Louis
10-30-2006, 06:24 PM
From the NYT web site:
One for the Ages: A Prescription That May Extend Life
By MICHAEL MASON
How depressing, how utterly unjust, to be the one in your social circle who is aging least gracefully.
In a laboratory at the Wisconsin National Primate Research Center, Matthias is learning about time’s caprice the hard way. At 28, getting on for a rhesus monkey, Matthias is losing his hair, lugging a paunch and getting a face full of wrinkles.
Yet in the cage next to his, gleefully hooting at strangers, one of Matthias’s lab mates, Rudy, is the picture of monkey vitality, although he is slightly older. Thin and feisty, Rudy stops grooming his smooth coat just long enough to pirouette toward a proffered piece of fruit.
Tempted with the same treat, Matthias rises wearily and extends a frail hand. “You can really see the difference,” said Dr. Ricki Colman, an associate scientist at the center who cares for the animals.
What a visitor cannot see may be even more interesting. As a result of a simple lifestyle intervention, Rudy and primates like him seem poised to live very long, very vital lives.
This approach, called calorie restriction, involves eating about 30 percent fewer calories than normal while still getting adequate amounts of vitamins, minerals and other nutrients. Aside from direct genetic manipulation, calorie restriction is the only strategy known to extend life consistently in a variety of animal species.
How this drastic diet affects the body has been the subject of intense research. Recently, the effort has begun to bear fruit, producing a steady stream of studies indicating that the rate of aging is plastic, not fixed, and that it can be manipulated.
In the last year, calorie-restricted diets have been shown in various animals to affect molecular pathways likely to be involved in the progression of Alzheimer’s disease, diabetes, heart disease, Parkinson’s disease and cancer. Earlier this year, researchers studying dietary effects on humans went so far as to claim that calorie restriction may be more effective than exercise at preventing age-related diseases.
Monkeys like Rudy seem to be proving the thesis. Recent tests show that the animals on restricted diets, including Canto and Eeyore, two other rhesus monkeys at the primate research center, are in indisputably better health as they near old age than Matthias and other normally fed lab mates like Owen and Johann. The average lifespan for laboratory monkeys is 27.
The findings cast doubt on long-held scientific and cultural beliefs regarding the inevitability of the body’s decline. They also suggest that other interventions, which include new drugs, may retard aging even if the diet itself should prove ineffective in humans. One leading candidate, a newly synthesized form of resveratrol — an antioxidant present in large amounts in red wine — is already being tested in patients. It may eventually be the first of a new class of anti-aging drugs. Extrapolating from recent animal findings, Dr. Richard A. Miller, a pathologist at the University of Michigan, estimated that a pill mimicking the effects of calorie restriction might increase human life span to about 112 healthy years, with the occasional senior living until 140, though some experts view that projection as overly optimistic.
According to a report by the Rand Corporation, such a drug would be among the most cost-effective breakthroughs possible in medicine, providing Americans more healthy years at less expense (an estimated $8,800 a year) than new cancer vaccines or stroke treatments.
“The effects are global, so calorie restriction has the potential to help us identify anti-aging mechanisms throughout the body,” said Richard Weindruch, a gerontologist at the University of Wisconsin who directs research on the monkeys.
Many scientists regard the study of life extension, once just a reliable plotline in science fiction, as a national priority. The number of Americans 65 and older will double in the next 25 years to about 72 million, according to government census data. By then, seniors will account for nearly 20 percent of the population, up from just 12 percent in 2003.
Earlier this year, four prominent gerontologists, among them Dr. Miller, published a paper calling for the government to spend $3 billion annually in pursuit of a modest goal: delaying the onset of age-related diseases by seven years.
Doing so, the authors asserted, would lay the foundation for a healthier and wealthier country, a so-called longevity dividend.
“The demographic wave entering their 60s is enormous, and that is likely to greatly increase the prevalence of diseases like diabetes and heart disease,” said Dr. S. Jay Olshansky, an epidemiologist at the University of Illinois at Chicago, and one of the paper’s authors. “The simplest way to positively affect them all is to slow down aging.”
Science, of course, is still a long way from doing anything of the sort. Aging is a complicated phenomenon, the intersection of an array of biological processes set in motion by genetics, lifestyle, even evolution itself.
Still, in laboratories around the world, scientists are becoming adept at breeding animal Methuselahs, extraordinarily long lived and healthy worms, fish, mice and flies.
In 1935, Dr. Clive McCay, a nutritionist at Cornell University, discovered that mice that were fed 30 percent fewer calories lived about 40 percent longer than their free-grazing laboratory mates. The dieting mice were also more physically active and far less prone to the diseases of advanced age.
Dr. McCay’s experiment has been successfully duplicated in a variety of species. In almost every instance, the subjects on low-calorie diets have proven to be not just longer lived, but also more resistant to age-related ailments.
