Dr Graham Easton splits his week between working as a GP in west London and producing and presenting science and medical programmes for BBC Radio.
So will we live forever?
An important part of my daily routine as a GP is the ritual prodding and shouting at newspapers. Headlines like 'Could this be a cure for Cancer?' may be great for sales but they're nothing but a cruel tease for Mrs Smith waiting to have her mastectomy. But I wouldn't be so cynical about "One Day We'll All Live to be a Hundred"; I'm not talking about a magical elixir of eternal youth, but I do think the human life span will gradually get longer and longer. Though as a doctor, what worries me is how we'll all cope.
Since the 1950's our average life span has been stretching by about 2 years every decade; and that's nothing to do with a magical elixir. My six-month-old son can expect to live about 8 years longer than I will. That's because we're eating better, there's better sanitation, we've got antibiotics and vaccinations and we're fighting the big killers like heart disease on several fronts - diet, exercise, and keeping our cholesterol and blood pressure nice and low. I think we'll use the same shotgun tactics to keep chipping away at the human life span in the future.
Just like heart disease, or cancer, ageing itself is driven by a mixture of our genes, and by the way we live our lives. Our genes account for only a quarter of what determines how old we live. No one knows exactly what these genes are yet, or what they do, but there have been tantalising glimpses in the form of wrinkled and arthritic mice and "Peter Pan" worms and fruit flies. With the Human Genome Project now up and running, it won't be long before scientists find the human genes that are beavering away repairing our cells and DNA, trying desperately to keep us young. But even if we found them all, worked out what they did, and then harnessed them to our advantage, we still wouldn't have the "magic bullet" against ageing.
Some scientists are making headway in stopping the biological clocks within every cell - the so-called 'telomeres' that sit like short fuses burning away at the end of our chromosomes. Others are already trying to use fresh, young, stem cells to replace worn-out body parts like the brain or the heart. Alongside all this genetic work, we're learning more about how calorie intake, antioxidants like Vitamin C, exercise, sunlight and smoking all affect the ageing process. No magic elixir then, but it's easy to see how some or all of these strands of research will, in time, carry us through the century barrier.
But as any frontline GP will tell you, the real challenges of old age are human, not scientific. In today's society older people are often marginalized: immobile, needing care, unproductive and therefore seen as a nuisance to society. How will we cope when 80 year-olds outnumber 30 year-olds? Unless there are great leaps in quality of life, as well as quantity, I doubt many of us would even want to live to be a hundred. So while the scientists focus on our ageing cells and genes, the rest of us need to think about what we'll do with the whole ancient organism.
Professor Tom Kirkwood - expert on the science of ageing, based at the Institute for Ageing and Health at the University of Newcastle. He gave the 2001 Reith Lecture for Radio 4, and is the author of 'Time of Our Lives - Why ageing is neither inevitable nor necessary'.
How has the average age of death changed over the past century?
At the moment, life expectancy at birth in Britain is 75 years for a man and 80 years for a woman. This has increased quite steadily over the century just passed. What we've seen particularly is that during the half century from 1950 life span has increased on the average by two years a decade and I think many people expected that these increases in life expectancy would begin to slow down as we got rid of the premature causes of death and enabled people to live to the limit of their biological potential. But actually something very interesting is happening now, and what we're seeing is that death rates at older ages are continuing to fall and life expectancy is continuing to edge upwards, so at the moment there's no immediate sign of this process coming to a natural limit.
To what extent do we inherit long life?
It's very interesting now to look at what determines how long we might expect to live. Of course, part of it's down to our genes and now there have been quite a lot of studies that have looked at the genetic contribution to longevity. These show consistently that something in the region of a quarter of what determines the length of our lives is genetic. So long life does run in families, but it's not as deterministic as the inheritance of blood group or eye colour - if you have an inheritance of just a quarter, that means that three quarters are determined by other things, and this means that many important factors of the ageing process are influenced by things like lifestyle, nutrition and exercise. I think one of the great challenges is to be able to probe the ageing process and understand how the choices that we make in life can make a difference to how long we may live and what kind of shape we may be in when we come to old age.
What is the relationship between the big killer diseases and underlying ageing?
One of the most striking things about the ageing process is that as we get older we become more likely to fall prey to any of a number of diseases which might ultimately kill us - for example cancer, heart disease and Alzheimer's disease (which doesn't necessarily kill us but robs us of our identity and does actually ultimately sort of stop us functioning so that we die of something else with increased risk) - understanding the relationship between these diseases and what we might call the normal ageing process is one of the great challenges of the day.
