The future of old age
We're all living longer. But will this just mean more pain and immobility? Or could science cure the illnesses of old age? Alok Jha reports
Wednesday March 8, 2006
The Guardian
Every minute that you spend reading this article, the average life expectancy in Britain will rise by 12 seconds. By the time you finish reading g2, your life expectancy will have gone up by six minutes. This time tomorrow, it will have increased by almost five hours. The reason is clear: rapid advances in medicine and biology have been one of the biggest achievements of the past century and we are all living longer. Where anyone reaching the age of 60 was considered to be near death's door at the turn of the 20th century, it is barely old enough for retirement at the turn of the 21st century.
And scientists are still not holding back. Shripad Tuljapurkar, a population studies expert at Stanford University, told a recent meeting of the American Association for the Advancement of Science that, as new anti-ageing treatments become available, our species will get even older. Soon, the average age of death will jump by a year every year - five times the current rate.
While few would argue that living longer is an attractive idea, the rapid increase in the number of years begs a question: what will life be like for our increasingly elderly population? Is it such a good idea to live for an extra decade if it just involves 10 more years of illness or frailty?
"What we really want is our health expectancy to be as close as possible to our life expectancy, so that we live long and die quickly," says Lorna Layward, research manager at the charity Research into Ageing. "In other words, we [want to] compress the time we are ill at the end of our lives."
But is that possible? Getting into the specifics of this is difficult simply because each individual will have different diseases and suffer from them in a different way. The state of our bones, muscles, hearts, brains and immune systems over time depends on a range of factors, from genetics and what kind of environment we have lived in to the medical care available to us and even our level of education. But there is no doubt that getting older is the biggest single risk factor in a host of diseases from dementia to cancer.
Calculating an individual's chances of good health in old age are therefore tricky. But scientists are beginning to find that, at the population level, the time we are likely to spend ill at the end of our ever-increasing lives will drop thanks to medical advances and our increased awareness of how to stay healthy.
Quality of life is already improving for the elderly. "If you look at what a 70-year-old person is doing now versus what a 70-year-old person was doing 50 years ago, it's totally different," says Arlan Richardson, director of the Barshop Institute for Ageing and Longevity research, University of Texas. "All you've got to look at is [the astronaut] John Glenn, who went [into space] when he was 77. Three out of four of my grandparents died before they were 75 years of age, let alone going [into space]."
But long-term illness will still have to be endured by most elderly people, according to Ann Bowling, a population scientist at University College London. "Whether it's cancers or heart disease, they're not going to go away but they are becoming more treatable. People are less likely to die from those, but we're more likely to have to live with them. So people aren't necessarily dying of their heart attack, but they're living with their rheumatism instead, or even chronic cancers."
Predictions for future health expectancy have changed over the past few decades. "In the 1980s, life expectancy was increasing and the best data that we had suggested that for every increased year of life expectancy, a greater fraction was disabled life expectancy," says Richard Suzman, director of the social and behavioural research programme at the US National Institute on Ageing. "That led to a pessimistic perception that what we would see was a piling up of chronic illness and related disability, that medical science could extend life but it couldn't prevent disability or cure it."
But that world view changed suddenly in the early 1990s with the publication of a study by researchers at Duke University, who had been following the health of 20,000 people for almost a decade. They showed that disability among the elderly was not only dropping, but it was doing so at an ever-increasing rate.
Looking at their volunteers in 1994, the Duke researchers had expected a quarter of their volunteers to be disabled if rates had stayed the same as those in 1982. Instead, only 21% of the people were disabled, equivalent to 1.2m fewer disabled people than would have been without better health. According to the researchers, this represented a relative decline of almost 15%, most of it thanks to improved education on health risks and better healthcare.
This is certainly encouraging for Americans. For Britons, the picture is not as rosy. "When you look at European and US data, it seems more clear cut that there is more evidence in favour of disability-free and healthy life expectancy. In this country, the data is more cloudy," says Bowling.
Evidence presented to the House of Lords science committee's inquiry into ageing in 2002 indicated that health expectancy seems to be growing more slowly than life expectancy in Britain and that the period of debilitating illness at the end of our lives was, in fact, increasing. The Office of National Statistics, which provided the information, warned that the research was based on self-reporting of illness, so the reliability of the assessments was uncertain. Using them to project into the future would therefore be difficult.
There was a time when biologists believed ageing was controlled by some inner mechanism that imposes an upper limit on lifespan. But this explanation has fallen out of favour, replaced by the idea that ageing is simply a build-up of tiny faults and waste products as our cells go about their daily business. In addition, the body starts to streamline itself after the age of 30. Between the ages of 30 and 80, a person will lose 40% of their muscle mass, for example. Not only do we lose muscle fibres, but the ones left behind are weaker.
