Scientists have discovered the genetic basis for a rare, fatal disorder that causes children to age before they grow up. The researchers say the work may provide insight into the normal aging process.
Most of us do not look forward to growing old, but a tiny number of children around the world, about one in every five million people, face that prospect decades sooner than the rest of us. They have a disease called progeria. It causes them to become shriveled, bald dwarfs as young children with health problems normally associated with the elderly. They suffer joint stiffness, hip dislocations, and frequently die of heart disease or stroke. The average age of death is thirteen.
John Tackett is a 15-year-old progeria patient from Bay City, Michigan who says his angina, a heart pain caused by poor blood oxygen supply, limits his physical activity.
"When I was younger, I used to go and play hockey and roller blade with the other kids and everything. That's something I really enjoy doing, but I can't anymore," he said.
There is no cure for progeria, but U.S. and French researchers working independently of each other have made a discovery that could lead to one. In separate papers in the journals "Science" and "Nature," they report finding the genetic mutation responsible for the disorder.
A defective progeria gene causes premature aging because it makes cells divide improperly and die prematurely. This flaw impairs the ability of tissue to renew itself.
Francis Collins led the U.S. team at the government's National Institutes of Health outside Washington. "This discovery has major consequences for diagnosis and potential new therapies for this devastating disease associated with premature aging," he said, "and it is likely to shed light on the normal process of aging and on heart attack and on stroke. Hence, it reverberates well beyond its applications specifically to progeria."
The studies were completed in record time. It took just one year for the U.S. researchers to locate the gene on chromosome one, one of 23 microscopic strings of DNA in our cells that contain all the information to build and maintain our bodies.
This speed is more impressive because this gene's mutation is so rare. Geneticist Ted Brown of the New York State Institute for Basic Research in Developmental Disabilities says the infrequency of the disorder makes it difficult to investigate.
"There have only been a handful of documented cases alive at any one time for a physician to study, so it has been a very difficult disease to get a handle on [to understand]," he said.
Making the research job harder is the fact that the disease is not passed down in families. Instead, says Dr. Brown, it results from a sporadic gene mutation in individuals.
"Such mutations are very difficult to find unless there is a family pattern of inheritance. There have been no clear biochemical markers that we've had to track the gene. So it's been a very difficult feature to study," he said.
Francis Collins says the research could not have succeeded so quickly just two or three years ago. He attributes the speed of the work to the success of the international human genome project, which he led. He announced recently that the project has been completed two years ahead of schedule. The result is a free public database on the Internet of the chemical sequence of virtually all human DNA, which shortens the work of scientists seeking genes.
"We've really crossed a bridge here in terms of the ability to do this kind of detection, and I think that bodes well for even more difficult problems that lie ahead us things like diabetes and mental illness, where we know that the finding of those genes is going to be quite a challenge because it is not just a gene, it's quite a few of them," he said.
With the progeria gene now uncovered, Dr. Collins says the U.S. National Institutes of Health has begun a study of people who have lived to be 100 to see if they have a protective version that delays aging.