March 30, 2010
USA: Making Cells Live Forever in Quest for Cures
. NEW YORK, NY / Wall Street Journal / Health / March 30, 2010 By SHIRLEY S. WANG It's not quite the Fountain of Youth, but scientists have found a way to induce some of our cells to live forever. The purpose isn't to make people immortal, but rather to create therapies that might one day treat or delay the onset of disease, such as progressive eye disease, gastrointestinal disorders and cancer. The research is focused on so-called telomeres, small bits of DNA that serve as protective coverings at the end of our chromosomes. These caps keep our chromosomes from unraveling, much like the plastic tips at the ends of shoelaces. When our telomeres are healthy, our cells remain healthy. But each time the cells divide, telomeres get shorter. When they reach a critically short length, as they do with age or the onset of certain diseases, cells lose the ability to divide and eventually die. Three Americans discovered telomeres and the enzyme that makes them, called telomerase, in the 1980s, work for which they recently won the Nobel Prize in medicine. Since then, a growing number of researchers have been seeking to understand how telomeres work. One feat researchers have accomplished in the lab is using telomerase to "immortalize" human cells. Scientists from the University of Texas Southwestern Medical Center at Dallas and others have shown they can keep certain types of cells living forever, including those from the breast, skin, retina and, recently, the colon, by adding telomerase to keep telomeres intact or repair those that became too short. Now researchers are studying how telomerase-based therapies could help repair damaged cells and play an major role in cancer research. "What our goal should be isn't increasing life span, but healthy life span," says Jerry Shay who, with his UT Southwestern colleague Woodring Wright, first figured out how to use telomerase to immortalize cells in the late 1990s. "Is there some way we can intervene and slow down some of the problems?" Telomeres aren't the only reason we age, likely accounting for 10% or less of the aging process, biologists say. But if cells can be kept healthier longer, diseases that might have caused serious illness at 65 years old could be delayed until, say, 75. Compressing disease into a smaller window later in life could significantly improve individuals' quality of life, helping them live independently for longer rather than in a nursing home, says Dr. Shay, professor of cell biology and associate director of the Simmons Cancer Center at UT Southwestern. "Potentially we can keep you from getting too frail," he says. A limit to telomerase is that it benefits only cells that divide—and most neurons, the dominant type of cell in the brain, don't divide. If scientists could figure out a way to get telomerase even to the small portion of brain cells that do divide, there could be some brain benefit, according to Dr. Shay. A related concern is the possibility of inadvertently creating or accelerating cancer if telomerase were administered throughout the body, including to cancerous or pre-cancerous cells. Somehow, cancer cells have telomeres that are just the right length and don't shorten—a perfection of the division process that allows cells to keep dividing, Dr. Shay says. But if a telomerase-based therapy could be given to specific cells temporarily, say for a week or two, it could be a therapeutic "home run," repairing telomeres and allowing cells to keep dividing, Dr. Shay says. Such a therapy—which would actually occur on a patients' own cells grown in a lab dish—could help people with conditions where cells have been injured and have used up their allotment of telomeres, such as anemia or skin sores or conditions involving inflammation. Many cancer researchers are trying to figure out how to turn off telomerase and potentially treat cancer. More than a decade ago, Drs. Shay and Wright's team showed they could immortalize human retinal and foreskin cells by adding the gene for telomerase into a virus and then "infecting" the cells. Inside the cells, the virus began producing telomerase, and the cells kept growing and dividing indefinitely. These cells, still active today, are used by researchers all over the country to study cancer and other diseases. The Shay-Wright team published this work in Science in 1998. Since then, they have induced growth in epithelial cells, which are otherwise-normal, healthy cells from which cancer tends to develop. Previously, scientists had difficulty growing epithelial cells in a lab setting, which made studying cancer more difficult. Earlier this month, the Shay-Wright team published a paper in the journal Gastroenterology about immortalization of a line of epithelial colon cells, which can now be used to study colon cancer. Telomerase appears particularly to promote growth of cells that are descendents of stem cells. Embryonic stem cells, the focus of research in a number of diseases, are undifferentiated cells that can develop into highly specialized cells. Many efforts are under way to figure out how to reverse adult stem cells back to their embryonic state—called "induced pluripotent" stem cells—so that they may be used to repair damaged tissues. In experiments with lung cells, Drs. Shay and Wright are exploring how telomerase could be an alternative—and potentially easier—way of using stem cells to grow healthy tissue, without turning them all the way back to their embryonic state. "We age for multiple, multiple, multiple reasons," says Dr. Wright. Telomeres account for only a "small fraction" of the aging process, but if strides could be made to improve healthy life even by a little bit, "that's a huge amount," he says[rc] Shirley S. Wang E-Mail: firstname.lastname@example.org Copyright ©2010 Dow Jones & Company, Inc.