“In mice, calorie restriction doesn’t just extend life span,” said Leonard P. Guarente, professor of biology at the Massachusetts Institute of Technology. “It mitigates many diseases of aging: cancer, cardiovascular disease, neurodegenerative disease. The gain is just enormous.”
For years, scientists financed by the National Institute on Aging have closely monitored rhesus monkeys on restricted and normal-calorie diets. At the University of Wisconsin, where 50 animals survive from the original group of 76, the differences are just now becoming apparent in the older animals.
Those on normal diets, like Matthias, are beginning to show signs of advancing age similar to those seen in humans. Three of them, for instance, have developed diabetes, and a fourth has died of the disease. Five have died of cancer.
But Rudy and his colleagues on low-calorie meal plans are faring better. None have diabetes, and only three have died of cancer. It is too early to know if they will outlive their lab mates, but the dieters here and at the other labs also have lower blood pressure and lower blood levels of certain dangerous fats, glucose and insulin.
“The preliminary indicators are that we’re looking at a robust life extension in the restricted animals,” Dr. Weindruch said.
Despite widespread scientific enthusiasm, the evidence that calorie restriction works in humans is indirect at best. The practice was popularized in diet books by Dr. Roy Walford, a legendary pathologist at the University of California, Los Angeles, who spent much of the last 30 years of his life following a calorie-restricted regimen. He died of Lou Gehrig’s disease in 2004 at 79.
Largely as a result of his advocacy, several thousand people are now on calorie-restricted diets in the United States, says Brian M. Delaney, president of the Calorie Restriction Society.
Mike Linksvayer, a 36-year-old chief technology officer at a San Francisco nonprofit group, embarked on just such a diet six years ago. On an average day, he eats an apple or some cereal for breakfast, followed by a small vegan dish at lunch. Dinner is whatever his wife has cooked, excluding bread, rice, sugar and whatever else Mr. Linksvayer deems unhealthy (this often includes the entrée). On weekends, he occasionally fasts.
Mr. Linksvayer, 6 feet tall and 135 pounds, estimated that he gets by on about 2,000 to 2,100 calories a day, a low number for men of his age and activity level, and his blood pressure is a remarkably low 112 over 63. He said he has never been in better health.
“I don’t really get sick,” he said. “Mostly I do the diet to be healthier, but if it helps me live longer, hey, I’ll take that, too.”
continued on next post
One for the Ages: A Prescription That May Extend Life
By MICHAEL MASON
How depressing, how utterly unjust, to be the one in your social circle who is aging least gracefully.
In a laboratory at the Wisconsin National Primate Research Center, Matthias is learning about time’s caprice the hard way. At 28, getting on for a rhesus monkey, Matthias is losing his hair, lugging a paunch and getting a face full of wrinkles.
Yet in the cage next to his, gleefully hooting at strangers, one of Matthias’s lab mates, Rudy, is the picture of monkey vitality, although he is slightly older. Thin and feisty, Rudy stops grooming his smooth coat just long enough to pirouette toward a proffered piece of fruit.
Tempted with the same treat, Matthias rises wearily and extends a frail hand. “You can really see the difference,” said Dr. Ricki Colman, an associate scientist at the center who cares for the animals.
What a visitor cannot see may be even more interesting. As a result of a simple lifestyle intervention, Rudy and primates like him seem poised to live very long, very vital lives.
This approach, called calorie restriction, involves eating about 30 percent fewer calories than normal while still getting adequate amounts of vitamins, minerals and other nutrients. Aside from direct genetic manipulation, calorie restriction is the only strategy known to extend life consistently in a variety of animal species.
How this drastic diet affects the body has been the subject of intense research. Recently, the effort has begun to bear fruit, producing a steady stream of studies indicating that the rate of aging is plastic, not fixed, and that it can be manipulated.
In the last year, calorie-restricted diets have been shown in various animals to affect molecular pathways likely to be involved in the progression of Alzheimer’s disease, diabetes, heart disease, Parkinson’s disease and cancer. Earlier this year, researchers studying dietary effects on humans went so far as to claim that calorie restriction may be more effective than exercise at preventing age-related diseases.
Monkeys like Rudy seem to be proving the thesis. Recent tests show that the animals on restricted diets, including Canto and Eeyore, two other rhesus monkeys at the primate research center, are in indisputably better health as they near old age than Matthias and other normally fed lab mates like Owen and Johann. The average lifespan for laboratory monkeys is 27.
