A book review of Aubrey de Grey’s Ending Aging
By: Eddie Germino
July 18th, 2008
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.
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.
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.
Ending Aging By: Aubrey de Grey. 400 pp. St. Martin’s Press. $26.95