Young at Heart - Healthy Ageing

28 September 2008
Presented by Ben Valsler, Helen Scales.

This week, how to live longer and look younger with the science of ageing! We discover how repairing damage to DNA could prevent the diseases associated with old age, and find out how to keep your skin looking younger for longer. Also, doing just four things could add fourteen years to your life - so find out what they are, right here! Plus, how gene therapy could cure one from of blindness, how to get more distance from a tank of diesel and counting insects - how bees can count up to four, but not five. Also, in Kitchen Science, we explore the stretchy science of rubber bands!

In this episode

Heat Shrink! - Why rubber bands get shorter when you heat them.

19:47 - Damaged DNA

DNA damage leads to many of the diseases we associate with ageing, so if we could stop DNA from being damaged, or repair existing damage - could we stay young forever?

Damaged DNA
with Steve Jackson, Gurdon Institute, University of Cambridge

Helen - Why don't we feel as young as our youngest cells? The answer could be the damage to our DNA due to exposure to radiation or toxins or just the copying errors when our DNA is replicated. Professor Steve Jackson joins us now from the Gurdon Institute here in Cambridge University. His team are trying to understand better how DNA becomes damaged, how this damage relates to disease and how to repair damaged genes. Hi Steve, thanks for coming on the Naked Scientists.

Steve - Hi

Helen - So how does DNA become damaged in the first place?

DNASteve - There are a tremendous number of ways that DNA can become damaged. We are all aware of the fact that if you sit in the sun too long the ultraviolet light can damage DNA, so chemicals can. Radiation use, for example in radiotherapy, can damage DNA. Actually the largest source of DNA damage is oxygen. About 2% of the oxygen we breathe actually gets converted into things called reactive oxygen species in the mitochondria in our cells. Some of that escapes. That, together with hydrolytic reactions catalysed by water are occurring all of the time in our cells, even if we are sitting in the dark away from everything else and not being exposed to any chemicals. The amazing thing is that we have around 1014 cells in our bodies and every cell in our body is sustaining around 100,000 lesions per day. Our bodies, even if you're not sitting in the sun and you're not exposing yourself to any other chemicals, are having to deal with somewhere in the region of 1018 to 1019 lesions per day.

Helen - Is that lesions in the DNA?

Steve - That's damage to DNA, yes.

Helen - So our DNA is being damaged all the time, but why does this now lead to disease?

Steve - Well, fortunately the vast majority of that DNA damage gets detected very rapidly by certain specialised proteins in our cells and gets repaired. So the vast majority of that DNA is repaired. Some of it isn't, it escapes these surveillance pathways. That damaged DNA, when it eventually is put back together again, often has errors which are mutations. Those mutations can mean that the cell isn't working in the way that it should.

Helen - You mentioned the surveillance, now this sounds like there is something fantastic going on in our bodies to try and undo this damage that is happening to us on a daily basis. So how can we actually repair our own DNA, what's going on inside the cells?

Steve - Well if we didn't have these surveillance pathways we wouldn't last very long. The fact is that most of the DNA damage that is occurring is repaired. What my lab and other labs in this area are working on is trying to understand how these "molecular policemen" work. Really they are molecular policemen that patrol the cell looking around for damage, not doing very much, but when they stumble across damage, as it is occurring all the time, they jump on the DNA. They then send out signals for the cell, alert signals for the cell to stop doing things such as dividing while the damage is there, then hopefully repairing that DNA damage in a way that doesn't generate mutations. These pathways work very well but occasionally they go wrong and that can lead to mutations that can contribute to diseases such as cancer and we believe it can also contribute to ageing.

Helen - You touched on the idea that we might be able to do something like use these mechanisms of repair ourselves and actually promote that kind of repair. Is that something that we're actually seeing happening already or are these just still ideas to mimic those actual repair mechanisms?

Steve - I think ultimately it should be possible to find ways of improving these surveillance/repair mechanisms. If we could find ways of improving them I would place a bet that it would slow down at least some aspects of ageing, maybe not all of them. The problem is that our cells are working very efficiently already so trying to find a way to make them work even better is difficult. One very interesting idea is that many pathways, just like the police forces or other surveillance systems, can work in a latent capacity or can be induced. There is a growing body of data now showing that a little bit of stress to the cellular systems can hyper-activate these repair pathways. So I think one of the major opportunities might be finding ways of boosting our defence systems by making ourselves in this higher state of alert. If we could do that or find drugs or other ways of bringing that about then that might actually slow down ageing at a cellular level.

Helen - So if we could tease ourselves into thinking there is a little bit of damage going on perhaps, or mimic that, then the cells might actually kick in that repair mechanism and help repair the damage to the DNA.

