell.
Treatment: Use genetic engineering to give the lysosomes the enzymes they presently lack. The genes to produce these enzymes can be found in soil bacteria. (Why soil bacteria? Read the book -- it's fascinating.)

Problem: Accumulation of junk (mostly deformed protein molecules) between cells. The best-known and most serious example is the accumulation of beta-amyloid in the brain, which causes Alzheimer's disease.
Treatment: Use a vaccination-like technique to stimulate the immune system to attack and destroy the toxic substances, just as it normally attacks and destroys invading microorganisms. An Alzheimer's treatment using this technique has shown spectacular success in lab mice and is already in clinical trials with human subjects. Other forms of intercellular junk could be treated with other targeted "vaccines".

Problem: Toxic cells, that is, cells which in various ways damage or undermine the efficiency of the rest of the body.
Treatment: Various, depending on the type of cell. Some carry chemical markers which could enable them to be targeted for destruction by the immune system or by other techniques. Since these cells are involved in a number of major health problems, research on such treatments is already under way.

Problem: Cell depletion. Some types of cells do not divide, and are thus not replaced when they die. Thus the organs made up of these cells, notably the heart and brain, suffer cumulative cell loss over decades.
Treatment: Replace the dying cells using stem-cell therapy. There are several promising approaches already being worked on; one has already succeeded in restoring heart function in sheep after heart attacks, for example. The major obstacle here is not scientific but political (see below).

Problem: Mutations in the DNA of the cell nucleus. As de Grey argues at some length, these are not actually dangerous to the body except that they can turn cells cancerous. Given a long enough life, every person would eventually accumulate enough of these mutations to develop fatal cancer. Thus, in order to truly accomplish the goal of extending the lifespan indefinitely, this problem must be solved.
Treatment: Eliminate the gene for telomerase from the entire human system. Cells without telomerase can only divide a fixed number of times, then they stop. Any cell that turned cancerous would use up its fixed number of possible divisions long before it grew into a tumor large enough to be dangerous. Since there are several categories of cells which need to be able to divide an unlimited number of times in order to keep us healthy, the organs containing those cells would need to be replenished by stem-cell therapy at regular intervals (once a decade, roughly). I must say that this is the one aspect of de Grey's program which I found unconvincing. Eliminating telomerase -- something needed for normal bodily function -- is a much more radical modification of the human system than anything else de Grey proposes, and some of the regular cell replenishments to compensate for this would involve major, invasive surgery. Fortunately, even if de Grey's proposal is impractical, it does not invalidate the overall premise of SENS. Cancer research is already one of the best-funded areas of medical science, and much progress has already been made (de Grey notes that the NCI has set the goal of eliminating death and suffering from cancer by 2015, though he thinks it unlikely that this can be achieved). By various approaches we will continue to make progress against cancer and eventually eradicate it.

In every case, de Grey's proposed treatment is based on well-established current knowledge; in most cases, the treatment he describes or something quite similar is actually already being developed or even at the animal or human testing stage, even if the intent of the work is to address some more specific problem than combating aging in general. Of course, even when the full SENS program is available for use on humans, it will not work perfectly, but it won't have to; extending the vigorous lifespan by even a few decades would allow people to benefit from further refinements and new technology which would be developed during those decades, thus extending their lives still further, and so on.

How long will this take? De Grey is very cautious, but estimates that there is at least a 50% chance that the full SENS program of treatments could be ready for use in humans 25 to 30 years from now; under the best-case scenario it could be as soon as 15 years. Also, treatments for some of the seven forms of damage will become available sooner than others, and each step forward will also lengthen our maximum potential lifespan to some degree, improving the odds that any given individual will live long enough to benefit from the next breakthrough, and so on. And I tend to think that advances in other areas, such as computer modeling, will enable progress to move somewhat faster than he anticipates.

It's important to mention that de Grey is not claiming that SENS can make people immortal. Even if aging is totally eradicated, other causes of death such as disease, accidents, murder, and war will still exist. But there will no longer be a fixed upper limit on how long a person who avoids all these threats can live.

(Other thinkers such as Ray Kurzweil anticipate that innovations outside the field of biology, such as nanotechnology and brain uploading, will eventually achieve something very close to real immortality. Such possibilities are outside the purview of de Grey's book, however.)

