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But even as Harley begins his search, other genes implicated in aging have already been flushed out of hiding. At McGill University, Hekimi's long-lived nematodes have helped expose a few of them. Hekimi created his little uberworms by crossing and recrossing individuals that lived longer naturally, slowly extending the life-spans of later generations. He then searched the animals' chromosomes until he found the mutated gene responsible, a gene he dubbed Clock-1. "The Clock-1 gene is critical in setting life-span," Hekimi says. "More important, with cloning and genetic mapping, we were able to determine just which protein the gene created to get that job done."
After locating three other nematode clock genes, Hekimi went looking for similar ones in people. He found one whose amino acid schematic nearly mirrored Clock-1's. "The Clock-1 genes in the two species are so very similar," he says, "that it's possible the whole clock system works the same way. If we find all of the human clock genes, we can perhaps slow them down just a little, so we can extend life."
In California, Michael Rose, who created the aged fruit flies, has not yet found the genes responsible for his insects' longevity, but does believe genetic manipulation can be a key to prolonging life. Manipulating any senescence genes could be years--indeed, decades--away. But the alternative--subjecting human beings to the same selective mating processes applied to lab animals--is out of the moral question. "We're not going to be breeding humans the way we breed fruit flies," he says. "We have to find some less fascistic method of intervening in aging."
Meanwhile, more and more genes involved in the aging process are giving up their secrets. At the Veterans Affairs Medical Center in Seattle, a group led by molecular geneticist Gerard Schellenberg has identified the human gene responsible for the disorder known as Werner's syndrome. People suffering from Werner's start life normally, but by the time they reach their 20s begin a process of eerily accelerated aging, exhibiting such ailments as heart disease, osteoporosis and atherosclerosis. Typically they die by their late 40s.
Schellenberg's work is noteworthy not only because he found the gene behind such misery, but because he knows how it works. The genetic sequence he discovered codes for the enzyme helicase, which is responsible for unzipping the DNA double helix before it replicates. If this unzipping is disrupted, helicase can't tweeze out mutations that randomly occur and instead allows them to pass through to the next cellular generation. Accumulate enough glitches, and diseases of aging develop. "We know that DNA is being damaged at a high rate," he says. "Knowing that a helicase is responsible gets us closer to solving the mystery."
If the mystery indeed is solved, the benefits could be enormous. Schellenberg suspects that the same helicase deficit that accelerates senescence in Werner's sufferers might, in a more measured form, cause aging in others. To prove this, he will create a strain of mouse that carries a mutant helicase gene so that he can learn how the enzyme works, and more important, how it can be manipulated. Depending upon what Schellenberg learns from these mice, it might be possible to sidestep genetics and simply use helicase boosters to slow aging in both Werner's patients and healthy people.