Discoveries May Help Unlock Secrets of Long Life

Bijal P. Trivedi
National Geographic On Assignment
October 30, 2003
The ageless search for the secrets to long life has inspired recent
studies that overturn myths and offer promising clues.

In New York City, Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York, has led a study of more than 200 centenarians—Ashkenazi Jews—and their families, looking for potential "longevity genes" that may modify aging.

"When we asked people why they thought they lived so long, we got two answers," Barzilai said. "The first was that they had a mother who lived till 102 or a grandfather who lived till 108."

"The second answer was that they had 'something' protecting them. These were not people who exercised, they weren't vegetarians, some smoked heavily, some were very obese—but they could do anything and get away with it."

The protective "something" may be lipoproteins, Barzilai and his colleagues discovered. High- and low-density lipoproteins—the so-called "good" and "bad" cholesterols—both play a role in carrying fats throughout the body.

Among the centenarians, about 80 percent had lipoprotein molecules 30 percent larger than the control group. Barzilai's team also identified a form of gene that boosted the size of the lipoproteins in 26 percent of the long-lived group.

Large lipoproteins are associated with less cardiovascular disease, less hypertension, and reduced rates of metabolic syndrome.

A drug that increases the size of lipoproteins in the body might help prevent the onslaught of age-related diseases, Barzilai speculates in a study published in the October 15 issue of Journal of the American Medical Association.

Human Life Expectancy—Pushing the Envelope

"Barzilai's results are interesting but lipoproteins are just one factor among many," said Bernard Jeune, director of the Aging Research Center and of the Danish Centenarians Project at the University of Southern Denmark in Odense. "Reaching 100 is dependent on many factors."

Apparently longevity and good health don't always go together. "Some [centenarians] have delayed age-related diseases, some have escaped [them] but most have survived [them]," Jeune said.

Jeune's study has followed 300 people who reached their 100th birthday in 1995. Two of the remaining three died last week. "They were at opposite extremes," Jeune said. "The man had the fewest number of diseases in the entire study group; the woman, the most—she had 20 hospitalizations and six major operations."

Because centenarians are so different from one another, in health history and other ways, it's impossible to predict which 60, 70, and 80-year-old individuals will reach age 100, according to Jeune.

In the United States, the 2000 census counted about one centenarian per 5,578 people. In 1990 the figure was one in 6,667. But that slight rise can be misleading, said S. Jay Olshansky, a biodemographer at University of Illinois at Chicago.

"We are unlikely to extend life expectancy by several decades within any of our lifetimes," Olshansky said. "That sort of quantum leap is not going to happen unless we figure out a way to modify aging."

Life expectancy from birth in developed nations is now at about 77—75 for men and 80 for women. Olshansky envisions a peak of 85 (82 for men, 88 for women) at least for the next 80 years or so.

Stretching the Lifespan of Worms, Flies, Mice—And Humans?

Raising life expectancy to 85 is an enormous challenge, Olshansky pointed out. "You would have to reduce all death rates, from all causes, for all ages, by more than 55 percent," he said.

Between 1900 and 2000, life expectancy jumped about 30 years—a rise associated with saving the young. "We have used up the easy gains," Olshansky said.

To date, a "calorie restriction" diet is the only method that consistently prolongs the lives of mice, rats, dogs, flies, spiders, nematodes, paramecium, and yeast. Now researchers are investigating whether the same approach extends life in primates—in particular, humans. But the diet requires a 30 percent calorie reduction from what is considered a healthy diet—too heavy a price for most.

In labs around the world, researchers have doubled and tripled the lifespan of worms—and increased the lifespan of flies and mice by between 30 and 80 percent—by manipulating the activity of certain genes and hormones. (Many of the genes are also found in humans.)

Last week, in a lab at the University of California, San Francisco, researchers stretched the lifespan of C. elegans, a microscopic worm, by six-fold.

Ordinary worms live about 20 days. The mutant worms live on average about 124 days. "What is really extraordinary is that the long-lived mutant worms suffered no loss of health or vitality," said Cynthia Kenyon, a molecular biologist and professor biochemistry and biophysics at UCSF. The study was published in the October 24 issue of Science.

The lab produced a movie of worms actively wriggling at 144 days. "In human terms," Kenyon wrote, "these animals would correspond to healthy, active 500-year-olds."

"I think one day it will be possible to affect hormone pathways in humans to increase lifespan, by possibly 10 or 20 years, but it is hard to say when that will be possible," Kenyon said. "The experiments in worms, flies and mice show us where to begin.

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