The story is similar with our bones: the strength and mass of the skeleton rises until the early 30s, after which men will lose about 1% of their bone mass per decade. Women lose bone at the same rate in the 10-year run-up to menopause, but, on reaching the menopause, their rate of loss jumps to about 1% per year for several years before going back to the same rate as men. "In five years, women's skeletons age by 50 years compared with men," says Tim Skerry, a professor of orthopaedic biology at Sheffield University.
Weaker muscles mean an inability to move quickly or to react appropriately to prevent a fall, for example. And weaker bones mean that they are more likely to break. Cancer is a significant cause of death in all age groups, but the absolute rate of death increases sharply with age. According to Cancer Research UK, more than 140,000 people over the age of 70 are diagnosed with cancer every year, of which more than 100,000 people in this age group die, with the most common reasons being lung, prostate, breast and colorectal cancers. If the current incidence of cancer stays unchanged, which looks likely, there will be an extra 100,000 cases diagnosed annually and the vast majority will be in those over 70.
Perhaps the most striking degradation happens to the brain. After the age of 40, the brain decreases in volume and weight by 5% every decade. This shrinkage affects people differently - while some people will be relatively unaffected, others will get more forgetful as time passes and could eventually develop Alzheimer's disease.
But the slew of drugs and treatments dealing with the problems of age continue to arrive. Researchers in the US are studying the use of anabolic steroids to build up muscle mass, for example. In the UK, Malcolm Jackson of the University of Liverpool is focusing on trying to find drugs that prevent deterioration of muscle mass in the first place. Stem cells, the body's master cells that can grow into any type of tissue in the body, could also help. "The people doing work in that area believe that it will be possible, certainly in disease states, to help replace diseased muscle. It's not a big step from that to the ageing muscle as well," says Jackson.
The damage caused to the heart in heart disease could also be repaired by studying stem cells. Understanding how the cells are made will allow the development of treatments to induce a mature heart cell to start dividing, something it would not normally do.
Skerry says that drugs to stop bones wasting away are already available. "If you have a fracture because of osteoporosis, you can prevent further bone loss. But by the time you've got a fracture, much of your skeleton is already weaker than it should be. So stopping further loss is good, but it's not the whole answer," he says.
Stimulating bone to grow again is the goal for many scientists, however. "I'm very optimistic. Current research is going very much in that direction and there are a few drugs that stimulate bone formation," says Skerry.
Arthritis, the result of wear and tear on the joints of the body, affects 7m adults in the UK and causes a great deal of long-term problems. Scientists suspect that several genes could be implicated in the development of this and related conditions - how that information will end up being used to improve life for sufferers (either in terms of drugs to target joints or treatments that work on the genes) is still an open question.
There is good news in other areas, however. Mortality rates with hip fractures are already improving: nowadays, 20% of people die a year after fracturing their hip; 10 years ago, that figure was 35%. As hip replacement procedures become more efficient (with longer-lasting replacements made of lighter materials) the trauma for the patients (who will be healthier in their old age anyway and better able to cope with such surgery) will decrease.
The sticking point to this progress could be the brain. There is no known cure for dementia as yet and leads are thin on the ground. Laboratory-based techniques trying to immunise against certain types of brain degeneration or slowing down the degradation have worked in animals but not, so far, in humans. Carol Brayne, a professor of public health medicine at Cambridge University, told the Lords' inquiry that she thought it "very unlikely that [any current technique] is going to make an impact on old-age dementia, certainly in the near future and maybe in the longer term".
Richardson has further reservations. "We have people living now who are older than we've ever had. The question is whether we've done anything about the ageing process or we're treating diseases more effectively," he says. "People in their 70s are healthier than they were 50 years ago but, on the other hand, I don't see, unless we do something about ageing, that, 20 years from now, a 70- or an 80-year-old person will be any healthier than they are now."
He argues that quality of life for the elderly will never improve dramatically until scientists look further at the mechanisms behind, rather than the symptoms of, ageing. It is a subject avoided by many scientists until recently. "Until the past five years, there was not a lot of interest in putting money into ageing research - one reason was the belief that you couldn't do anything about it," says Richardson. "The other thing is if you do slow down the ageing process, maybe that'll be bad because we'll just have more people in nursing homes."