The main obstacle to achieving SENS is not technological feasibility but money. The costs involved will be enormous. Only national governments can provide funding on the necessary scale, which they will not do until politicians, and the public on whom they depend for votes, can overcome the reflexive tendency to dismiss the whole idea as implausible. The only way to prove to the mass public mind that SENS is feasible is to actually achieve at least a limited version of it in the laboratory; to stimulate efforts to this end, de Grey has created the Methuselah Mouse Prize, a research prize for achieving a precisely-defined degree of lifespan extension in lab mice; you can read about it here. The book also discusses ways that individuals can contribute to research -- on this, see also de Grey's website. Once clear-cut rejuvenation and lifespan extension are achieved in mice, de Grey believes, the public will understand that the same can be done in humans, and will press governments to provide the necessary funding.

(The book does not try to address the various common objections made by people who think that eradicating aging would actually be a bad thing; on that issue, see de Grey's FAQ here, and also the links under "Objections Answered" in the left sidebar here.)

There is also the maddeningly-unnecessary political obstacle I mentioned, which is the Bush administration's restrictions on embryonic stem-cell research, a subject about which de Grey is scathing. While biological research goes on in many countries, the United States is still by far the biggest contributor, and the fact that stem-cell research in the US has been crippled for years has slowed down overall progress worldwide. Not only are there the restrictions on funding, but fundamentalist Republicans have introduced bills which, incredibly, would actually provide jail terms for scientists working with embryonic stem cells, and even penalties for Americans who traveled to other countries to obtain stem-cell therapies banned in the US (p. 264). Luckily, these bills failed to pass. De Grey also addresses the common right-wing claim that equally-good results can be achieved with adult stem cells as with embryonic stem cells, and explains exactly why this is far from true.

Embryonic stem cells have already been used to cure animal models of multiple sclerosis, cerebral palsy, stroke, Parkinson's disease, macular degeneration, and several other diseases (pp. 247-248). If it were not for the administration's policy, cures for those affliction in humans might be already available or very close. As it is, they are probably still several years away. Foreign countries and some individual US states have continued to fund research, but progress will really take off only when we have an administration which does not subjugate science to primitive religious taboos.

There is, of course, far more to this book than can be discussed in a short review. My main response while reading it was a growing sense of hopefulness and confidence that human ingenuity can, in fact, accomplish what de Grey says it can. Read the book and see for yourself.

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4 Comments:

Blogger Chell said...

You probably know where I stand on all this. Yet this is really interesting. Curiousity- guess it does the opposite of what we thought. While the seven solutions sound pretty sci-fi (to a non-scientist, earthy sort), I'm curious about whether or not such a unified "solution" will ever be fully developed. I mean, all of the single steps figured out. And then, I wonder if most people will fully turn to the "solution," or just a few of those steps, perhaps steps they've already taken without thinking much about it.

19 October, 2007 12:06  
Blogger Infidel753 said...

Chell, thanks for your comment. I know how radical some of this must sound. I fully admit I'm not an expert, but I think I do know substantially more about biology than the average person (due to a long-standing interest in the subject). With the exception of my reservations about the cancer/telomerase issue, I'm pretty much convinced that the treatments de Grey describes are feasible in the near future. Remember, in most cases the same or similar treatments are already being employed for more limited uses, or are under development.

As for people who object to life extension, they will certainly always have the right to refuse new treatments, just as adults today (such as Christian Scientists) are free to refuse whatever current medical procedures they object to on whatever grounds. The only pro-death people I have a problem with are the ones who want to stop or slow down progress in this field, and deny such treatments to those of us who want them.

19 October, 2007 13:30  
Anonymous Blurber said...

This sounds very promising. Pity it's too late for us old-timers who cells are already aged.

24 October, 2007 09:27  
Blogger Infidel753 said...

Actually, according to de Grey, the effect of most of these treatments would actually be to reverse the effects of aging to at least some extent, not just stop the process from going further. For anyone who would have a reasonable expectation of still being alive for another decade, there's grounds for optimism. The crucial variable is really how fast the research can move ahead.

24 October, 2007 21:07  

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