What we know is that we don't have some in-built genetic mechanism that programs how long we will live and turns on something that kills us - what makes us age is the build up of damage within the cells and organs of our bodies as we live our lives. So we actually need to look in close cellular and molecular detail at the processes that produce ageing or produce age-related disease. What we believe is that although individual diseases might be distinct clinical entities that require a particular course of medical treatment, there's a very strong overlap between the kinds of molecular damage that leads to the overall ageing process and that leads to increased vulnerability to these particular diseases as we get older.
How close are we to a breakthrough in tackling ageing?
I think it would be very helpful for us to get rid of the idea that there is some quick fix for the ageing process and it's just going to be a matter of a few years before scientists discover some genetic switch that can be thrown, some magic substance that will all make us live to 200 years or whatever. I think the reality is that while science is going to increase our understanding of the ageing process dramatically, and allow us to make some very real improvements in quality of life at later ages, it's going to be extremely difficult to postpone this complex process that attacks us on many fronts. It is an immensely challenging and exciting area of science and the advances that we are seeing are comparable to the kind of advances that have been seen in the last 20 years in cancer research, where we've made huge strides in understanding the process. But even these strides have shown us that in fact being able to prevent or cure all kinds of cancers is going to be a much more difficult goal to attain than people used to think perhaps 30 or 40 years ago.
Is research into extending life more important than researching the quality of that life in old age?
When we think about human ageing, the real challenge that we have is to address the quality of the later years. I think very few people would thank us if we extended life but did nothing about the quality. Already we've got a lot of extra years and I think there's great ambivalence about whether this has been an entirely good thing, given that we can expect to spend significant numbers of those years affected by diseases or conditions that rob us of a lot of quality. So, for most older people the priority is not to be able to extend life but to able to address the issues that spoil quality of life in older ages. I think when we're young and have excellent health, excellent quality of life then it's lovely to think in terms of 'yes please, more of the same'. But the reality is we will all become old and if we don't focus on the quality of those later years, in effect adding life to those years rather than adding years to our lives, then we're heading up the wrong path.
What are your top tips for longevity?
Science can give us some pretty good pointers about what we should do if we want to live a long and healthy life. The first thing you should do is choose your parents well, because if you've got long lived parents that gives you a better expectation of long life - but of course that's not an option that's open to us. The other thing you should choose to do is be a woman, because we know that women live on the average about 5 or 6 years longer, but again that's not an option for half of us. But if we look at the other things that are available to us in terms of the choices that we can make in life I think the most important thing to remember is that what makes us age is the build up of damage in our bodies, so we can make choices in life that will give our bodies the best chance of coping with the damage that attacks us.
First of all, we can avoid certain kinds of damage altogether, we know for example that tobacco causes damage to our cells, we see this in the increased of heart disease, the increased risk of cancer that comes from smoking. You can also avoid sunlight that we know damages skin. But there are much more profound things that we now can build into how we try and maintain our bodies through life - nutrition is terribly important, we can avoid foods that damage us, such as fatty foods, and we can seek out foods that we know are good for us. If we think about the things that we put into our body that ultimately will become part of our cellular structure and part of the maintenance system that we have, then we can hope to achieve quite a lot.
We should also think in terms of exercise, exercise is very good for us, it's good for the cardiovascular system, it's good for the general well-being of the muscles and skeleton, but actually there's good evidence that exercise can play a part in slowing down the rates of certain kinds of damage that may contribute to ageing. There are studies that suggest that the muscles of veteran athletes show a slower build up of mutations in the cellular power units that occur with ageing. We also see that mental exercise, exercise that tests our cognitive performance - things like crossword puzzles, playing card games, learning a new language - provides a mental stimulus. Things that engage us psychologically are also beneficial, because psychological well-being is important for physical well-being too, it's a way of maintaining our stress hormones in appropriate balance, it's a way of keeping us perhaps better protected against depression, a very common problem that afflicts far too many older people. So, there's a lot that we can do. We have to take responsibility for our bodies, we only get one body in life, we might as well look after it if we want it to reach old age in good shape.
Dr Alexander Bürkle - a scientist working with Tom Kirkwood's team at the Institute of Ageing and Health in Newcastle. Dr Bürkle is researching a protein called PARP-1, and its function in repairing DNA damage and preventing ageing and cancer in cells.
Could you explain how oxidising damages DNA, affecting the ageing process and the process of cancer formation?