But the tide is turning. Studies into genetic factors behind ageing have shown that there is no single gene responsible. Rather, several parts of our genome have been linked to the cumulative effect that makes us age. Restrict how much an animal eats, for example, and it will live longer. In lab experiments, rats on calorie-restricted diets were found to be physiologically younger, got diseases later in later in life and, at any rate, had less severe cases. "From the rodent models that have been looked at, the increase in lifespan is usually in the range of 15-30% maximum," says Richardson. Cutting calories is thought to trigger a switch in an animal's behaviour from normal to a state of stasis in which growth and ageing are temporarily put on hold. When food becomes available again, the animal's behaviour switches back.
Valter Longo, a biomedical gerontologist at the University of Southern California recently made yeast cells live six times longer than normal by blocking the action of two genes that, he claims, are part of the fundamental mechanism that controls how living things age. One of the genes governs the yeast's ability to convert food into energy, the other plays a role in directing energy from food into growth and reproduction, ie normal behaviour. By suppressing these two genes, the yeast cells were tricked into thinking food was scarce and forced into survival mode, living for six weeks instead of their usual one-week lifespan.
Richardson predicts that understanding the mechanisms behind calorie restriction and other genetic reasons behind ageing could be used within the next two decades to give people several extra healthy years of life. It will be a complicated field: the single-celled yeast is a simple organism and at least 10 genes have been identified that have some subtle effect on how it ages. How many genes affect ageing in humans remains to be seen.
Improving the quality of life of the elderly should be a critical part of medical research, according to Layward. "If people are well, they are not a problem. If people are healthy, they will want to stay in work, will want to be consumers, will contribute to taxes, will not be taking all their pensions," she says.
Aubrey de Grey, a biomedical gerontologist at Cambridge University, has raised hackles among scientists by suggesting that ageing could one day be stopped altogether, leading to healthy lifespans of hundreds of years. His ideas range from using stem cells to regrow diseased tissue to more left-field suggestions such as implanting people with bacteria that can clean up the waste that builds up inside cells.
Richardson says that thinking about stopping ageing is a "little bit silly" at the moment but doesn't dismiss it altogether, arguing that none of the illnesses related to ageing should be inevitable. He says that achieving longer healthy life - an average of 100 or even beyond - is all about the quality of the maintenance. "I would agree with De Grey in that respect - possibly you could stop ageing in its tracks," he says. Start with a high-quality body (and that means eating your greens, not smoking and doing lots of exercise in your younger days) and you can keep it going for longer with due care and attention. "It's like the difference between a Rolls-Royce and a cheap car".
Wednesday March 8, 2006
The Guardian
Every minute that you spend reading this article, the average life expectancy in Britain will rise by 12 seconds. By the time you finish reading g2, your life expectancy will have gone up by six minutes. This time tomorrow, it will have increased by almost five hours. The reason is clear: rapid advances in medicine and biology have been one of the biggest achievements of the past century and we are all living longer. Where anyone reaching the age of 60 was considered to be near death's door at the turn of the 20th century, it is barely old enough for retirement at the turn of the 21st century.
And scientists are still not holding back. Shripad Tuljapurkar, a population studies expert at Stanford University, told a recent meeting of the American Association for the Advancement of Science that, as new anti-ageing treatments become available, our species will get even older. Soon, the average age of death will jump by a year every year - five times the current rate.
While few would argue that living longer is an attractive idea, the rapid increase in the number of years begs a question: what will life be like for our increasingly elderly population? Is it such a good idea to live for an extra decade if it just involves 10 more years of illness or frailty?
"What we really want is our health expectancy to be as close as possible to our life expectancy, so that we live long and die quickly," says Lorna Layward, research manager at the charity Research into Ageing. "In other words, we [want to] compress the time we are ill at the end of our lives."
But is that possible? Getting into the specifics of this is difficult simply because each individual will have different diseases and suffer from them in a different way. The state of our bones, muscles, hearts, brains and immune systems over time depends on a range of factors, from genetics and what kind of environment we have lived in to the medical care available to us and even our level of education. But there is no doubt that getting older is the biggest single risk factor in a host of diseases from dementia to cancer.
Calculating an individual's chances of good health in old age are therefore tricky. But scientists are beginning to find that, at the population level, the time we are likely to spend ill at the end of our ever-increasing lives will drop thanks to medical advances and our increased awareness of how to stay healthy.
Quality of life is already improving for the elderly. "If you look at what a 70-year-old person is doing now versus what a 70-year-old person was doing 50 years ago, it's totally different," says Arlan Richardson, director of the Barshop Institute for Ageing and Longevity research, University of Texas. "All you've got to look at is [the astronaut] John Glenn, who went [into space] when he was 77. Three out of four of my grandparents died before they were 75 years of age, let alone going [into space]."
