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Part 1
Read the text and answer questions 1–13.
The Search for the Anti-aging Pill
In government laboratories and elsewhere, scientists are seeking a drug able to prolong life and youthful vigor. Studies of caloric restriction are showing the way
A
As researchers on aging noted recently, no treatment on the market today has been proved to slow human aging - the build-up of molecular and cellular damage that increases vulnerability to infirmity as we grow older.
But one intervention, consumption of a low-calorie* yet nutritionally balanced diet, works incredibly well in a broad range of animals, increasing longevity and prolonging good health.
Those findings suggest that caloric restriction could delay aging and increase longevity in humans, too.
B Unfortunately, for maximum benefit, people would probably have to reduce their caloric intake by roughly thirty per cent, equivalent to dropping from 2,500 calories a day to 1,750. Few mortals could stick to that harsh a regimen, especially for years on end. But what if someone could create a pill that mimicked the physiological effects of eating less without actually forcing people to eat less? Could such a ‘caloric-restriction mimetic', as we call it, enable people to stay healthy longer, postponing age-related disorders (such as diabetes, arteriosclerosis, heart disease and cancer) until very late in life? Scientists first posed this question in the mid-1990s, after researchers came upon a chemical agent that in rodents seemed to reproduce many of caloric restriction's benefits. No compound that would safely achieve the same feat in people has been found yet, but the search has been informative and has fanned hope that caloric-restriction (CR)mimetics can indeed be developed eventually. The benefits of caloric restriction.
C The hunt for CR mimetics grew out of a desire to better understand caloric restriction's many effects on the body. Scientists first recognized the value of the practice more than 60 years ago, when they found that rats fed a low-calorie diet lived longer on average than free-feeding rats and also had a reduced incidence of conditions that become increasingly common in old age. What is more, some of the treated animals survived longer than the oldest-living animals in the control group, which means that the maximum lifespan (the oldest attainable age), not merely the normal lifespan, increased. Various interventions, such as infection-fighting drugs, can increase a population's average survival time, but only approaches that slow the body's rate of aging will increase the maximum lifespan.
D The rat findings have been replicated many times and extended to creatures ranging from yeast to fruit flies, worms, fish, spiders, mice and hamsters. Until fairly recently, the studies were limited to short-lived creatures genetically distant from humans. But caloric-restriction projects underway in two species more closely related to humans - rhesus and squirrel monkeys - have made scientists optimistic that CR mimetics could help people.
E The monkey projects demonstrate that, compared with control animals that eat normally, caloric-restricted monkeys have lower body temperatures and levels of the pancreatic hormone insulin, and they retain more youthful levels of certain hormones that tend to fall with age.
F The caloric-restricted animals also look better on indicators of risk for age-related diseases. For example, they have lower blood pressure and triglyceride levels (signifying a decreased likelihood of heart disease), and they have more normal blood glucose levels (pointing to a reduced risk for diabetes, which is marked by unusually high blood glucose levels). Further, it has recently been shown that rhesus monkeys kept on caloric-restricted diets for an extended time (nearly 15 years) have less chronic disease. They and the other monkeys must be followed still longer, however, to know whether low-calorie intake can increase both average and maximum lifespans in monkeys. Unlike the multitude of elixirs being touted as the latest anti-aging cure, CR mimetics would alter fundamental processes that underlie aging. We aim to develop compounds that fool cells into activating maintenance and repair. How a prototype caloric-restriction mimetic works.
G The best-studied candidate for a caloric-restriction mimetic, 2DG (2-deoxy-D-glucose), works by interfering with the way cells process glucose. It has proved toxic at some doses in animals and so cannot be used in humans. But it has demonstrated that chemicals can replicate the effects of caloric restriction; the trick is finding the right one.