Steve - Absolutely. I think even some things that we know might contribute to slowing down ageing, at least in some regards, such as exercise, might be exerting some of their influences by stressing our cells and we know that stress tends to induce these repair and other pathways.

Helen - So a little bit of stress might be good for us.

Steve - That's what I keep saying to my students.

Helen - So do you think we could ever stop ageing altogether, or is this something that is such an inherent part of life that we're never going to overcome the fact that DNA suffers so much damage as we live our daily lives?

Steve - I think it will be very difficult to find ways of reversing age, or even stopping it. As I pointed out earlier on, much of the DNA damaging chemicals, such as oxygen and water, are intrinsic to life. It's very difficult to have a system that is 100% accurate in terms of repairing damage. Having said that we know that different mammals can live tremendously different lengths of time so it is possible for an organism to develop in a way over evolution to live much longer or live less long. I think if we understand all these pathways and also understand why some organisms live longer than others we may be able to find ways of tweaking the system to make us live longer.

Helen - If it isn't just a case of living longer but perhaps improving certain parts of our lives. Is there anything in particular that damage DNA - apart from diseases - are there any other aspects that we can work at improving through maybe mimicking these repair mechanisms? Are there other aspects of ageing in the body that are really the crucial things that we would want to look at?

Steve - I think it's very easy to think about ageing as a superficial thing such as the greying of your hair or the wrinkling of your skin. The reality is the ageing has a range of diseases associated with it. That includes neuro-degeneration, cardio vascular disease and cancer. We know from working with a number of labs including ours that defects, or problems with these DNA repair mechanisms, can lead to cancer. We also know that they can lead to neuro-degenerative disease and there is growing data suggesting it can contribute to cardiovascular disease. So I think ageing shouldn't be thought of as a superficial issue. Ageing occurs in our organs and our brains and I think these are the kind of diseases that we might be thinking about alleviating

Helen - Thanks Steve, that's Professor Steve Jackson from Cambridge University explaining how stopping DNA from getting damaged could lead to longer, healthier lives.

27:01 - Younger-looking Skin

Meera finds out how to keep your skin looking young and healthy...

Younger-looking Skin
with Patrick Bowler, British Association of Cosmetic Doctors

Meera - Whilst ageing is both a physical and psychological process, when many of us think about getting older we think of wrinkly sagging skin. So this week, I'm in Brentford in Essex in the home of Dr Patrick Bowler, fellow of the British Association of Cosmetic Doctors, to find out what happens to our skin as we age and if, as all the cosmetic companies promise, it's possible to reverse the effects of ageing.

Patrick - The skin is the largest organ in our body. We have a base layer, called the dermis, in which there are blood vessels and fat and nerves. Then there is a very important layer above that - the epidermis - which produces new skin cells constantly. These cells make their way to the surface and shed off in a 28 day cycle, or something like that.

Meera - So what happens to our skin as we age?

Patrick - There are many factors that cause our skin to age. There is a genetic factor, then there are environmental factors which are probably the most important. There are a number of changes that go on in the skin. The skin becomes thinner so if you took the extreme of a lady in her eighties or nineties and looked at the back of her hand the skin is almost translucent and you can see the blood vessels. We get pigment changes, age spots and the elastic tissue, a bit like the cement between bricks, and the foundation of the skin starts to reduce in strength. That is part of the problem in developing sagging skin and wrinkles. So the supporting structure of the skin starts to become less elastic.

Meera - I can imagine that a loss of elasticity can cause sagging, as the skin is less taught. What about the wrinkles, why do they happen?

Patrick - There are different types of wrinkles. If you look at the forehead for example or around the eyes where there is a lot of muscular movement. The muscular movement plus damaged, aged skin produces wrinkles. As we go further down the face to for example the cheeks and down into the jaw line and the neck, that is more due to loss of volume in the skin so you lose fat and elastic tissue and we therefore get sagging. In that sagging you get wrinkles. It's a bit like letting a balloon down quickly; you're left with that crinkly appearance

Meera - In our society today there is a wide range of products out there that people are resorting to in order to try and reverse these effects. What are these ingredients that are being used in the creams that are purely targeting people that are wanting to reverse their ageing?

Patrick - We had about 25 years ago a big breakthrough in skin treatments, where a form of vitamin A called a retinoid was actually shown to reverse some of the signs of ageing. That's pretty miraculous for that to be proven scientifically. It was in a very strong form of vitamin A which was quite irritating. At that time the cosmetic companies jumped up and down and thought that this was fantastic and that they would use this. They developed ingredients derived from vitamin A which are basically different types. Most of them are weak because if they increased the concentration then they would become irritating. Unfortunately you have to increase the concentration for them to be effective and a true anti-ageing effect. All the vitamins you see in over the counter products, like vitamin A, C and E (which are the common ones that we see) are going to have a positive effect, but are not going to be true anti ageing effects.