But long-term illness will still have to be endured by most elderly people, according to Ann Bowling, a population scientist at University College London. "Whether it's cancers or heart disease, they're not going to go away but they are becoming more treatable. People are less likely to die from those, but we're more likely to have to live with them. So people aren't necessarily dying of their heart attack, but they're living with their rheumatism instead, or even chronic cancers."
Predictions for future health expectancy have changed over the past few decades. "In the 1980s, life expectancy was increasing and the best data that we had suggested that for every increased year of life expectancy, a greater fraction was disabled life expectancy," says Richard Suzman, director of the social and behavioural research programme at the US National Institute on Ageing. "That led to a pessimistic perception that what we would see was a piling up of chronic illness and related disability, that medical science could extend life but it couldn't prevent disability or cure it."
But that world view changed suddenly in the early 1990s with the publication of a study by researchers at Duke University, who had been following the health of 20,000 people for almost a decade. They showed that disability among the elderly was not only dropping, but it was doing so at an ever-increasing rate.
Looking at their volunteers in 1994, the Duke researchers had expected a quarter of their volunteers to be disabled if rates had stayed the same as those in 1982. Instead, only 21% of the people were disabled, equivalent to 1.2m fewer disabled people than would have been without better health. According to the researchers, this represented a relative decline of almost 15%, most of it thanks to improved education on health risks and better healthcare.
This is certainly encouraging for Americans. For Britons, the picture is not as rosy. "When you look at European and US data, it seems more clear cut that there is more evidence in favour of disability-free and healthy life expectancy. In this country, the data is more cloudy," says Bowling.
Evidence presented to the House of Lords science committee's inquiry into ageing in 2002 indicated that health expectancy seems to be growing more slowly than life expectancy in Britain and that the period of debilitating illness at the end of our lives was, in fact, increasing. The Office of National Statistics, which provided the information, warned that the research was based on self-reporting of illness, so the reliability of the assessments was uncertain. Using them to project into the future would therefore be difficult.
There was a time when biologists believed ageing was controlled by some inner mechanism that imposes an upper limit on lifespan. But this explanation has fallen out of favour, replaced by the idea that ageing is simply a build-up of tiny faults and waste products as our cells go about their daily business. In addition, the body starts to streamline itself after the age of 30. Between the ages of 30 and 80, a person will lose 40% of their muscle mass, for example. Not only do we lose muscle fibres, but the ones left behind are weaker.
The story is similar with our bones: the strength and mass of the skeleton rises until the early 30s, after which men will lose about 1% of their bone mass per decade. Women lose bone at the same rate in the 10-year run-up to menopause, but, on reaching the menopause, their rate of loss jumps to about 1% per year for several years before going back to the same rate as men. "In five years, women's skeletons age by 50 years compared with men," says Tim Skerry, a professor of orthopaedic biology at Sheffield University.
Weaker muscles mean an inability to move quickly or to react appropriately to prevent a fall, for example. And weaker bones mean that they are more likely to break. Cancer is a significant cause of death in all age groups, but the absolute rate of death increases sharply with age. According to Cancer Research UK, more than 140,000 people over the age of 70 are diagnosed with cancer every year, of which more than 100,000 people in this age group die, with the most common reasons being lung, prostate, breast and colorectal cancers. If the current incidence of cancer stays unchanged, which looks likely, there will be an extra 100,000 cases diagnosed annually and the vast majority will be in those over 70.
Perhaps the most striking degradation happens to the brain. After the age of 40, the brain decreases in volume and weight by 5% every decade. This shrinkage affects people differently - while some people will be relatively unaffected, others will get more forgetful as time passes and could eventually develop Alzheimer's disease.
But the slew of drugs and treatments dealing with the problems of age continue to arrive. Researchers in the US are studying the use of anabolic steroids to build up muscle mass, for example. In the UK, Malcolm Jackson of the University of Liverpool is focusing on trying to find drugs that prevent deterioration of muscle mass in the first place. Stem cells, the body's master cells that can grow into any type of tissue in the body, could also help. "The people doing work in that area believe that it will be possible, certainly in disease states, to help replace diseased muscle. It's not a big step from that to the ageing muscle as well," says Jackson.
The damage caused to the heart in heart disease could also be repaired by studying stem cells. Understanding how the cells are made will allow the development of treatments to induce a mature heart cell to start dividing, something it would not normally do.
Skerry says that drugs to stop bones wasting away are already available. "If you have a fracture because of osteoporosis, you can prevent further bone loss. But by the time you've got a fracture, much of your skeleton is already weaker than it should be. So stopping further loss is good, but it's not the whole answer," he says.
