ROANOKE TIMES
Copyright (c) 1996, Roanoke Times
DATE: Friday, April 12, 1996 TAG: 9604120078
SECTION: NATIONAL/INTERNATIONAL PAGE: A-1 EDITION: METRO
DATELINE: WASHINGTON
SOURCE: Associated Press
A GENE THAT CAUSES premature aging has started a search for the keys to more normal infirmities of the elderly.
Scientists have taken the first step toward unlocking genetic mysteries of aging, discovering a gene that one day might lead to treatments for - or even slowing of - diseases that hit the elderly.
The gene causes Werner's syndrome, which turns 20-year-olds' hair gray and gives them ailments more common to their grandparents. Unraveling this premature aging should help doctors better understand normal aging.
``A kind of Holy Grail of aging research has been to find this gene,'' said Gerard Schellenberg, whose team at the Seattle Veterans Affairs Medical Center won an international race to identify the gene named WRN.
The gene appears to play a vital role in how DNA repairs itself and reproduces, long suspected as keys to aging, Schellenberg reports in today's edition of the journal Science.
``This is the first clear evidence'' to explain how that could happen, said Dr. Anna McCormick, chief of aging research at the National Institutes of Health.
This is all early research - treatments for aging are a long way off, and certainly many still undiscovered genes are involved, Schellenberg and other scientists agree.
Nor does WRN offer gene therapy for Werner's, because every copy of the gene in every cell is defective, a problem too massive to fix, McCormick cautioned.
But the discovery does offer ``a whole new window into age-related diseases,'' said David Galas, chief scientist for Darwin Molecular Corp., a Seattle biotechnology company that holds the patent rights to the gene. The company hopes the discovery will point the way to future drugs.
Werner's syndrome is a rare, inherited disease. Victims' hair turns gray in their 20s. Soon, cataracts cloud their vision and osteoporosis, heart disease, cancer and other ailments hit. Most victims die before age 50.
Doctors consider Werner's a model for research on normal aging.
Werner's is slightly more common in Japan, and a rival gene-hunter at Osaka University shared with Schellenberg his patients' tissue samples. Schellenberg then teamed with Darwin Molecular to sequence one of the largest DNA batches ever screened in a gene hunt - 650,000 bases, or chemical units.
Normal WRN appears to govern the production of vital enzymes called helicases, Schellenberg reported.
DNA carries the body's genetic blueprint, in double-helix strands coiled inside every cell. Whenever a cell reproduces, the DNA strands first must uncoil so they can be copied accurately for the new cell. Likewise, whenever the body needs to repair a cellular defect, the DNA must unwind so repair enzymes can snip off the defective piece. Helicases make DNA unwind.
``Whatever you can imagine that happens to DNA, helicases are involved,'' Schellenberg said.
If WRN is mutated, presumably the helicases aren't uncoiling DNA properly - so cells aren't reproducing to replace dying ones or DNA damage is not being repaired, Schellenberg explained.
His next step is to prove that is what's happening, by examining the four WRN mutations he found in Werner's patients. When he checked the WRN genes of 144 healthy people, only one had a mutation on a single copy of the gene. Both copies must be defective for Werner's syndrome to develop.
NIH's McCormick also wants to check the WRN of healthy people at different times in their lives to see if the gene's activity changes with normal aging.
Darwin Molecular is lining up test patients to see how WRN links various diseases.
``The exciting thing about this is it shows an error in DNA metabolism which actually connects cancer with cardiovascular disease,'' because Werner's causes both, Galas said. ``It's the first gene that's ever really made that connection.''
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