Oxygen is an extremely important molecule for normal cells to work and to survive. Unfortunately, oxygen has also the ability to transform into aggressive molecules called oxygen free radicals, special kinds of oxygen atoms which have the ability to create molecular damage, so they can interfere with the structure and function of biological molecules such as proteins, RNA and DNA. DNA is quite special in this regard, because it is the only way a cell can in the long term store biological information and it is present in a low number of copies in each cell, therefore it is very important that cells maintain their DNA in a perfect or almost perfect state of integrity. Oxiditive damage of DNA means that subtle changes in the structure and in the coding capacity of DNA is introduced, and this molecular damage can lead to mutation of the genetic code, or else it can lead to the situation that genes - specific parts of the DNA - can no longer be transcribed and translated.
This explains the intimate relationship between normal ageing and the process of cancer formation. It is well-known that most types of cancers are age-related diseases, and so researchers have speculated a long time ago that there may be common roots for both phenomena. And actually DNA damage as it is induced by oxidants or by other DNA-damaging compounds, seems to be the driving force of both processes - cancer formation and the ageing process at large. Therefore we firmly believe that if we unravel and understand the molecular mechanisms leading to DNA damage and its repair we will get a good understanding both of the ageing process and of the process of carcenogenesis.
What results have you got so far from your research into DNA damage?
The gene we are particularly focussing on in my research group is called Parp 1 and this gene encodes a protein which is one of the tools the cell has in its toolbox to fix and repair genetic damage. Parp1 seems to be the sensor of DNA damage, oxiditive DNA damage for instance, and so we are extremely interested in learning what the role and the function of Parp 1 is, both in the process of ageing and in the process of carcenogenesis. Research started some years ago found that the longer lived an animal species was, the more proficient this repair tool turned out to be in blood cells we had studied. Very recently we found that Parp 1 is actually a key regulator and modulator of genomic stability. This is a significant discovery because if there's too much genomic instability going on the cell can either die because it will end up in a totally dysfunctional or non-functional state, or else it can be transformed into a malignant tumour cell that has fully maintained the capacity to grow, but has completely escaped any control of its growth.
How can diet affect cell damage and therefore the ageing process?
Ageing is clearly a multi-factorial phenomenon, it is controlled both by genetic factors and environmental factors. An important environmental factor is, of course, diet which can modulate the ageing process by contributing beneficial factors, factors that would help maintain and repair any damage that occurred in cells, such as vitamins, which the body cannot synthesise itself, but which the body needs to take up in the diet. It can also contain damaging factors that add to the problem rather, so, for example, if you have an unhealthy diet that is rich is sugar and saturated fat, it is known that this can increase the burden of cells with regards to oxiditive damage.
How is your research beneficial in terms of old people's health?
We hope very much that the work we are doing in basic biogerentology - that is to understand basic molecular mechanisms operating in every cell that lead to the process of ageing - will contribute to an improved quality of life for the elderly. We assume that many ageing associated diseases, like cardiovascular disease, Alzheimer's disease, cancer and many others, result from deficiencies, perhaps just subtle deficiencies, in the body maintenance and repair functions. Therefore, if we manage to understand these maintenance and repair functions, if we can detect early on any deficiency in such functions, perhaps in specific organs, then we have a chance for intervention to correct the deficiency if possible, so allowing the individual to live to his or her full potential life span.
Professor Anthea Tinker - a social gerontologist, whose research interests include the social issues relating to old age. Professor Tinker believes that the quality of life is at least as important as its quantity. Important social and economic issues need to be addressed if an increasing elderly population are to lead happy and fulfilling lives.
What do elderly people want from current research into ageing?
I think the research into ageing and its biological aspects is extremely important. But what most older people want is basic services and of course it's the little things in life that often make such a difference to them. Research into things like arthritis or incontinence are equally, if not more important - the point is the quality of life. Ten years ago I was in a television show with an audience of about 50 or 60 older people who were asked to put up their hands if they'd like to live to one hundred. Only two people put their hands up - one because she wanted to see a great-grandchild born and the other one just wanted to pay off the mortgage.
What are the implications of increasing the number of older people in society?
If we do have many more older people and fewer younger people we have got to have a radical rethink in society. I think the first thing is about employment - many older people would actually like to continue working, perhaps part-time, so I think the idea of people retiring early is probably going to go out of the window, and so we will have more people in paid work. There are also implications for society as well, I think we may tend to value old people and their contribution more- I'm thinking particularly if women are going to go out to work as well as men and therefore grandparents are going to be needed for childcare.
There's also undoubtedly a lot of evidence about age discrimination and prejudice in the health service and in society as a whole, because we are very much a youth dominated culture. I think that's going to have to change and I'm sure it will, because the more older people we get, the more articulate and vociferous, and we're probably going to copy the Grey Panthers in the States, or we've seen the rise of older people in the Netherlands, for example, where they're actually having an imprint on design.
