Dodging Death: Growing Old in Good Health
How can we stay sharp as a senior citizen? This week, we explore the different biological approaches to understanding healthy ageing, discover a protein that may prevents age-related nerve degeneration and find out how to preserve cognitive function as we age. Plus, why Eunuchs lived longer, and how to turn trousers into catalytic converters that filter polluted air!
In this episode
01:08 - Ageing and Bioscience at the Babraham Institute
Ageing and Bioscience at the Babraham Institute
with Linda Partridge, Institute of Healthy Ageing at UCL, Tom Misteli, National Cancer Institute in Maryland, Jan van Deursen, Mayo Clinic in Rochester, Minnesota
Understanding age and age related diseases involves research at every level - from populations through individuals, their organs and separate cells, and even down to the molecular domain. These approaches were brought together recently for conference on Ageing and Bioscience, hosted by the Babraham Institute just outside Cambridge. And despite their different scientific backgrounds, researchers of age and age-related diseases appreciate that it's not a purely academic problem they face.
Linda - I'm Linda Partridge and I'm Director of the Institute of Healthy Ageing at UCL. A very practical problem, I think, is the one that many of us are trying to address, which is how to keep people healthy as they get older. The economic impact of the ageing population on health services is just becoming completely unmanageable. There have been a lot of headlines recently about the National Health Service and the very complex presentations that are coming in with a lot of old people and really, the inability of the system to cope. And of course, the major burden of ill-health is falling on older people now, so that's where we should be focusing our attention to try and help people.
Ginny - Some people, of course, live longer than others. In some cases, much longer. So can we just look to them to understand how to live long healthy lives?
Linda - One of the most interesting facts is that people who live to be over 100 (centenarians) are terribly average in the way that they behave. They're no less likely to smoke than other people. In fact, the world lifespan record holder was a French lady called Jeanne Louise Calment and she gave up smoking when she was 119. So clearly, these people must be very resistant to the effects. They're no more likely to take exercise, they're no less likely to be podgy than other people. They're a bit of a mystery really, but they do seem to have some genetic characteristics, which interestingly are similar to the ones that made laboratory animals long-lived. So, that's a rather nice ray of light that suggests that we really can use simpler animals that don't live as long as humans and where we can do experiments to try and understand the mechanisms of human ageing.
Ginny - Genes of people who live long healthy lives can only tell us a part of the story. For Tom Misteli, Associate Director at the National Cancer Institute in Maryland, the answers lie in a set of rare diseases.
Tom - One tool, one way to study human ageing is by looking at premature ageing diseases. So, these are very rare diseases, most of them, where people age prematurely very, very rapidly. There's about 6 or 7 of those that we know of and interestingly, all of those have something to do with DNA damage and DNA repair. The advantage that we have with these premature ageing patients is these are all genetic diseases, so we actually know exactly what is wrong at the DNA level in those patients. So for example, we work on a particularly rare disease, which is called Hutchinson-Gilford Progeria Syndrome. This disease is caused by a single mutation in the genome. We know exactly what the mutation does at the level of DNA, at the level of protein, and then we begin to study what happens at the level of cells. So, this particular mutation, for example, causes a defect in the cell nucleus, in the structure, in the architecture of the cell nucleus, and that influences the organisation of the genome and actually leads to DNA damage and subsequently to that then to the ageing defect.
Ginny - But can disordered ageing conditions really tell us about normal, healthy ageing?
Tom - I think the answer for all of these premature ageing diseases is, yes and no. So, there will be certain aspects of the disease which are also found in normal ageing and then other aspects are missing. So for example in our favourite disease, this HGPS disease, we see many, many of the phenotypes at the cellular level that we see in patients. We also see those in healthy, normally-aged individuals. The patients for example, they all die of cardiovascular defects, heart attacks, and stroke, and the pathology of those cardiovascular defects looks very, very similar to what you see in a normally-aged person. On the other hand, the patients that we're looking at for example, they never develop tumours. We actually find that interesting. We actually use that now to ask, "What are the mechanisms that prevent tumours or promote tumours in aged individuals?"
Ginny - The link between age and tumour growth prompted Jan van Deursen from the Mayo Clinic in Rochester, Minnesota to approach ageing from a perspective of cell biology...