The findings cast doubt on long-held scientific and cultural beliefs regarding the inevitability of the body’s decline. They also suggest that other interventions, which include new drugs, may retard aging even if the diet itself should prove ineffective in humans. One leading candidate, a newly synthesized form of resveratrol — an antioxidant present in large amounts in red wine — is already being tested in patients. It may eventually be the first of a new class of anti-aging drugs. Extrapolating from recent animal findings, Dr. Richard A. Miller, a pathologist at the University of Michigan, estimated that a pill mimicking the effects of calorie restriction might increase human life span to about 112 healthy years, with the occasional senior living until 140, though some experts view that projection as overly optimistic.
According to a report by the Rand Corporation, such a drug would be among the most cost-effective breakthroughs possible in medicine, providing Americans more healthy years at less expense (an estimated $8,800 a year) than new cancer vaccines or stroke treatments.
“The effects are global, so calorie restriction has the potential to help us identify anti-aging mechanisms throughout the body,” said Richard Weindruch, a gerontologist at the University of Wisconsin who directs research on the monkeys.
Many scientists regard the study of life extension, once just a reliable plotline in science fiction, as a national priority. The number of Americans 65 and older will double in the next 25 years to about 72 million, according to government census data. By then, seniors will account for nearly 20 percent of the population, up from just 12 percent in 2003.
Earlier this year, four prominent gerontologists, among them Dr. Miller, published a paper calling for the government to spend $3 billion annually in pursuit of a modest goal: delaying the onset of age-related diseases by seven years.
Doing so, the authors asserted, would lay the foundation for a healthier and wealthier country, a so-called longevity dividend.
“The demographic wave entering their 60s is enormous, and that is likely to greatly increase the prevalence of diseases like diabetes and heart disease,” said Dr. S. Jay Olshansky, an epidemiologist at the University of Illinois at Chicago, and one of the paper’s authors. “The simplest way to positively affect them all is to slow down aging.”
Science, of course, is still a long way from doing anything of the sort. Aging is a complicated phenomenon, the intersection of an array of biological processes set in motion by genetics, lifestyle, even evolution itself.
Still, in laboratories around the world, scientists are becoming adept at breeding animal Methuselahs, extraordinarily long lived and healthy worms, fish, mice and flies.
In 1935, Dr. Clive McCay, a nutritionist at Cornell University, discovered that mice that were fed 30 percent fewer calories lived about 40 percent longer than their free-grazing laboratory mates. The dieting mice were also more physically active and far less prone to the diseases of advanced age.
Dr. McCay’s experiment has been successfully duplicated in a variety of species. In almost every instance, the subjects on low-calorie diets have proven to be not just longer lived, but also more resistant to age-related ailments.
“In mice, calorie restriction doesn’t just extend life span,” said Leonard P. Guarente, professor of biology at the Massachusetts Institute of Technology. “It mitigates many diseases of aging: cancer, cardiovascular disease, neurodegenerative disease. The gain is just enormous.”
For years, scientists financed by the National Institute on Aging have closely monitored rhesus monkeys on restricted and normal-calorie diets. At the University of Wisconsin, where 50 animals survive from the original group of 76, the differences are just now becoming apparent in the older animals.
Those on normal diets, like Matthias, are beginning to show signs of advancing age similar to those seen in humans. Three of them, for instance, have developed diabetes, and a fourth has died of the disease. Five have died of cancer.
But Rudy and his colleagues on low-calorie meal plans are faring better. None have diabetes, and only three have died of cancer. It is too early to know if they will outlive their lab mates, but the dieters here and at the other labs also have lower blood pressure and lower blood levels of certain dangerous fats, glucose and insulin.
“The preliminary indicators are that we’re looking at a robust life extension in the restricted animals,” Dr. Weindruch said.
Despite widespread scientific enthusiasm, the evidence that calorie restriction works in humans is indirect at best. The practice was popularized in diet books by Dr. Roy Walford, a legendary pathologist at the University of California, Los Angeles, who spent much of the last 30 years of his life following a calorie-restricted regimen. He died of Lou Gehrig’s disease in 2004 at 79.
Largely as a result of his advocacy, several thousand people are now on calorie-restricted diets in the United States, says Brian M. Delaney, president of the Calorie Restriction Society.
Mike Linksvayer, a 36-year-old chief technology officer at a San Francisco nonprofit group, embarked on just such a diet six years ago. On an average day, he eats an apple or some cereal for breakfast, followed by a small vegan dish at lunch. Dinner is whatever his wife has cooked, excluding bread, rice, sugar and whatever else Mr. Linksvayer deems unhealthy (this often includes the entrée). On weekends, he occasionally fasts.
Mr. Linksvayer, 6 feet tall and 135 pounds, estimated that he gets by on about 2,000 to 2,100 calories a day, a low number for men of his age and activity level, and his blood pressure is a remarkably low 112 over 63. He said he has never been in better health.
“I don’t really get sick,” he said. “Mostly I do the diet to be healthier, but if it helps me live longer, hey, I’ll take that, too.”
continued on next post