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Running parallel to Schellenberg's work is research being conducted at the New York State Institute for Basic Research into the more devastating Werner's-like disorder known as progeria. People suffering from progeria grow old precociously too, but at a much faster rate; they are claimed by the infirmities of age in their 20s or teens. W. Ted Brown, chairman of the Institute's Department of Human Genetics, believes that progeria, like Werner's, is triggered by a single mutated gene. That genetic miswiring, however, may stimulate activity in the countless other genes that play a role in aging. "Understanding all the genes," says Brown, "will help us understand aging in general."
The problem facing any scientist trying to find a genetic lever on the aging process is the sheer number of genes involved. Geneticist George Martin at the University of Washington in Seattle, who was involved in the discovery of the Werner's gene, believes that even if only a few master-clock genes directly guide aging in humans, up to 7,000 more might be peripherally involved. Re-engineering even one of these is an exquisitely complex process. Re-engineering all 7,000 would be impossible.
For the time being, therefore, many researchers are shifting their focus to goals that are more achievable. If the genes responsible for regulating senescence can't yet be manipulated, they wonder, is it possible to directly treat parts of the body they affect? Jerry Shay, a biologist specializing in cancer research at the University of Texas Southwestern Medical Center in Dallas, does not rule it out. Instead of engineering genes, he says, "we might be able to squirt some chemical to trigger telomerase at a particular site. The enzyme would turn on for a few weeks, change the expression of cells and revert them to a younger profile. We wouldn't have to treat the whole body."
Still other researchers are using what they've learned about telomeres and the other cellular mechanisms to attack the diseases that keep the very old from becoming still older. Researchers at Geron Pharmaceuticals recently published a study in which telomerase RNA was used to block the enzyme in a cancer culture, leading to withering of telomeres and the death of the no-longer-so-prolific cells. Elsewhere, investigators are looking into using the anticaramelization drug pimagedine to help clear arteries and improve cardiac health. Remove heart disease from the constellation of late-life illnesses, and you add three years to the national life expectancy. The detection of a gene that seems to confer protection against Alzheimer's disease may help treat yet another scourge of the aged, currently afflicting 4 million Americans.