Issue link: http://cp.revolio.com/i/393
18 #1 Fall 2008 ENGINEERING NEGLIGIBLE SENESCENCE Enter Dr. Aubrey de Grey, a biogerontologist from the UK, and his "strategies for engineered negligible senescence" (SENS) plan. Instead of exclusively studying the complex biochemical processes of aging in detail, as in gerontology, or ameliorating the worst symptoms of age-related decline, as in geriatrics, de Grey and his supporters advocate an "engineering approach" to aging that asks, what are the main categories of age-related biochemical damage, and how can we fix them? e idea is not to eliminate the sources of age-related damage, but to fix the damage fast enough so it doesn't accumulate and cause health problems. is is far easier than deciphering all the intricacies of the biochemistry of aging. Although some tentative engineering approaches to aging had been proposed be- fore, it was de Grey who really fleshed it out, popularized it, and made it respectable. It's no wonder that he has already raised $10 million in funding for his organization, the Methuselah Foundation. As de Grey points out, gerontologists have discovered seven biochemical causes of aging. e last cause was discovered in 1981, and considering how immensely far our knowledge of biology has come since that time, it seems quite likely that these seven causes are all of them. De Grey calls these causes of aging the "Seven Deadly ings." ey are: (1) cell loss, (2) death- resistant cells, (3) nuclear DNA mutations, (4) mitochondrial DNA mutations, (5) in- tracellular junk, (6) extracellular junk, and (7) extracellular crosslinks. at's it. If we find medicines or therapies that can clean up this damage, we could extend our lifes pans to great lengths and achieve negligible senescence in humans. A word on a philosophical point of view: many world philosophies and re- ligions teach, or strongly imply, that the body depends on some immaterial animat- ing force, a soul or chi, to give it life. Scien- tists disagree: the functioning of the body seems entirely rooted in atoms, molecules, and forces between them. As recently as 1907, French philosopher Henri Bergeson wrote about an élan vital, or vital force, that animated all living things and drove their evolution and development. is was close- ly connected to the idea, common at the time, that organic molecules could not be synthesized by inorganic precursors. Un- fortunately for Bergeson and other vitalists, Friedrich Wöhler, the father of biochem- istry, had already synthesized urea from inorganic precursors as early as 1828, and scientists were becoming more and more convinced that the same laws of biochemis- try that govern inorganic molecules govern organic molecules as well. Because the laws of chemistry apply to both life and non-life, aging is an entirely chemical, non-mystical process of degra- dation with specific physical causes. Al- though it is a matter of preference whether you consider aging a "disease" or not, from the perspective of the body, aging is like a disease -- a life-destroying biochemical phenomenon occurring in the body. And like diseases, aging is treatable. It is due to the complexity and the aura of inevitability around aging that people have only recently begun to look at it this way. Some say that aging is something mandated by God, and we have no right to mess with it, but these very same people have used this same argu- ment throughout history to protest against vaccinations, the dissection of cadavers, organ transplants, and numerous other therapies or techniques of extreme medi- cal value. Is it so radical to say that being healthy is a good thing, and that we should use whatever ethical strategies are available to pursue that end? Aubrey de Grey's SENS plan is com- plex and quite thorough. To examine it in full, I suggest looking at the website of the Methuselah Foundation, or getting his re- cent book, Ending Aging. But I will sum- marize the basics here. e first cause of aging is cell loss, or cell atrophy. For most of our lives, our bod- ies are programmed to replace cells when they die. Our individual cells live much shorter life spans than the body itself: some cells last a few years, others, like skin cells, a few weeks. All of them are constantly re- generated using the body's supply of stem cells. Over time, the processes of cell re- plenishment begin to break down. is is what causes muscle atrophy among the old, and the phenomenon especially afflicts the heart and brain, our two most important organs. To fix this problem, two strategies have been proposed: stimulating the divi- sion of existing cells, or introducing new cells, possibly including stem cells. Both are under investigation. e second cause of aging is death- resistant cells, cells that overstay their welcome. ere are three main types of cells guilty of this offense. e first are visceral fat cells, fat cells that build up around our internal organs. ese cause a progressive loss in our body's ability to respond to nutrients from the stomach. Eventually, it leads to Type 2 Diabetes. e second type of cells is called senescent cells, cells that have lost the ability to reproduce. ese stick around, releasing proteins that are dangerous to their neighbors. ankfully, they primarily aggregate in just one type of tissue, the cartilage between our joints. A third type is a category of immune cells called "memory cytotoxic T cells." ese build up faster than other immune cells and refuse to go away, crowding out the other immune cells and eventually causing disease. ere are two approaches to solving these problems: inject something that makes the unwanted cells commit suicide but doesn't touch other cells, or stimulate the immune system to kill the target cells. e third cause of aging is mutations in the DNA of the nucleus, the center of every cell. Most of these mutations are entirely harmless, as they only affect a few cells at a time. ese cells eventually die and are replaced with unmutated cells. Mutations get dangerous when they lead to malignant cells that self-replicate -- otherwise known as cancer. So, finding a cure for a cancer is a subtask of finding a cure for aging. Accord- ing to de Grey, this is the most difficult part of the strategy, because cancer is constantly evolving to exploit us. ere are several proposed approaches to finding a cure for cancer, but de Grey's favored strategy is one called "Whole-body Interdiction of Lengthening of Telomeres" (WILT). e Methuselah Foundation's website calls WILT "a very ambitious but potentially far more comprehensive and long-term approach to combating cancer We perish not because of some internal clock that says, "Time to die now!," but because of a lack of attention and self-healing mere neglect.