Issue link: https://cp.revolio.com/i/393
19 #1 Fall 2008 than anything currently available or in de- velopment." It is based on a vulnerability shared among all cancer cells: their need to renew their telomeres, junk DNA that serves as the ends of chromosomes. Telo- meres of a certain length are necessary for a cell to self-replicate. If the telomeres are too short, the cell self-destructs. When cancer hijacks the body's cells, the cancer cells replicate so rapidly that their telomeres shorten quickly. e cancer cells avoid destruction by using the cell's protein synthesis machinery to build enzymes -- telomerase and ALT -- that extend telomeres, and allow endless self- replication. Previous attempts at cancer cures target these enzymes, but WILT proposes removing the very genes that contain the information necessary to synthesize them. Removing the genes underlying the synthesis of telomerase will mean that all cancers will self-destruct before becom- ing a serious problem to their host, effec- tively curing cancer. is is one of the most ambitious strands of the SENS plan. e challenge of this approach is that removing these genes in all the tissues of the body will mean that the body's natural cells will have a limited life span, as they will not be capable of lengthening their telomeres. To counteract this will require introducing stem cells with renewed telomeres into the body every decade or so. is has already been demonstrated in mice with cells of the blood and gut. Skin and lungs will be next. When this therapy is used to cure cancer in mice, tremendous resources will be pumped into efforts to develop a therapy that works for humans. e fourth cause of aging is mutations in the mitochondria, the "power stations" of the cell. Mitochondria have their own DNA, much less than that in the nucleus of the cell, but some of it is essential to synthe- sizing the proteins that make it up. When the DNA is damaged, the mitochondria break down. Mitochondrial DNA is espe- cially susceptible to damage because of two reasons. e first is that mitochondria, be- ing the site of cellular respiration, are heav- ily exposed to its by-products -- dangerous free radicals. ese react with the DNA, causing it to mutate. e second is that mi- tochondria lack the complex DNA-repair machinery found in the nucleus. Luckily, although mitochondria are made of thousands of proteins, only 13 of them are synthesized using the genes of the mitochondria itself. e rest are synthesized in the nucleus and imported in. e solu- tion to this problem is to move the thirteen critical genes from the mitochondria to the nucleus of the cell. Evolution has already been doing this without our help for mil- lions of years, and we need to finish the job. is will require using gene therapy to add supplementary genes. Gene therapy is in its early stages, but has been used effectively to replace defective genes with functional ones, helping cure genetic diseases. Re- search is under way to improve the process and test it with mice. e fifth cause of aging is intracellular junk. Cells synthesize, reconstruct, and de- construct many thousands of different mol- ecules during the course of their operation. Every once in a while a cell ends up with a molecule so large or unusual that it has trouble breaking it up. If a molecule cannot be broken down by the "incinerator" of the cell, the lysosome, it stays there forever. In cells that don't divide, this can build up to critical levels. is includes some cells in the heart, the back of the eye, some nerve cells, and white blood cells trapped in the walls of arteries. is can cause diseases, such as Alzheimer's, Parkinson's, macular degener- ation (the leading cause of acquired blind- ness), and atherosclerosis. To clean up in- tracellular junk, the SENS project proposes equipping the lysosome with new enzymes, thereby expanding the range of molecules it can break down, allowing it to digest even very large or unusual molecules. e sixth cause of aging is extracellular crosslinks, molecular garbage that accumu- lates outside cells, linking together proteins that otherwise slide smoothly over each other. ese can lead to some of the most outwardly visible effects of aging: wrinkles in tissue and the like. Fortunately, these crosslink molecules have chemical struc- tures different than the healthy tissue of the body, so it shouldn't be too hard to find an enzyme that breaks them down while leaving the rest alone. In fact, just one type of crosslinks, called glucosepane crosslinks, may count for up to 98% of all long-lived extracellular crosslinks in the human body, meaning if we figure out a way to get rid of these, we'll have almost solved this cause of age-related damage. e seventh and last known cause of aging is general extracellular junk, the type that just floats around instead of linking together proteins. Most of these junk mol- ecules are called amyloids, and they build up in everyone, but are especially found in the brains of Alzheimer's patients. e main approach to dealing with this, already being pursued by at least one company, is to stimulate the body's immune cells to clear out these molecules. ere is a strong over- lap between treatments for Alzheimer's and atherosclerosis and anti-aging treatments that address this cause, so there seems to be significant momentum in the right di- rection. ere may be other causes of aging that emerge after we have solved most of these seven. We'll just have to wait and see. But if all these seven causes of aging were eliminated, people could live a lot longer -- maybe even hundreds of years. at would buy us more time to develop new therapies to address the remaining sources of aging. It's hard to imagine why we wouldn't want to fight the scourge of aging -- be- sides killing more than 100,000 people per day; it makes us suffer for years or decades before it kills us. Everyone is susceptible. Instead of seeing aging as inevitable, why don't we view it as a disease and search for a cure? Michael Anissimov is a science writer. He blogs at accelerating future. ...aging – besides killing more than 100,000 people per day; it makes us suffer for years or decades before it kills us. Resources Can Turtles Live Forever discovermagazine.com/2002/jun/featturtle Methusalah Foundation www.methusalahfoundation.com Anissimov Blog www.acceleratingfuture.com/michael/blog