So I think older people are going to become much more important and of course a much larger proportion of consumers market, and if you've got buying power you're important. There are also going to be implications for housing, there will be more needed, partly because there'll be more older people, partly because more people are living alone, and the younger people who are living alone now in middle age are probably going to continue to do that. We're also going to need much more friendly designs.
How likely is it that we will all live to be 100?
The number of centenarians is on the rise: in 1951 there were 300, there are currently about 6,000, but in 2036 there will be 40,000. So a number of us will live to be 100, but certainly not millions.
Is the possibility of living increasingly longer a positive development?
As long as the biological research is going to allow older people to live healthy and fulfilling lives, that's fine, but we also have to think about the social implications and the quality of their lives, which is not only to do with biology, but it's also to do with their social relationships and their surroundings. For example, if people are going to be married for 60 or 70 years to the same person, what effect will that have on them?
Dr John Sinden - chief scientific officer at ReNeuron Ltd, a company researching stem cells and possibilities for reversing cell damage in the brain. ReNeuron's work has demonstrated that injecting stem cells into the brains of mice can reverse the effects of stroke.
Could you explain a little about your company and the research that you do?
ReNeuron is a company in Guildford in Surrey, set up originally in King's College in London. It is based on the technology of generating neural stem cell lines that could be developed as products for treating major neurodegenerative diseases, particularly those in the elderly.
What are stem cells?
Stem cells are the first product of conception, so sperm meets egg, generates initially a single cell then a ball of cells, and then you have the beginnings of a human being. So stem cells are the early cells that are constantly dividing and gradually throwing off cells that are going to make up our bodies, our brains. The important thing is not only are they important in the whole process of development, it appears that their nature is a regenerative cell, so they are capable throughout life of regenerating all of our tissues, by actually inducing our natural cells to become alive again if there's any damage that occurs.
How did ReNeuron come about?
Well, we started with a stem cell line that we generated from mice, and we used it as a source of cells for transplantation purposes for animals that had a specific kind of damage. We injected the stem cell line near to the damage and what surprised us is that the cells actually migrated into the area of damage and when they got there they differentiated, that is, they made the right kind of cell that was missing in the brains of those animals. That was an important discovery because nobody had ever shown that before with any tissue system. So we were able to patent that then set up a company which was really directed at developing stem cell lines that could be available, as it were, off the shelf to neurosurgeons or to surgeons for the purposes of injecting into patients that had suffered some kind of damage.
Could you describe further what your research has discovered?
If you take the example of a stroke, it is a massive amount of damage on one side of the brain. What we've found is that if we take one of our stem cell lines and we inject it, we can even inject it on the opposite side of the brain to where the damage is, the cells actually cross over on the telephone exchange that connects the 2 sides of the brain, move into the damaged area and make new cells that are typical in the region that where the damage is. But they also act along with a process that seems to be naturally occurring within the stroke brain. There seems to be a natural attempt by the brain after a stroke to try and send out signals, to try and recover itself, and we've actually identified a marker for this process, a marker known as an 'apolypoprotein'. What we've seen that there's more of this marker in the rats that have had the stem cell graft, indicating that the cells themselves are participating in this active process of regeneration.
Is there a potential risk to patients of the stem cells going out of control once they've been transplanted?
What we're doing is generating a cell line that is a homogenous cell line, that we can test thoroughly prior to it going into the clinic, so it can be tested in the lab, it can be tested on animals, and then subsequently also be tested on a small patients groups in clinical trials. Clearly those cells are homogenous, they will not continue to grow once they've been transplanted, so there's no risk that the graft will overgrow and generate side effects.
How is your research applicable to treating age-related diseases?
Stem cells are actually with us throughout life, so literally they're the first things that we have that make us up, but also they persist, to a greater or lesser extent. But as we age we gradually lose our stem cells, because they're used up to repair a bit of damage here, to patch up a bit of damage there, and as we get older we have no stem cells within us that are able to repair any serious form of damage such as a stroke. However, it's almost certain now that our brain retains the capacity to deal with stem cells so if we inject them into our brains the signals are present to direct those stem cells to make the cells that have been lost in brain damage.
How will people benefit from the research that you are doing, and how soon will it be before these benefits are apparent?
The diseases that really prove to be the major drain on resources, both within the health service and with the social services, are the major degenerative diseases of the elderly, and the best examples of these are obviously stroke, Alzheimer's disease and Parkinson's disease. There are no really effective treatments for these conditions, particularly in the case where patients have had these diseases for a certain period of time - there are often some drugs that can be used in the early stages of the diseases, but these have a relatively limited life span in terms of keeping the patients well and retaining their independence.