H Cells use the glucose from food to generate ATP (adenosine triphosphate), the molecule that powers many activities in the body. By limiting food intake, caloric restriction minimizes the amount of glucose entering cells and decreases ATP generation. When 2DG is administered to animals that eat normally, glucose reaches cells in abundance but the drug prevents most of it from being processed and thus reduces ATP synthesis. Researchers have proposed several explanations for why interruption of glucose processing and ATP production might retard aging. One possibility relates to the ATP-making machinery's emission of free radicals, which are thought to contribute to aging and to such age-related diseases as cancer by damaging cells. Reduced operation of the machinery should limit their production and thereby constrain the damage. Another hypothesis suggests that decreased processing of glucose could indicate to cells that food is scarce (even if it isn't) and induce them to shift into an anti-aging mode that emphasizes preservation of the organism over such ‘luxuries' as growth and reproduction. * calorie: a measure of the energy value of food.
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B Unfortunately, for maximum benefit, people would probably have to reduce their caloric intake by roughly thirty per cent, equivalent to dropping from 2,500 calories a day to 1,750. Few mortals could stick to that harsh a regimen, especially for years on end. But what if someone could create a pill that mimicked the physiological effects of eating less without actually forcing people to eat less? Could such a ‘caloric-restriction mimetic', as we call it, enable people to stay healthy longer, postponing age-related disorders (such as diabetes, arteriosclerosis, heart disease and cancer) until very late in life? Scientists first posed this question in the mid-1990s, after researchers came upon a chemical agent that in rodents seemed to reproduce many of caloric restriction's benefits. No compound that would safely achieve the same feat in people has been found yet, but the search has been informative and has fanned hope that caloric-restriction (CR)mimetics can indeed be developed eventually. The benefits of caloric restriction.
C The hunt for CR mimetics grew out of a desire to better understand caloric restriction's many effects on the body. Scientists first recognized the value of the practice more than 60 years ago, when they found that rats fed a low-calorie diet lived longer on average than free-feeding rats and also had a reduced incidence of conditions that become increasingly common in old age. What is more, some of the treated animals survived longer than the oldest-living animals in the control group, which means that the maximum lifespan (the oldest attainable age), not merely the normal lifespan, increased. Various interventions, such as infection-fighting drugs, can increase a population's average survival time, but only approaches that slow the body's rate of aging will increase the maximum lifespan.
D The rat findings have been replicated many times and extended to creatures ranging from yeast to fruit flies, worms, fish, spiders, mice and hamsters. Until fairly recently, the studies were limited to short-lived creatures genetically distant from humans. But caloric-restriction projects underway in two species more closely related to humans - rhesus and squirrel monkeys - have made scientists optimistic that CR mimetics could help people.
E The monkey projects demonstrate that, compared with control animals that eat normally, caloric-restricted monkeys have lower body temperatures and levels of the pancreatic hormone insulin, and they retain more youthful levels of certain hormones that tend to fall with age.
F The caloric-restricted animals also look better on indicators of risk for age-related diseases. For example, they have lower blood pressure and triglyceride levels (signifying a decreased likelihood of heart disease), and they have more normal blood glucose levels (pointing to a reduced risk for diabetes, which is marked by unusually high blood glucose levels). Further, it has recently been shown that rhesus monkeys kept on caloric-restricted diets for an extended time (nearly 15 years) have less chronic disease. They and the other monkeys must be followed still longer, however, to know whether low-calorie intake can increase both average and maximum lifespans in monkeys. Unlike the multitude of elixirs being touted as the latest anti-aging cure, CR mimetics would alter fundamental processes that underlie aging. We aim to develop compounds that fool cells into activating maintenance and repair. How a prototype caloric-restriction mimetic works.
G The best-studied candidate for a caloric-restriction mimetic, 2DG (2-deoxy-D-glucose), works by interfering with the way cells process glucose. It has proved toxic at some doses in animals and so cannot be used in humans. But it has demonstrated that chemicals can replicate the effects of caloric restriction; the trick is finding the right one.