Meera - So, is the true way to have an anti-ageing effect then, to irritate the skin and then cause the skin to regenerate?

Patrick - With vitamin A, that is the case. The concept of irritating the skin on the surface makes the cells underneath react and produce newer fresher looking skin cells. In a single skin cell, and this always amazes me, there are something like 10,000 receptor for vitamin A. When vitamin A locks onto these receptors, certain things trigger off in the skin which affects cell division and other complex chemical cycles that go on. The vitamin A, retinoids in particular, have also been shown to stimulate collagen production in the dermis. This is very important because one of the effects of ageing skin is that we lose collagen and volume. So if we replace that in some way that is going to have a true anti-ageing effect. In summary it is not just the irritation: there are some more profound things going on deeper in the skin and in the cells that we don't really understand just yet.

Meera - What if people were to just increase vitamin A in their diet rather than applying it to their skin?

Patrick - Vitamin A, in particular if you take it orally can be toxic if you over do it. It can have quite serious effects on the liver. So I would usually advise my patients in this instance that it is good to treat the skin inside and out. So apply creams containing vitamins superficially and also ensure you have an adequate diet. If you don't think you do have an adequate diet then take a vitamin tablet as a fail-safe.

Meera - What should people be doing in order to help their skin in the long-term and just try to not maybe resort to cream?

Patrick - For most things moderation is the key. However looking after your skin there is one thing that is really important. You have to be very careful with the amount of sun exposure you have. To have in your moisturiser a sunscreen is probably the best tip that I can give you to keep your skin looking good.

33:30 - How to Live Longer

You may be surprised to hear that some very simple lifestyle changes can extend your life by 14 years! We find out how to live longer...

How to Live Longer
with Nick Wareham, MRC's Epidemiology Unit, Addenbrooke's Hospital

Ben - Professor Nick Wareham joins us now. He's the director of the MRC's Epidemiology Unit at Addenbrooke's Hospital. He's been part of the European Prospective Investigation of Cancer study, better known as EPIC. In January this year they announced there are four simple things you can do to extend your life by an estimated 14 years. Nick, thank you for joining us. What are these four things that people can do and why do they have such a large impact on how long we live?

Nick - They're smoking, drinking in moderation, not being totally sedentary (so having sufficient physical activity) and eating a diet that's rich in fresh fruit and vegetables.

Van GoghBen - I guess when you say smoking you mean not smoking?

Nick - Not smoking, yes! Absolutely.

Ben - Why do they have such a big impact?

Nick - Well, they are risk factors for a whole range of chronic diseases and indeed many of the diseases that you were talking about earlier to Steve: cancer, cardiovascular disease. These are the diseases that really shorten our lives and for which we have evidence that shortening is modifiable. In the study you're referring to this is observational data. It's not an experiment. We haven't had a group of people who we've randomised to be smokers or non-smokers. These are observations in a very big population study but they are robust. Really, what was surprising about the observation was not the fact that smoking and drinking too much are bad for you. It's really the magnitude and it's the scale of the effect on longevity that we observe.

Ben - These are obviously very difficult things to study. You have to rely on people being honest. Obviously if you've got a secret smoker he could squiff your data completely. How do you try and look at all these different lifestyle effects? It's obviously difficult to say these people are healthier - it's easier to say these people lived longer. How do you pull all this data together?

Nick - What you have to do is you collect a very big cohort. A cohort is a population of people who you recruit at baseline. You hope that they're free of disease at that point. You ask them questions or you may monitor different behaviours. Then you wait because the key thing is elapsed time. Over time some people go on to get particular diseases and some people unfortunately die. In the study that we reported earlier this year we started out with a cohort of 25,000 people in Norfolk who'd helped us in the beginning of the 1990s and who were then followed up to see who would get a disease. Really what the essence of epidemiology is that scale, very big studies; and then probability. Whether or not someone goes on to get disease is a process that involves an element of chance. Clearly some people have certain lifestyles and do very well. Some people have the same lifestyle and do very badly but on average one can estimate the probability an event will occur. That's what you do in epidemiology.

Ben - So epidemiology's obviously quite a powerful technique but a lot of people would say based on their personal experience or anecdotal evidence, 'My uncle smoked and drank a bottle of whisky every week and lived to 108.' Are these people taken account of or do you try and go for the common denominator? Are you looking at the average or are you looking at the normal?

Nick - We're looking at everybody. So for everybody who's got an uncle Tom there's probably a equivalent number of people who have an uncle Frank who might have lived and exemplary lifetime in terms of the behaviours we've talked about but was cut short by a disease. One's looking at average probability. Unfortunately most people tend to remember the anecdotes that are an excuse for unfavourable lifestyles.

