Gene Study Seeks Secret of Long Life
Researchers believe they are closing in on the first human gene ever shown to increase longevity--a gene that might be able to add two decades to a healthy life span.
The researchers have been searching for the gene by analyzing DNA from families in which at least one sibling is 98 or older and another is in his or her 90s. They don’t know how the hypothetical gene would work, but because nearly all of the centenarians on which they have based their conclusions are quite healthy, they believe the gene might act to suppress or delay diseases associated with aging.
“We’re not trying to find the fountain of youth,” said Dr. Thomas Perls, one of the leaders of the research team based at Boston’s Beth Israel Deaconess Medical Center. “If anything, we are trying to find the fountain of aging well.”
“One thing you have to understand is the idea that you have to get sicker as you get older is not right,” Perls said. “If these people were getting age-associated diseases, they wouldn’t get to 100 in the first place. By and large, they are all very healthy.”
The research stems from a simple observation--many centenarians have elderly brothers and sisters. Indeed, that is one of the few similarities among people of advanced age, according to Perls, who has been studying centenarians since 1993.
Many of the families also have cousins and other relatives who are quite old.
“Many of the centenarians have eaten what they shouldn’t, some are obese and some smoke,” said Dr. Nir Barzilai of the Albert Einstein College of Medicine. “If there is anything unique about them, it is that they have survived despite their environment. . . . This is a great opportunity to find things that can override our environment.”
The research team believes that the elusive thing is a gene that their elderly subjects have that differs from the one possessed by most of the population. They have found that their subjects have a distinctive genetic marker on one small section of chromosome 4--one of the 23 chromosomes that make up the human genetic blueprint. That portion of the chromosome may contain 100 to 500 genes, and the research team is trying to home in on the right one.
The findings are published in today’s edition of the Proceedings of the National Academy of Sciences.
If a human longevity gene can be identified, scientists should be able to develop drugs to mimic its activity in people who are not blessed with it, enabling them to live longer lives as well.
“In the long run, we want to understand the aging process,” said Dr. Louis Kunkel of Children’s Hospital in Boston, whose team is conducting the DNA analysis. “These people are aging uniquely, and understanding how they do it is very important.”
Other researchers have previously identified longevity genes in fruit flies, worms and other organisms. While the researchers do not yet know the identity of the human gene they think they have nearly found, they do know that it is unlike those previous discoveries.
Experts cautioned that there is still a 5% possibility that the association between advanced age and the unique marker on chromosome 4 occurs simply by chance. “The discovery would be very exciting if it’s true, but I think it is too early to tell if it is going to be true,” said Dr. George Martin of the University of Washington. Martin noted that a similarly strong link of a gene to schizophrenia was subsequently shown to be a mistake.
Kunkel concedes the possibility that the results are wrong and that there may not be a longevity gene in the region.
“We wanted to get this study out because it really needs to be replicated by others,” he said. “We’ve made a hypothesis that there is a gene. Others need to test it or we need to prove it.”
Already, however, the research findings have generated excitement among scientists.
“It’s a very, very interesting lead,” said Richard Sprott, a behavioral geneticist and executive director of the Ellison Medical Foundation, which funds gerontological research. “Everybody will watch very closely to see what happens next”--whether the finding can be repeated in other centenarians.
Kunkel has already formed a company to look for the specific gene and has moved everyone who worked on the project in his laboratory to the company to accelerate the process. “We could have licensed [the discovery] to another company, but then we wouldn’t have had the fun of finding the gene,” he said.
Kunkel thinks they can narrow the search down to 100 genes or less within the next six months. “How fast we go after that will just depend on how lucky we get,” he added.
The subjects in the study are enrolled in the New England Centenarian Study, which is headed by Perls. The families have been collected from around the world. Perls’ team has so far identified 140 families in which there is a family member who is at least 98 and who has either a brother over the age of 91 or a sister over the age of 95. Surprisingly, the team found several families with three or four such siblings and one in which there are five.
Using those families, Kunkel’s team analyzed DNA from a total of 308 siblings ranging in age from 91 to 109, scanning across the entire genome to look for areas of similarity. Not all of the siblings had the genetic marker on chromosome 4--suggesting that there are other genes that may have a similar effect.
That’s not surprising, Kunkel said. He went into the study with the theory that there were perhaps four to six crucial genes for longevity.
Other scientists have predicted that there may be as many as 100 genes involved and have argued that finding them will be exceptionally difficult.
The new results “come out very strongly on one side of the controversy--that there are only a small number of genes associated with great longevity,” Sprott said.
To replicate the study and to locate the specific gene involved, the researchers need more subjects. Centenarians who think they might be eligible for the study should call (866) 548-3100.
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/ More information about the New England Centenarian Study is available at www.med.harvard.edu/programs/necs.
