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Longevity researchers are looking for ways to extend not just years but vigor
The days of our years are threescore years and ten; and if by reason of strength they be fourscore years, yet is their strength labor and sorrow; for it is soon cut off, and we fly away. --Psalm 90.
If there were a pill that could add two decades to your life, would you swallow it? Not if you're like most people scientist Matt Kaeberlein asks--they see it as an invitation to purgatory. "Why would I want to be old for an extra 20 years?" they say. But when the
Researchers like Kaeberlein are learning that the aging process--not only how long we live but how well--is remarkably elastic and that it can be manipulated. The lives of lab animals have been dramatically stretched in several ways--by tweaking their genes, feeding them drugs, changing their diets--that seem to make them age more slowly while prolonging good health.
In theory, these strategies all do the same thing: fool the body into reacting as it would to a harsh environment, going into survival mode. The question is whether such techniques also can be made to work safely in humans.
Scientists like Cynthia Kenyon, a geneticist at the
The secret of slowing down human aging would be one of the greatest discoveries in medical history, says S. Jay Olshansky, a biodemographer at the
Hundreds of studies since the 1930s have shown that a below-normal intake of calories slows aging and greatly extends healthy life spans in organisms as simple as yeasts and as complex as rats. The journal Science recently reported that rhesus monkeys (our evolutionary cousins) whose daily calories were reduced 30 percent for 20 years had one third the risk, compared with normally fed monkeys, of developing age-related illnesses such as diabetes, cancer, heart disease, and brain deterioration. That suggests "quite convincingly" that their aging is being slowed, says Richard Weindruch, a professor of medicine at the
In another study, called CALERIE, researchers are investigating the effect of cutting calories by 25 percent for two years for people of roughly normal weight to see if they undergo the same sorts of changes seen in animals. There's reason for thinking they will, says John Holloszy, a professor of medicine at
There's also supporting evidence from an unintentional experiment. After eight people sealed themselves inside an Arizona biosphere in 1991, they were unable to grow enough food to support their arduous daily regimen and had to cut back from the planned 2,500 calories a day to about 2,000. At one point, their diet fell below 1,800 calories. They, too, seemed to undergo the beneficial bodily changes seen in animals on curtailed diets.
Still, we may never know whether calorie restriction can extend human longevity, says Holloszy. He can't imagine getting the government to fund a decades-long definitive study, and he'd have to wait an additional 40 years to see if the eldest Cronies rival Jeanne Louise Calment of France, whose 1997 death at age 122 made her the longest-lived person ever confirmed. "I won't be around then," says the 77-year-old Holloszy.
Even if restricting calories adds to life and improves health, following such a regimen is "almost impossible," says Holloszy. Constant hunger is common. Sex drive can slump. The body's thermostat can be thrown off--when everyone else is comfortable, the restricted-calorie crowd may pull out the long underwear. And men (women not as much, says Holloszy) often aren't pleased with the gaunt look. "I was so skinny that I elicited questions like 'Are you OK? Do you have cancer? Do you have AIDS?' " says
"What most people working in the area of caloric restriction hope is that once we understand how it works, we'll be able to produce the same effects by other methods," says Holloszy. "By taking a drug." If a pill was created that mimics the benefits of restricting calories, even Delaney admits that he would ditch the diet.
A few years ago, the happy prospect of a pill that would make the body behave as if it were being deprived of calories burst into the headlines when researchers reported that a compound found in the skin of red grapes called resveratrol, when fed to fat mice on a high-calorie diet, seemed to counteract the ill effects of their gluttony without their having to lift a paw. The mice stayed fat but compared with normally fed mice, they had better bones, heart function, and physical performance; fewer cataracts; and extra protection from diabetes. They also lived about 25 percent longer than overstuffed mice usually do. Resveratrol already was being sold as a supplement, and within weeks of the 2006 report in Nature, it was flying off the shelves even though there was no proof of the slightest benefit in people, says Rafael de Cabo, an investigator at the
Resveratrol's lasting legacy may turn out to be a better understanding of a family of enzymes called sirtuins. Both resveratrol and calorie restriction seem to act at least in part by activating these enzymes, which "regulate the body's defenses against aging and disease," says David Sinclair, a professor of pathology at
Last summer, scientists reported on another possible calorie-restriction mimetic. Three teams found that feeding older mice a drug called rapamycin, an immunosuppressant used to prevent organ rejection in transplant patients, significantly extended their lives, apparently by inhibiting an enzyme that is linked to the aging process. It was comparable to adding a robust decade to a human life span, says David Harrison, a professor at the
Don't expect to see an age-slowing drug approved soon, researchers say.