Stimulating bone to grow again is the goal for many scientists, however. "I'm very optimistic. Current research is going very much in that direction and there are a few drugs that stimulate bone formation," says Skerry.
Arthritis, the result of wear and tear on the joints of the body, affects 7m adults in the UK and causes a great deal of long-term problems. Scientists suspect that several genes could be implicated in the development of this and related conditions - how that information will end up being used to improve life for sufferers (either in terms of drugs to target joints or treatments that work on the genes) is still an open question.
There is good news in other areas, however. Mortality rates with hip fractures are already improving: nowadays, 20% of people die a year after fracturing their hip; 10 years ago, that figure was 35%. As hip replacement procedures become more efficient (with longer-lasting replacements made of lighter materials) the trauma for the patients (who will be healthier in their old age anyway and better able to cope with such surgery) will decrease.
The sticking point to this progress could be the brain. There is no known cure for dementia as yet and leads are thin on the ground. Laboratory-based techniques trying to immunise against certain types of brain degeneration or slowing down the degradation have worked in animals but not, so far, in humans. Carol Brayne, a professor of public health medicine at Cambridge University, told the Lords' inquiry that she thought it "very unlikely that [any current technique] is going to make an impact on old-age dementia, certainly in the near future and maybe in the longer term".
Richardson has further reservations. "We have people living now who are older than we've ever had. The question is whether we've done anything about the ageing process or we're treating diseases more effectively," he says. "People in their 70s are healthier than they were 50 years ago but, on the other hand, I don't see, unless we do something about ageing, that, 20 years from now, a 70- or an 80-year-old person will be any healthier than they are now."
He argues that quality of life for the elderly will never improve dramatically until scientists look further at the mechanisms behind, rather than the symptoms of, ageing. It is a subject avoided by many scientists until recently. "Until the past five years, there was not a lot of interest in putting money into ageing research - one reason was the belief that you couldn't do anything about it," says Richardson. "The other thing is if you do slow down the ageing process, maybe that'll be bad because we'll just have more people in nursing homes."
But the tide is turning. Studies into genetic factors behind ageing have shown that there is no single gene responsible. Rather, several parts of our genome have been linked to the cumulative effect that makes us age. Restrict how much an animal eats, for example, and it will live longer. In lab experiments, rats on calorie-restricted diets were found to be physiologically younger, got diseases later in later in life and, at any rate, had less severe cases. "From the rodent models that have been looked at, the increase in lifespan is usually in the range of 15-30% maximum," says Richardson. Cutting calories is thought to trigger a switch in an animal's behaviour from normal to a state of stasis in which growth and ageing are temporarily put on hold. When food becomes available again, the animal's behaviour switches back.
Valter Longo, a biomedical gerontologist at the University of Southern California recently made yeast cells live six times longer than normal by blocking the action of two genes that, he claims, are part of the fundamental mechanism that controls how living things age. One of the genes governs the yeast's ability to convert food into energy, the other plays a role in directing energy from food into growth and reproduction, ie normal behaviour. By suppressing these two genes, the yeast cells were tricked into thinking food was scarce and forced into survival mode, living for six weeks instead of their usual one-week lifespan.
Richardson predicts that understanding the mechanisms behind calorie restriction and other genetic reasons behind ageing could be used within the next two decades to give people several extra healthy years of life. It will be a complicated field: the single-celled yeast is a simple organism and at least 10 genes have been identified that have some subtle effect on how it ages. How many genes affect ageing in humans remains to be seen.
Improving the quality of life of the elderly should be a critical part of medical research, according to Layward. "If people are well, they are not a problem. If people are healthy, they will want to stay in work, will want to be consumers, will contribute to taxes, will not be taking all their pensions," she says.
Aubrey de Grey, a biomedical gerontologist at Cambridge University, has raised hackles among scientists by suggesting that ageing could one day be stopped altogether, leading to healthy lifespans of hundreds of years. His ideas range from using stem cells to regrow diseased tissue to more left-field suggestions such as implanting people with bacteria that can clean up the waste that builds up inside cells.
Richardson says that thinking about stopping ageing is a "little bit silly" at the moment but doesn't dismiss it altogether, arguing that none of the illnesses related to ageing should be inevitable. He says that achieving longer healthy life - an average of 100 or even beyond - is all about the quality of the maintenance. "I would agree with De Grey in that respect - possibly you could stop ageing in its tracks," he says. Start with a high-quality body (and that means eating your greens, not smoking and doing lots of exercise in your younger days) and you can keep it going for longer with due care and attention. "It's like the difference between a Rolls-Royce and a cheap car".