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Week of 27 September 2002 · Vol. VI, No. 5
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Old age does not a prison make
Centenarians yield secrets of long life

By Hope Green

When Thomas Perls was a fellow in geriatrics, in 1993, he was surprised to find that his two eldest patients were among the healthiest he treated. Both were 100 years old.

 

Tom Perls directs the New England Centenarian Study. Photo by Gina DiGravio

 
 

"I had been brought up with this idea that the older you get, the sicker you get," Perls says. "These two centenarians went against the grain."

Perls, an associate professor at BU's School of Medicine, has since become an expert on "the oldest old," as he calls them, and is leading a hunt for the genetic secrets of longevity. He directs the New England Centenarian Study (NECS) at Boston Medical Center, the largest genetic study of centenarians in the world. By conducting interviews and analyzing genetic material from subjects, the researchers are seeking clues as to why some people age slowly and avoid diseases normally associated with aging, such as heart attacks, Alzheimer's disease, cancer, and stroke.

This work reflects a growing interest in elder health, at a time when the population is graying and 100th birthday parties are getting to be commonplace. The number of centenarians in the United States hovers around 50,000, three times as many as there were in 1980. Perls has found many of them to be surprisingly vigorous, mentally and physically. "Centenarians are raising the bar for what is possible for the rest of us," he says.

Perls founded NECS in 1994 at Harvard as a population-based study of all the centenarians in eight towns near Boston. Initial findings defied stereotypes: 90 percent of the subjects were functionally independent up until an average age of 92 years, and 75 percent were the same at an average age of 95 years.

A track record of healthful habits appears to pay off: obesity, and especially a history of smoking, is rare in the superannuated, according to results of Perls' survey. And a preliminary study led by his associate director at NECS, neuropsychologist Margery Silver, indicates that centenarians score low in a domain of personality testing called neuroticism -- meaning they tend to manage their emotions adeptly and cope well under stress.

But Perls also has produced evidence, contrary to conventional scientific thought, that a survival advantage runs in families. At least half the centenarians he initially studied had close relatives who achieved very old age. In a subsequent study, published last June, Perls and a demographer from UC-Berkeley, along with researchers from the Cambridge-based biotechnology firm Centagentix, Inc., analyzed data collected from 444 families that had at least one member living to age 100 or older. Brothers of centenarians were found to be 17 times more likely and sisters 8 times more likely to reach 100 than their counterparts in the general population.

In the laboratory, Perls is narrowing his search for what he refers to as a "genetic booster rocket" for longevity. Analyzing the genomes of 308 centenarians and their siblings, he and his research team found an area of genetic commonality on chromosome 4. Perls is now looking at that region of genes, somewhere between 50 and 500 in number, in hopes of finding a disease-resistant gene that siblings might share.

The discovery of a longevity-enabling gene and the exploration of its biochemical pathways, he says, could lead to the development of a drug that mimics the effects of the gene. The drug could be used to help older people stave off illness, or compress the duration of illness, toward the end of their lives.

Perls joined the MED faculty in February, along with Silver, an assistant professor, geriatrician Dellara Terry, an instructor, and several of their research assistants from Harvard. Terry is studying the children of centenarians, who have a markedly low risk of major diseases compared to others in their age cohort, particularly cardiovascular disease and diabetes.

Alzheimer's disease has long interested Perls, who is exploring its genetics and epidemiology in collaboration with Lindsay Farrer, a MED professor and chief of the genetics program. Silver, too, is conducting Alzheimer's research. Her neurological studies of centenarians support the theory that people can maintain their cognitive function for a remarkably long time, despite the presence of Alzheimer's-related changes in brain matter, if they make an effort to stay socially engaged and keep learning new things.

"This is caused by something called cognitive reserve," she says. "People who keep their brains challenged build up new connections between brain cells, which gives them a kind of buffer against Alzheimer's disease. And they seem to show symptoms later than people who haven't been as mentally active."

How we can improve the quality of our years is what counts most to Silver and Perls, coauthors of the internationally published Living to 100: Lessons in Living to Your Maximum Potential at Any Age (Basic Books, 1999).
"Certainly our intention is not to get a bunch of people to age 150," Perls says of the NECS team. "I don't think that's possible, and I think those who say it is are hucksters. Rather, if we could get people to be more centenarianlike, living a greater portion of their lives in good health, that would be terrific."

For more information about NECS, visit www.bumc.bu.edu/Departments/HomeMain.asp?DepartmentID=361.

       



27 September 2002
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