Clues from the very old
Living to 100 didn't get the warm reception Thomas Perls had expected when his book came out in 1999. He thinks the public assumed that anyone that old "must be in terrible shape." But Perls, who directs the New England Centenarian Study, has found that the vast majority of the centenarians in his sample are doing surprisingly well. Most are free of disabilities until the end of their lives--even those contending with significant age-related ailments, like heart disease. And the 1 out of 7 million people who reaches the "supercentenarian" age of 110 and beyond (there are 85 in his study) seems to dodge not only the effects of age-related conditions but the illnesses themselves. Or if these rare individuals do become ill at the end of their lengthy lives, they quickly die rather than languishing in declining health.
What's the secret of the oldest old? "Our hypothesis is that centenarians get to be 100 because they have some protection against age-related disease and maybe against aging," says Nir Barzilai, director of the
Both Barzilai and Perls are hunting for hints to healthy longevity in those who hit 100 to learn what it is about their genetic makeup that seems to help them along and whether that could help those of us with fewer genetic gifts. Nearly a quarter of Barzilai's 500 centenarians, for example, have a mutation that bestows on them levels of "good cholesterol" as high as triple normal concentration. He has found that those with the mutation also are largely immune from Alzheimer's disease and apparently have lower risk of heart disease, high blood pressure, and diabetes.
Even without miracle drugs, those of us who didn't "win the genetic lottery at birth," as Olshansky puts it, could add many years to our lives. "We are living about 10 years less than our potential -- mostly due to bad health behaviors," says Perls. Evidence comes from groups of similar individuals who do the right thing. Seventh-Day Adventists, for example, have an average life expectancy of about 88 years, the highest in the United States, he says. (The U.S. average is 78.) Adventists avoid red meat (many are vegetarian), exercise regularly, and don't drink alcohol or smoke. Their focus on religion and family may ease stress, itself a risk factor. "That's kind of the recipe," says Perls. It's one that doesn't rely on research breakthroughs, either. But even if a means to slow human aging and extend the healthy human life span eventually emerges from the laboratory, says Austad, "you could still get hit by a car, or your parachute doesn't open when you're sky diving." Science can't eliminate chance or bad luck.
David Sinclair, 40
Professor of pathology,
What he does: Has taken resveratrol, a compound found in the skin of red grapes, since 2003. He's even gotten his wife and parents to follow suit.
Why: Resveratrol may activate a family of longevity-related enzymes. Sinclair gave up a calorie-restricted diet, which may work similarly, after a week. "It just made life seem longer," he says.
Thomas Perls, 49
Director, New England Centenarian Study at
What he does: Tries to donate blood every eight weeks.
Why: Iron stimulates cells to churn out free radicals, molecules that may help cause cancer and other diseases of aging. Donating blood depletes some of the body's iron stores.
Mark Mattson, 52
What he does: Limits calories to 2,000 per day. Always skips breakfast and sometimes lunch. In addition to dinner, he grazes on fruits and veggies--and a bowl of oatmeal--during the evening.
Why: Research by Mattson and other scientists suggests that restricting calories (and occasional fasting) may benefit the brain and the body
Cynthia Kenyon, 55
What she does: Follows the low glycemic index diet, which limits high-carbohydrate foods (like pasta and bread) that the body quickly converts to sugar.
Why: To keep her blood sugar from spiking and triggering corresponding insulin surges. Insulin turns off a "longevity gene" Kenyon found in roundworms. An equivalent gene exists in people, and versions of it have been linked to long life.
Felipe Sierra, 56
Molecular biologist and director,
What he does: "I laugh a lot."
Why: "I really think that's the best we can do for a while," he says, amused by his own skeptical view of the status of aging research.
© U.S. News & World Report
Health - Aging - The Dawning of a Ripe Old Age