What ReNeuron is seeking to do is to generate a variety of products that can be used where there are simply no other drugs available, that is in patients that have had these diseases for a length of time, where they're showing chronic disability, where their prognosis is poor. Here we can offer at least the hope that these patients would retain their independence and not be dependent entirely on the State or on the hospital system for their life.
Our first target is stroke, because there's a huge incidence of stroke in the elderly every year, most of the patients will survive that stroke and most of those patients that survive will have a chronic disability - inability to speak, inability to move an arm, to walk properly - and they will be seeking something that will help them. Our first cell line that we're developing now is a human cell line from the region of the brain that's affected in stroke, and we're actually selecting that cell line to go into banking at the moment. Certainly what we're talking about here is small scale trials, and there will be a long process that the regulators - the government agencies that approve the widespread use of medicine - will be involved in. Clearly it will take some time to convince them that this really very novel form of therapy is both safe and efficacious. So we don't expect that a product will be widely available for some years, and we're obviously going to be increasing the number of products that we hope to have available, so we're looking at products for Alzheimer's disease and Parkinson's disease as well.
We are also looking at different types of diseases that we believe would be amenable to stem cell therapy, including heart disease, where heart attack is obviously a major killer and the actual damage to the heart we believe could be repaired by a simple injection of stem cells. I think it's important to remember that this is a treatment that has not yet been used in human patients - the next major milestone in stem cell research is going to be testing the stem cells in humans. I think, nevertheless, companies like ourselves and scientists like myself are very confident that this is something that will move forward quite fast and once the initial proof of principle has been shown in humans then really the whole world is going to open up for a whole new set of treatments.
Dr David Gems - a geneticist at University College London who has increased the lifespan of nematode worms by up to three times. He is investigating the genes which are responsible for this, many of which have human 'homologues'.
What do you hope to achieve through your work in understanding the ageing process?
What we know about ageing is that it's caused by genes - different species of animals have different life spans and the reason for that is that their genes are different. So I might live to be 80 and the worms that I work on die after about only 2/3 weeks. What we're trying to do is identify in worms the genes that control their life span, and then perhaps we can find the human equivalent and understand something about human nature.
How do you go about doing this? What have you found so far?
The way that we try to identify genes that control ageing is to look for animals which live longer because they've got something wrong with one of their genes. We've found strains that live much, much longer than normal because a particular gene has been changed. So, for example, if you change a particular gene called Daf 2 you can you can increase their life span by up to about 200% - for us that would be like living to be about 250 years old. What's really interesting is that this gene that controls ageing in worms has an equivalent in human beings, but what we don't know is whether the human equivalent of this gene is controlling human ageing.
What have you found out about the effects of calorie restriction on the ageing process?
Calorie restriction has been known about for a long time. If you take a laboratory rat and you reduce its calorie intake a certain amount, you can increase its life span by up to about 50%. The reason why life span is extended by calorie restriction may be something to do with evolution, it may be that in the wild when there's no food around animals have this way of adapting, reducing their fertility and slowing their rate of ageing. One thing we can say about calorie restriction is that it seems to work in all animals that have been looked at. There are trials at moment taking place in Rhesus monkeys and although it'll be a long time before we know the answer, they appear to be responding in the usual way, their ageing seems to be slower. So if calorie restriction seems to be working monkeys, the chances are that it would in principle work in us.
So we could eat less to live longer?
Unfortunately, if you want calorie restriction to work you have to reduce your calorie intake by about 40%, which is just near starvation levels. People have tried it and it's a very miserable life, you're hungry all the time and it's really not worth the pain for the gain. But there is the possibility that this group of genes that we've identified that controls ageing in worms - the Daf 2 genes - are actually the genes of calorie restriction, so maybe by understanding these genes we can understand how calorie restriction works and reduce the rate of ageing without having to reduce calories themselves.
How close are we to understanding and being able to affect the ageing process?
As far as really understanding ageing goes, I'm afraid that we're really at the beginning of a long road, but at least we are at last on the road. In the short term I think there's one thing that we may be able to understand, which is the way that animals can change their rate of ageing in response to diet, so that potentially could lead to therapies that might slow down human ageing to a degree. But I don't think that you'd be talking about anything more than adding a few decades to life. Those are things that in principle might be possible through hormone treatments and through drug treatments, but as far as anything more profound goes, as far as, for example, slowing ageing until it stops, curing ageing or anything of this sort, frankly I doubt whether that will ever be possible, at least by means of drugs or hormone therapies. I think to achieve that might be possible if you resorted to genetic engineering and actually altering the human genome - you'd have to really radically change human biology to be able to slow ageing down so that people would live centuries.