H Cells use the glucose from food to generate ATP (adenosine triphosphate), the molecule that powers many activities in the body. By limiting food intake, caloric restriction minimizes the amount of glucose entering cells and decreases ATP generation. When 2DG is administered to animals that eat normally, glucose reaches cells in abundance but the drug prevents most of it from being processed and thus reduces ATP synthesis. Researchers have proposed several explanations for why interruption of glucose processing and ATP production might retard aging. One possibility relates to the ATP-making machinery's emission of free radicals, which are thought to contribute to aging and to such age-related diseases as cancer by damaging cells. Reduced operation of the machinery should limit their production and thereby constrain the damage. Another hypothesis suggests that decreased processing of glucose could indicate to cells that food is scarce (even if it isn't) and induce them to shift into an anti-aging mode that emphasizes preservation of the organism over such ‘luxuries' as growth and reproduction. * calorie: a measure of the energy value of food.
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Part 2
Read the text and answer questions 14–27.
GREYING POPULATION STAYS IN THE PINK
A
Elderly people are growing healthier, happier and more independent, say American scientists.
The results of a 14-year study to be announced later this month reveal that the diseases associated with old age are afflicting fewer and fewer people and when they do strike, it is much later in life.
B In the last 14 years, the National Long-term Health Care Survey has gathered data on the health and lifestyles of more than 20,000 men and women over 65. Researchers, now analysing the results of data gathered in 1994, say arthritis, high blood pressure and circulation problems - the major medical complaints in this age group - are troubling a smaller proportion every year. And the data confirms that the rate at which these diseases are declining continues to accelerate. Other diseases of old age - dementia, stroke, arteriosclerosis and emphysema - are also troubling fewer and fewer people.
C 'It really raises the question of what should be considered normal ageing,' says Kenneth Manton, a demographer from Duke University in North Carolina. He says the problems doctors accepted as normal in a 65-year-old in 1982 are often not appearing until people are 70 or 75.
D Clearly, certain diseases are beating a retreat in the face of medical advances. But there may be other contributing factors. Improvements in childhood nutrition in the first quarter of the twentieth century, for example, gave today's elderly people a better start in life than their predecessors.
E On the downside, the data also reveals failures in public health that have caused surges in some illnesses. An increase in some cancers and bronchitis may reflect changing smoking habits and poorer air quality, say the researchers. These may be subtle influences,' says Manton, 'but our subjects have been exposed to worse and worse pollution for over 60 years.It's not surprising we see some effect'.
F One interesting correlation Manton uncovered is that better-educated people are likely to live longer. For example, 65-year-old women with fewer than eight years of schooling are expected, on average, to live to 82. Those who continued their education live an extra seven years. Although some of this can be attributed to a higher income, Manton believes it is mainly because educated people seek more medical attention.
G The survey also assessed how independent people over 65 were, and again found a striking trend. Almost 80% of those in the 1994 survey could complete everyday activities ranging from eating and dressing unaided to complex tasks such as cooking and managing their finances. That represents a significant drop in the number of disabled old people in the population. If the trends apparent in the United States 14 years ago had continued, researchers calculate there would be an additional one million disabled elderly people in today's population. According to Manton, slowing the trend has saved the United States government's Medicare system more than $200 billion, suggesting that the greying of America's population may prove less of a financial burden than expected.
H The increasing self-reliance of many elderly people is probably linked to a massive increase in the use of simple home medical aids. For instance, the use of raised toilet seats has more than doubled since the start of the study, and the use of bath seats has grown by more than 50%. These developments also bring some health benefits, according to a report from the MacArthur Foundation's research group on successful ageing. The group found that those elderly people who were able to retain a sense of independence were more likely to stay healthy in old age.
I Maintaining a level of daily physical activity may help mental functioning, says Carl Cotman, a neuroscientist at the University of California at Irvine. He found that rats that exercise on a treadmill have raised levels of brain-derived neurotrophic factor coursing through their brains. Cotman believes this hormone, which keeps neurons functioning, may prevent the brains of active humans from deteriorating.
J As part of the same study, Teresa Seeman, a social epidemiologist at the University of Southern California in Los Angeles, found a connection between self-esteem and stress in people over 70. In laboratory simulations of challenging activities such as driving, those who felt in control of their lives pumped out lower levels of stress hormones such as cortisol. Chronically high levels of these hormones have been linked to heart disease.