Ben - One of the things you've been working on is how activity in earlier life affects things like type 2 diabetes or other diseases associated with age. What have you found so far?

Nick - Physical activity is probably a very powerful determinant of many of the diseases that we're seeing rising today. This is clearly a major factor of why as a population we're tending to get more overweight. Overweight by itself is the single biggest determinant of type 2 diabetes. We operate in terms of what's called relative risk in our game. That's comparing the risk of a disorder in one group compared to a comparison group. If you were to take obesity as a risk factor the relative risk of something like 60 for someone who is overweight compared to someone who is normal weight for type 2 diabetes. It's very, very strong. One of the reasons we focus on that is in part because it's an important factor but in part because it's relatively easy to measure. The problem about physical activity is it's incredibly difficult to measure and we rely on self-report. We ask people about their physical activity. The bit of activity that people can remember is that part that usually involves putting on lycra or going to a gym or something very specific and circumscribed like that. In fact what we're finding is that part is important but that part doesn't actually occupy much of our life. Most of us spend most of our energy in a rather insensible way just walking around or standing running and sitting. We've been developing techniques for studying that aspect of activity. It seems that part is really important for determining obesity and diabetes risk. The importance of that is not just as an observation but what it says about what you should do about the problem. Promoting sport and encouraging exercise is absolutely critical. In a population we probably need to also be thinking about whether we just encourage people in an insensible way to waste more energy. That means re-engineering society, putting staircases in more prominent positions, perhaps moving escalators or lifts. Things like that.

Ben - Epidemiology is a good tool for forming policy if you can say these sorts of things. What do you think we should do to try and make our population age more healthily?

Nick - I think we should clearly focus on those four behaviours. There's four critical public health targets and I think we've made progress amongst adults smoking. What's discouraging is the number of children and adolescents who are taking up smoking. If smoking gives rise to hundreds of thousands of deaths per annum unfortunately the smoking has to recruit that number of people just to keep that business stable. I think focussing on the smoking message on people starting is as important a public health issue as trying to help people stop. Clearly there's been a big furore recently about the moderating alcohol consumption and that is something that's going up. There's a public health issue. Fruit and vegetable intake: there are clearly the five-a-day messages and we should stick to those and try and do our best. Physical activity: in our study the risk group was actually totally sedentary. They had a sedentary job and were doing nothing in their everyday lives in terms of leisure time activity.

Ben - Your traditional couch potato?

Nick - Yes. That and I guess the message here is that the public health recommendation which is to do 30 minutes five times a week is a long way from some people's reality. I think there's an alternative message which is actually just do some more because there are benefits to doing something other than nothing.

Ben - Even things like hovering, which I've been told actually burns quite a lot of calories.

Nick - Hoovering, yep. Especially amongst men!

Ben - DIY too.

Nick - DIY, anything you can. Actually DIY is  - we all sit for most of our jobs and there's a very interesting recent study about the time spent sitting and its relationship to diabetes risk. If we've got a sedentary job there's maybe not much we can do about the total duration of sitting. In the same study what they looked at was if you break that sedentary time but overall the sedentary time as a totality is the same, people who had more breaks in the sedentary time, had a lower risk. I think there may be some important messages there about getting up from our desks and our computers periodically. I would argue it's probably good for concentration. It would be very interesting if it was actually also good for our physical health.

Ben - You said that drinking was going up at the moment. Is it likely that we are storing up problems for the next generation? Are today's adolescents going to be even more disease-prone than today's pensioners?

Nick - That is the six million dollar question. This is really the problem that we face in public health. We always used the past to predict the future. The cohorts that we have now, on which we're basing our information about risk, studies like EPIC, those studies recruited people maybe 20-30 years ago when the risk factors were as they were then and medical care was different. The issue is what are the current generation going to face in the future? We don't know. All we can do is say we know that obesity and other risk factors are incredibly important. Based on our observations from the past we would say that the current generation, if they don't take some action, are going to have problems with their metabolic health in particular.

How do our cells know how old they are?

Steve - First of all, some cells in our body don't divide such as nerve cells and so they really aren't. They last our whole lives but even the cells that do turn over- a new cell is generated from the division of an existing cell. The age of an existing cell basically gets transferred. The new cell remembers how old the other cell was. One of the important things that is transferred are the chromosomes. The ends of the chromosomes - called telomeres - get shorter every time a cell divides. They are a very useful counting mechanism. These telomeres shortening is one of the important counting mechanisms that tells our cells how many times they've divided and how old they are.

Why does hair lighten in the Sun?

Ben - This is basically because hair is dead. Once it comes out of you, once it's grown, all the melanin it will ever have has already been put into it. It gets broken down by the sun but in your skin the melanin gets replaced when melanocytes put new melanin into your skin.

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