Starting to make SENS

Extended Mind — POSTED BY Cosmo on September 29, 2009 at 1:57 pm

A book review of Aubrey de Grey’s Ending Aging, by Eddie Germino

Dr. Aubrey de Grey is a man who hates seeing people suffer and die from old age. In fact, he has such contempt for it that he considers the aging process itself to be just another disease (albeit a very complex one) like AIDS or malaria…..

Dr. Aubrey de Grey is a man who hates seeing people suffer and die from old age. In fact, he has such contempt for it that he considers the aging process itself to be just another disease (albeit a very complex one) like AIDS or malaria. And like any other painful, terminal illness, he believes that aging should be cured for the sake of humanity. But perhaps most controversially, de Grey believes that aging can be cured, possibly soon enough to enable you to live for hundreds of years.

when someone like de Grey seriously suggests that science may provide a way to end aging and prolong life indefinitely, he unwittingly assaults deeply ingrained beliefs and is attacked in kind.

Of course, both the desirability and possibility of halting and then reversing human aging are polemical, and de Grey concedes that his are minority positions. But he nevertheless maintains that logic and science are on his side, and that his detractors are in a “pro-aging trance.” To explain, de Grey first cites the popularity of antiaging foods, supplements and plastic surgeries as proof that people clearly don’t like growing old. And why not? As he describes in luscious, scientific detail, aging entails slow degradation of mental and physical abilities, immune system strength, organ function, cellular-level health, and myriad other aspects of the body’s physiology, all of which reduce people to increasingly pitiful states until age-related failures finally kill them. People everywhere see the ravages of age and would rather not have it happen to them. But curiously, most of these same people will fanatically fight against de Grey’s proposals to develop antiaging medicines and treatments in a massive effort to eradicate aging as a cause of death. This disconnect stems from the fact that aging has been incurable for all of human history: Death from old age has always been an inescapable reality, and as such, people had to make peace with it by deeming it unavoidable, ennobling, and even necessary. These comforting yet illogical rationalizations constitute a “pro-aging trance,” and when someone like de Grey seriously suggests that science may provide a way to end aging and prolong life indefinitely, he unwittingly assaults deeply ingrained beliefs and is attacked in kind.

De Grey, who has a Ph.D from Cambridge and whose background as a former computer scientist gives him–as he claims–a unique engineer’s perspective on biology, notes with some bitterness that such prejudices exist even within scientific academia, which largely explains why his tentative cure for aging, called “Strategies for Engineered Negligible Senescence” (SENS), has not yet gained serious acceptance (though de Grey quickly notes that tacit and direct support for his ideas are growing among scientists). SENS consists of several highly advanced, theoretical medical treatments that could clean up the damage caused by the seven biochemical contributors to human aging. The seven factors, along with their corresponding SENS therapies, are as follows:

1) Mitochondrial DNA mutations lead to cellular-level overproduction of free radicals, which in turn travel throughout the body and cause damage to tissues by binding to them. This is fixed by transferring the mtDNA into the nuclei where it is better protected from damage and where it will be able to override the ill effects of mutated mitochondria.

2) Intracellular wastes (primarily lipofuscin) that humans cannot naturally destroy accumulate inside of the cells, physically impeding normal intracellular functions and overloading the lysosomes—the “waste disposal” organelles found in the cells. Solution: Identify these wastes, find enzymes that dissolve them, and then introduce the enzymes (modified so they will activate safely) into the body.

3) Damaged or malformed proteins floating around in the blood and cerebrospinal fluid aggregate into amyloid plaques that form “meshes” around cells and entire organs. The amyloid networks squeeze cells and can harden tissues. Correct the problem by developing vaccines against the amyloids so that the body’s immune system can be programmed to automatically attack and destroy plaques.

while SENS will eliminate aging, cancer, Alzheimer’s, and other common diseases as causes of suffering and death, de Grey is quick to point out that it will not deliver true immortality because it cannot protect against other misfortunes like homicides, fatal accidents or suicides. People will still die…just not for hundreds or thousands of years.

4) Sugars and fats consumed as food can, during the process of cellular digestion, bind to multiple cell proteins, crippling the latter by handcuffing them together. This causes tissues to gradually caramelize, harden and lose function. Develop drugs containing AGE-degrading enzymes to overcome the disease.

5) Permanent yet low-intensity viral infections like herpes and CMV put the immune system into perpetual overdrive. Some T-cells specialized to fight these diseases become defective and start “taking up space” at the expense of “naïve T-cells” which defend against all other pathogens. As a result, the body’s ability to fight common diseases like the flu is compromised since so many immune resources are devoted towards fighting the permanent infections. In response, develop drugs that make defective T-cells kill themselves, allowing the healthy T-cell population to expand. Also use stem cell therapy to rebuild the thymus, which is the organ that produces T-cells.

