Why We Die- A Press Release

[Guest guest]

This is a long press Release- I am a Republican, but am dismayed

at what our President and others have done to suppress Stem cell

Research.

Gene Found to Switch Off Stem Cells During Aging By NICHOLAS WADEBiologists have uncovered a deep link between lifespan and cancer in theform of a gene that switches off stem cells as a person ages. The critical gene, already well known for its role in suppressing tumors,seems to mediate a profound balance between life and death. It weighs thegeneration of new replacement cells, required for continued life, againstthe risk of death from cancer, which is the inevitable outcome of lettingcells divide. To offset the increasing risk of cancer as a person ages, thegene gradually reduces the ability of stem cells to proliferate.The new finding, reported by three groups of researchers online Wednesday in Nature, was made in a special breed of mice that lack the pivotal gene, butis thought likely to apply to people as well. The finding indicates that many of the degenerative diseases of aging arecaused by an active shutting down of the stem cells that renew the body'svarious tissues, and are not just a passive disintegration of tissues underlife's daily wear and tear, as is often assumed."I don't think aging is a random process - it's a program, an anti-cancerprogram," said Dr. Norman E. Sharpless of the University of North Carolina,senior author of one of the three reports. The two other senior authors areDr. J. on of the University of Michigan and Dr. T. Skaddenof the Harvard Medical School.The finding's implications for cell therapy based on using a patient's ownadult stem cells are not yet clear, but news that the cells get switched offwith age does not seem particularly encouraging. The result may undercutopponents of research with human embryonic stem cells who argue that adultstem cells are sufficient for cell therapy. Dr. Sharpless said his findingemphasized the need to pursue both types of research. The gene involved in the new finding has the unmemorable name of p16-Ink4abut plays a central role in the body's defenses against cancer. It producestwo quite different proteins that interact with the two principal systemsfor deciding whether a cell will be allowed to divide.One of these proteins had also been noted to increase substantially withage. The cells of a 70-year-old person produce 10 times as much of the Ink-4protein as do those of a 20 year-old, Dr. Sharpless said. To help understandwhy this was so, Dr. Sharpless genetically engineered a strain of mouse inwhich the gene was knocked out. He set out to see if loss of the gene would have any effect on the mice'sblood-making stem cells. Learning that Dr. on was interested in thesame question with brain cells, and Dr. Skadden with the insulin-makingcells of the pancreas, he shared his mice with them and the three teamsagreed to publish their findings together, a departure from the usualcompetitiveness between researchers.All three teams report essentially the same result, that in each type oftissue the cells have extra ability to proliferate when the Ink-4 proteincan no longer be made. At the same time the Ink-less mice are highly proneto cancer, which they start to develop as early as one year of age. The researchers assume, but have not yet proved, that the increasing amountsof Ink-4 made as a person ages will thrust the stem cells into senescence,meaning they can never divide again. The evolutionary purpose is evidentlyto avert the risk that a damaged stem cell might evade controls andproliferate into a tumor.One implication is that therapists hoping to increase longevity must tacklea system that may be hard to cheat. Any intervention that reduces productionof the Ink-4 protein in order to prevent the age-related decline of stemcells will also increase the risk of cancer."There is no free lunch - we are all doomed," Dr. Sharpless said. But hequickly modified his comment by noting that a calorically restricted diet isone intervention that is known to increase lifespan and reduce cancer, atleast in laboratory mice. The reason, he said, is probably because thesediets reduce cell division, the prime source of cancer risk. For celltherapists, the dual activity of Ink4 may be "a hard box to get out of," hesaid, unless they use cells that are somehow much younger than the patient.Dr. Skadden, however, said he hoped there would turn out to be somesloppiness in the Ink-4 gene's balancing trick, allowing it to be switchedoff temporarily with yet to be invented drugs in a way that would promotestem cell proliferation without greatly increasing the risk of cancer. "There is clearly a dark side to the finding, but whether or not we canexploit it, that's the challenge," he said.Some proposals for stem cell therapy with adult stem cells envisage taking apatient's stem cells, making them divide in the laboratory, and putting themback in the patient to build new tissue. "The notion that adult stem cellsare infinite in proliferative capacity is seriously undermined by thiswork," Dr. Sharpless said. Dr. on said it had long been known that older patients don't do aswell in bone marrow transplants as younger ones, and the new finding mightexplain why. "I don't think any of these findings dims the promise of stemcell research at all," he said, because the greater robustness of youngerpeople's cells was already well known.The researchers say they do not yet know what stimulus makes cells increasetheir production of the Ink-4 protein as a person grows older. Theirsuspicion is that the usual factors implicated in aging, such as mutationand oxidative damage to tissues, would turn out to play a role in makingcells produce more Ink-4. Dr. A. DePinho, an expert on cellular aging and a co-author of Dr.Skadden's report, said the new finding, in showing how the renewal capacityof stem cells was governed, might enable drugs to be made that would improve cell transplants.Dr. Lowe, a cancer gene expert at the Cold Spring Harbor Laboratorywho was not involved in the three papers, said the new results were veryinteresting because they linked to aging a gene of central importance incancer.Press releases issued by the University of North Carolina School of Medicineand the University of Michigan attributed the advance to all three teamsequally. But the press release issued by the Harvard Stem Cell Institute,where Dr. Skadden has an appointment, described him as the leader of themulti-institutional team, with the other two teams confirming his work. Dr.Skadden made no such claim in an interview, and acknowledged Dr. Sharpless'sgenerosity in lending his mice.

I wish you all the bestAubrey Pilgrim