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U. Wash. Scientists Identify Gene That Leads to Many of Aging's Symptoms

By Thomas H. Maugh II
Los Angeles Times

Scientists have identified a human gene that causes many of the symptoms of aging, providing researchers with their first peek into the complex and mysterious biochemical processes that produce the frailties of our twilight years.

Ironically, they found the gene in young people who suffer from a rare disorder called Werner's syndrome that produces premature aging. Victims not only turn gray and wrinkled while they are still young adults, but also suffer a vast array of age-related diseases, including arteriosclerosis, diabetes, cancer and osteoporosis.

The newly discovered gene is the blueprint for a protein called a helicase, Molecular biologist Gerard D. Schellenberg of the Seattle VA Medical Center and his colleagues at the University of Washington and Darwin Molecular Corp. report in Friday's edition of the journal Science.

Helicases unwind the well-known double helix of DNA so that individual strands can be repaired or replicated. DNA is constantly damaged by chemicals, radiation and viruses, and such repairs are an ongoing process to prevent the buildup of hazardous mutations.

A defect in the helicase, they speculate, causes Werner's disease by allowing the introduction of biochemical mutations during replication of cells.

"This is really exciting because it is the first time that any gene associated with aging has been identified," said molecular biologist David Finkelstein of the National Institute on Aging. "Werner's is not a perfect copy of the aging process," added Anna McCormick, chief of the institute's biology of aging branch, "but it's the best we have. This is important for what it can tell us about the involvement of DNA metabolism in normal aging."

Finding the gene has been "a kind of Holy Grail of aging research," Schellenberg said. In understanding how the gene works, he added, their goal is "not necessarily to arrest the aging process, but to help people age in a healthier way."

Because the defective gene appears to be so closely involved in triggering heart disease, cancer and osteoporosis, understanding how it works could lead to new treatments for those conditions, according to David J. Galas, chief scientific officer of Darwin. "We've got a full plate (of research) ahead of us, but it has really opened the door," he said.

Werner's strikes about three in every 1 million people worldwide, although it is slightly more common in the nation of Japan, the source of subjects for this study. "It's an extremely rare syndrome, so we are not going after the gene to cure Werner's," Galas said. We're really interested in what it will tell us about these other pathways" to cancer and heart disease.

The genetic disease is recessive, meaning that a child must inherit a defective copy from each parent to develop Werner's. As many as one in every 200 people may carry a single copy of the defective gene, Galas said, and this may predispose them to cancer and other diseases, even though they do not develop Werner's.

Victims of Werner's appear normal during their teens, but they begin to show dramatic differences from their contemporaries in their 20s. Their hair turns gray, and frequently they develop cataracts. As they continue to age prematurely, they develop other ailments of the aged - although they are remarkably free from high blood pressure and Alzheimer's - and usually die before the age of 50.