6) Cells (especially in the brain) are lost continuously as one ages, and this causes health problems. Use embryonic stem cell therapy to replace the lost cells and to repair various types of damage.

7) Nuclear DNA (nDNA) mutations accumulate with time. While most of these are harmless, mutations that activate the telomerase gene can be extremely dangerous by enabling uncontrolled reproduction. Moreover, cancer cells can only kill people if they can activate their own telomerase genes or if they harness the alternative lengthening of telomeres (ALT) pathway. Delete the telomerase genes and the ALT pathway from all somatic cells and then periodically replenish cell stocks with engineered stem cells.

However, “cure” is somewhat of a misnomer since SENS only repairs age-induced damage and does not neutralize the underlying human metabolic processes that cause the damage in the first place (de Grey finds human cell metabolism to be too finely balanced and complex to safely alter for antiaging purposes—a fact which he feels other biogerontologists miss). Concordantly, he envisions a not-too-distant future in which people periodically undergo rejuvenation treatments that eliminate all aging damage accumulated since the last SENS checkup. And while SENS will eliminate aging, cancer, Alzheimer’s, and other common diseases as causes of suffering and death, de Grey is quick to point out that it will not deliver true immortality because it cannot protect against other misfortunes like homicides, fatal accidents or suicides. People will still die…just not for hundreds or thousands of years.

Startlingly, de Grey thinks that such improvements to human longevity could happen by the end of this century, which would be soon enough to benefit adults alive right now. Advances in medicine will not only steadily increase lifespans over the coming decades, but will also improve the quality of life in old age and eventually provide means to slow, then halt, and finally reverse the aging process.

All of this, argues de Grey, should make the future success of SENS profoundly important to everyone. In his view, our lives literally depend upon us developing the necessary technologies and knowledge to implement the SENS therapies as soon as possible. To that end, de Grey again offers a strategy in the form of his “Methuselah Mouse Prize” or “MPrize” for short. The MPrize offers money ($4.5 million at last count) to the first scientist who accomplishes “robust mouse rejuventation” (RMR), which entails significantly increasing the lives of lab mice, with antiaging treatments starting in the mice’s middle age. Once RMR becomes a reality, de Grey believes that it will stand as a powerful proof of concept that human life could also be extended through similar means. Attitudes among both biogerontologists (people who study the aging process) and the general public will begin shifting as a result, and widespread pressure will force governments to begin pouring billions of dollars annually into SENS-related medical research. De Grey unsurprisingly ends the book with an appeal to the reader to donate to the MPrize.

Ending Aging is magnificent in that it ties together medical theory, the psychology of aging, and suggestions for present actions into an integrated whole. De Grey presents not only a fascinating program to defeat aging with SENS, but also bridges distant possibilities to the present via the MPrize. However, the book is not without its faults. While de Grey’s prose is at times highly engrossing, his expansive writing style wastes text (perhaps 30 pages all told) describing the irrelevant details of animal studies and the minutiae of his own thought processes. This reaches agonizing extremes in Chapter Nine’s discussions of new drug development, and one is left wondering how much better the book could have been given more editing.

De Grey’s attempt to simplify the details of SENS for average readers (Part II of Ending Aging) also falls short as his explanations remain too complex to appreciate without a college-level education in cell biology or some related field. The reader might therefore be forgiven for skipping over much of this section and instead focusing on de Grey’s simpler explanations of SENS found in Part I. What is clear from de Grey’s SENS manifesto is that his ideas and proposals are, by-and-large, extremely well researched, and there are no elementary flaws in his science or reasoning. One thus realizes that the only people capable of debunking the theory of SENS are other biogerontologists with Ph.D’s like de Grey, and in a noteworthy 2006 competition sponsored by MIT’s Technology Review, three separate teams of such scientists attempted to do just that, and failed.

Of course, this doesn’t mean de Grey’s plans for beating aging will necessarily work. For example, transferring mtDNA into cell nuclei might sound like a logical way to extend human lifespans, but actually doing it experimentally to test the idea will require a mastery of somatic genetic engineering—which is something several decades distant. De Grey also frequently fails to adequately discuss many other staggering technical hurdles that must be overcome to enable SENS therapies. It might therefore be a very long time before we can label SENS as good science or quackery. While Ending Aging remains an invaluable resource for understanding de Grey’s ideas, the reader must remember that they are still speculative and heavily criticized by mainstream scientists, and it would therefore be a mistake to finish the book thinking that the defeat of aging is a near-term prospect, or even one that is guaranteed to happen in our lifetimes. But determining SENS’ worth can only ever be done if we give it honest consideration, and with the stakes so high (100,000 people die daily from age-related diseases), the world would be remiss to ignore Aubrey de Grey.

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