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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.
DELIVERING THE GOODS
The vast expansion in international trade owes much to a revolution in the business of moving freight.
A
International trade is growing at a startling pace.
While the global economy has been expanding at a bit over 3% a year, the volume of trade has been rising at a compound annual rate of about twice that.
Foreign products, from meat to machinery, play a more important role in almost every economy in the world, and foreign markets now tempt businesses that never much worried about sales beyond their nation's borders.
B What lies behind this explosion in international commerce? The general worldwide decline in trade barriers, such as customs duties and import quotas, is surely one explanation. The economic opening of countries that have traditionally been minor players is another. But one force behind the import-export boom has passed all but unnoticed: the rapidly falling cost of getting goods to market. Theoretically, in the world of trade, shipping costs do not matter. Goods, once they have been made, are assumed to move instantly and at no cost from place to place. The real world, however, is full of frictions. Cheap labour may make Chinese clothing competitive in America, but if delays in shipment tie up working capital and cause winter coats to arrive in spring, trade may lose its advantages.
C At the turn of the 20th century, agriculture and manufacturing were the two most important sectors almost everywhere, accounting for about 70% of total output in Germany, Italy and France, and 40-50% in America, Britain and Japan. International commerce was therefore dominated by raw materials, such as wheat, wood and iron ore, or processed commodities, such as meat and steel. But these sorts of products are heavy and bulky and the cost of transporting them relatively high.
D Countries still trade disproportionately with their geographic neighbours. Over time, however, world output has shifted into goods whose worth is unrelated to their size and weight. Today, it is finished manufactured products that dominate the flow of trade, and, thanks to technological advances such as lightweight components, manufactured goods themselves have tended to become lighter and less bulky. As a result, less transportation is required for every dollar's worth of imports or exports.
E To see how this influences trade, consider the business of making disk drives for computers. Most of the world's disk-drive manufacturing is concentrated in South-east Asia. This is possible only because disk drives, while valuable, are small and light and so cost little to ship. Computer manufacturers in Japan or Texas will not face hugely bigger freight bills if they import drives from Singapore rather than purchasing them on the domestic market. Distance therefore poses no obstacle to the globalisation of the disk-drive industry.
F This is even more true of the fast-growing information industries. Films and compact discs cost little to transport, even by aeroplane. Computer software can be ‘exported' without ever loading it onto a ship, simply by transmitting it over telephone lines from one country to another, so freight rates and cargo-handling schedules become insignificant factors in deciding where to make the product. Businesses can locate based on other considerations, such as the availability of labour, while worrying less about the cost of delivering their output.
G In many countries deregulation has helped to drive the process along. But, behind the scenes, a series of technological innovations known broadly as containerisation and intermodal transportation has led to swift productivity improvements in cargo-handling. Forty years ago, the process of exporting or importing involved a great many stages of handling, which risked portions of the shipment being damaged or stolen along the way. The invention of the container crane made it possible to load and unload containers without capsizing the ship and the adoption of standard container sizes allowed almost any box to be transported on any ship. By 1967, dual-purpose ships, carrying loose cargo in the hold* and containers on the deck, were giving way to all-container vessels that moved thousands of boxes at a time.
H The shipping container transformed ocean shipping into a highly efficient, intensely competitive business. But getting the cargo to and from the dock was a different story. National governments, by and large, kept a much firmer hand on truck and railroad tariffs than on charges for ocean freight. This started changing, however, in the mid-1970s, when America began to deregulate its transportation industry. First airlines, then road hauliers and railways, were freed from restrictions on what they could carry, where they could haul it and what price they could charge. Big productivity gains resulted. Between 1985 and 1996, for example, America's freight railways dramatically reduced their employment, trackage, and their fleets of locomotives - while increasing the amount of cargo they hauled. Europe's railways have also shown marked, albeit smaller, productivity improvements.
I In America the period of huge productivity gains in transportation may be almost over, but in most countries the process still has far to go. State ownership of railways and airlines, regulation of freight rates and toleration of anti-competitive practices, such as cargo-handling monopolies, all keep the cost of shipping unnecessarily high and deter international trade. Bringing these barriers down would help the world's economies grow even closer.