K But independence can have drawbacks. Seeman found that elderly people who felt emotionally isolated maintained higher levels of stress hormones even when asleep. The research suggests that older people fare best when they feel independent but know they can get help when they need it.
L 'Like much research into ageing, these results support common sense,' says Seeman. They also show that we may be underestimating the impact of these simple factors. 'The sort of thing that your grandmother always told you turns out to be right on target,' she says.
B In the last 14 years, the National Long-term Health Care Survey has gathered data on the health and lifestyles of more than 20,000 men and women over 65. Researchers, now analysing the results of data gathered in 1994, say arthritis, high blood pressure and circulation problems - the major medical complaints in this age group - are troubling a smaller proportion every year. And the data confirms that the rate at which these diseases are declining continues to accelerate. Other diseases of old age - dementia, stroke, arteriosclerosis and emphysema - are also troubling fewer and fewer people.
C 'It really raises the question of what should be considered normal ageing,' says Kenneth Manton, a demographer from Duke University in North Carolina. He says the problems doctors accepted as normal in a 65-year-old in 1982 are often not appearing until people are 70 or 75.
D Clearly, certain diseases are beating a retreat in the face of medical advances. But there may be other contributing factors. Improvements in childhood nutrition in the first quarter of the twentieth century, for example, gave today's elderly people a better start in life than their predecessors.
E On the downside, the data also reveals failures in public health that have caused surges in some illnesses. An increase in some cancers and bronchitis may reflect changing smoking habits and poorer air quality, say the researchers. These may be subtle influences,' says Manton, 'but our subjects have been exposed to worse and worse pollution for over 60 years.It's not surprising we see some effect'.
F One interesting correlation Manton uncovered is that better-educated people are likely to live longer. For example, 65-year-old women with fewer than eight years of schooling are expected, on average, to live to 82. Those who continued their education live an extra seven years. Although some of this can be attributed to a higher income, Manton believes it is mainly because educated people seek more medical attention.
G The survey also assessed how independent people over 65 were, and again found a striking trend. Almost 80% of those in the 1994 survey could complete everyday activities ranging from eating and dressing unaided to complex tasks such as cooking and managing their finances. That represents a significant drop in the number of disabled old people in the population. If the trends apparent in the United States 14 years ago had continued, researchers calculate there would be an additional one million disabled elderly people in today's population. According to Manton, slowing the trend has saved the United States government's Medicare system more than $200 billion, suggesting that the greying of America's population may prove less of a financial burden than expected.
H The increasing self-reliance of many elderly people is probably linked to a massive increase in the use of simple home medical aids. For instance, the use of raised toilet seats has more than doubled since the start of the study, and the use of bath seats has grown by more than 50%. These developments also bring some health benefits, according to a report from the MacArthur Foundation's research group on successful ageing. The group found that those elderly people who were able to retain a sense of independence were more likely to stay healthy in old age.
I Maintaining a level of daily physical activity may help mental functioning, says Carl Cotman, a neuroscientist at the University of California at Irvine. He found that rats that exercise on a treadmill have raised levels of brain-derived neurotrophic factor coursing through their brains. Cotman believes this hormone, which keeps neurons functioning, may prevent the brains of active humans from deteriorating.
J As part of the same study, Teresa Seeman, a social epidemiologist at the University of Southern California in Los Angeles, found a connection between self-esteem and stress in people over 70. In laboratory simulations of challenging activities such as driving, those who felt in control of their lives pumped out lower levels of stress hormones such as cortisol. Chronically high levels of these hormones have been linked to heart disease.
K But independence can have drawbacks. Seeman found that elderly people who felt emotionally isolated maintained higher levels of stress hormones even when asleep. The research suggests that older people fare best when they feel independent but know they can get help when they need it.
L 'Like much research into ageing, these results support common sense,' says Seeman. They also show that we may be underestimating the impact of these simple factors. 'The sort of thing that your grandmother always told you turns out to be right on target,' she says.
Part 3
Read the text and answer questions 28–40.
TITLE 3
A
PARA3
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