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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.
"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.
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