* hold: ship's storage area below deck.
* hold: ship's storage area below deck
B What lies behind this explosion in international commerce? The general worldwide decline in trade barriers, such as customs duties and import quotas, is surely one explanation. The economic opening of countries that have traditionally been minor players is another. But one force behind the import-export boom has passed all but unnoticed: the rapidly falling cost of getting goods to market. Theoretically, in the world of trade, shipping costs do not matter. Goods, once they have been made, are assumed to move instantly and at no cost from place to place. The real world, however, is full of frictions. Cheap labour may make Chinese clothing competitive in America, but if delays in shipment tie up working capital and cause winter coats to arrive in spring, trade may lose its advantages.
C At the turn of the 20th century, agriculture and manufacturing were the two most important sectors almost everywhere, accounting for about 70% of total output in Germany, Italy and France, and 40-50% in America, Britain and Japan. International commerce was therefore dominated by raw materials, such as wheat, wood and iron ore, or processed commodities, such as meat and steel. But these sorts of products are heavy and bulky and the cost of transporting them relatively high.
D Countries still trade disproportionately with their geographic neighbours. Over time, however, world output has shifted into goods whose worth is unrelated to their size and weight. Today, it is finished manufactured products that dominate the flow of trade, and, thanks to technological advances such as lightweight components, manufactured goods themselves have tended to become lighter and less bulky. As a result, less transportation is required for every dollar's worth of imports or exports.
E To see how this influences trade, consider the business of making disk drives for computers. Most of the world's disk-drive manufacturing is concentrated in South-east Asia. This is possible only because disk drives, while valuable, are small and light and so cost little to ship. Computer manufacturers in Japan or Texas will not face hugely bigger freight bills if they import drives from Singapore rather than purchasing them on the domestic market. Distance therefore poses no obstacle to the globalisation of the disk-drive industry.
F This is even more true of the fast-growing information industries. Films and compact discs cost little to transport, even by aeroplane. Computer software can be ‘exported' without ever loading it onto a ship, simply by transmitting it over telephone lines from one country to another, so freight rates and cargo-handling schedules become insignificant factors in deciding where to make the product. Businesses can locate based on other considerations, such as the availability of labour, while worrying less about the cost of delivering their output.
G In many countries deregulation has helped to drive the process along. But, behind the scenes, a series of technological innovations known broadly as containerisation and intermodal transportation has led to swift productivity improvements in cargo-handling. Forty years ago, the process of exporting or importing involved a great many stages of handling, which risked portions of the shipment being damaged or stolen along the way. The invention of the container crane made it possible to load and unload containers without capsizing the ship and the adoption of standard container sizes allowed almost any box to be transported on any ship. By 1967, dual-purpose ships, carrying loose cargo in the hold* and containers on the deck, were giving way to all-container vessels that moved thousands of boxes at a time.
H The shipping container transformed ocean shipping into a highly efficient, intensely competitive business. But getting the cargo to and from the dock was a different story. National governments, by and large, kept a much firmer hand on truck and railroad tariffs than on charges for ocean freight. This started changing, however, in the mid-1970s, when America began to deregulate its transportation industry. First airlines, then road hauliers and railways, were freed from restrictions on what they could carry, where they could haul it and what price they could charge. Big productivity gains resulted. Between 1985 and 1996, for example, America's freight railways dramatically reduced their employment, trackage, and their fleets of locomotives - while increasing the amount of cargo they hauled. Europe's railways have also shown marked, albeit smaller, productivity improvements.
I In America the period of huge productivity gains in transportation may be almost over, but in most countries the process still has far to go. State ownership of railways and airlines, regulation of freight rates and toleration of anti-competitive practices, such as cargo-handling monopolies, all keep the cost of shipping unnecessarily high and deter international trade. Bringing these barriers down would help the world's economies grow even closer.
* hold: ship's storage area below deck.
* hold: ship's storage area below deck
Part 3
Read the text and answer questions 28–40.
TITLE 3
A
PARA3
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