Jan - Around the age of 45-50, chances of getting cancer increase exponentially. Cancer is considered to be a disease of gene mutations. They don't necessarily increase dramatically around that age and so, that doesn't really explain that acceleration. I think that we're missing something. We have a missing link. Perhaps that missing link is the changes in tissues that happen in general during the ageing process that become much more permissive for cancer cells or pre-cancerous lesions that we are all carrying to turn into tumours. So for instance, as we age, we accumulate more and more so-called senescent cells, which are aged cells. What these aged cells do is they secrete growth factors that stimulate tumour growth and then proteases that kind of chew up the tissue structure so that it's easier for cancer cells, once they are forming in a tissue to actually escape the tissue, and form a metastatic tumour which is usually what's killing people. So, that's the kind of hypothesis that is finding some traction right now.
Ginny - Senescent, or aged cells, create a tissue environment that encourages the growth of tumours and these cells are also known to cluster around the sites of damage in age-related diseases. So, could removing them slow ageing?
Jan - We have shown that if you clear senescent cells in an animal that's ageing - as they are formed, you get rid of them - you can attenuate a series of age-related pathologies. And so, the idea is, if you can find a drug that can mimic what we did through a genetic trick in the mouse that you might have benefits in the health span, so health span is the period of your life in which you're free of major chronic diseases. You know, we always talk about longevity, but nobody wants to live long if you're not healthy.
Ginny - We're beginning to develop an understanding of the genetic and cellular underpinnings of age and age-related diseases. But if we are to come up with a formula for a long and healthy life, we need to know more about our lifestyles and the environment in which we age. Linda Partridge's work at the Institute of Healthy Ageing is shedding some light on the role of diet and nutrition.
Linda - One of the obvious features of these pathways that can seemingly ameliorate the ageing process is that they're the ones that respond to diet, they detect nutrients, and they determine what the animal does in response. Can it afford to reproduce, mount an immune response, grow, that kind of thing. So, given that they are rather central control systems for matching food to activity, knocking down their activity can have quite a lot of side-effects and not desirable side-effects like impaired wound healing for instance. So I think the name of the game at the moment is trying to understand how these pathways can improve health during ageing and whether that can be triaged away from these undesirable side-effects that seem to come along with it. So, drilling down into these pathways, trying to find out what genes show altered activity, can we separate them out into groups that are controlled by different mechanisms, and just target the ones that improve health? I think the jury is out on that at the moment. We don't know if it's going to be possible, but there's every hope I think that it will be.
Ginny - Linda Partridge from UCL and before her, Jan van Deursen from Mayo Clinic and Tom Misteli from the National Cancer Institute.
09:50 - Why Senior Moments Are Not Inevitable
Why Senior Moments Are Not Inevitable
with Professor Lorraine Tyler, Cambridge Centre for Ageing and Neuroscience
Ben - On average in the western world, we live longer now than we have ever lived before. But a longer life doesn't necessarily mean a healthier life. So, lots of this scientific research in this area aims to increase not life span but actually increase health span.
It's quite well-known that even with normal healthy ageing, we do seem to see a decline in our cognitive functions over time - that's the ability with language, memory, attention, etc. - and the Cambridge's Centre for Ageing and Neuroscience or Cam-CAN was setup to try and understand how this happens and to find ways to extend our cognitive functions into old age.
We're joined by Professor Lorraine Tyler who heads up Cam-CAN. Lorraine, thank you ever so much for joining us. Is it a simple case that no matter what we do, we're going to lose cognitive function as we get old?
Lorraine - It's quite clearly not the case. One of the things that we do know is the variability in both the cognitive functions that decline and their rate of decline, and also the fact that lots of people show variability in the extent to which their cognitive functions decline. So, one of the things that we're trying to understand and that will be especially possible if we can make the Cam-CAN into a longitudinal study, is exactly what it is about those individuals who show preserved cognition across their life span.
Ben - So, when we're talking about cognitive decline - I mentioned language, memory and attention - what are we really talking about? What are the symptoms that we see?
Lorraine - Well, I think that lots of people would say that they see the effects of memory decline as they age. People think that they have problems with language when they have word-finding problems, but in fact, language comprehension remains intact throughout the life span. I mean, people can talk to each other and understand each other throughout their lives. Attention is supposed to wander, but I think the thing that people notice most of all is memory loss. This is not true for everyone and the other thing is that the extent to which we notice what we think of as being declines is affected very strongly indeed by our stereotypes of ageing.
Ben - So, if we expect that we are getting doddery, that we're having senior moments then we're actually more likely to at least see that in ourselves if not, others.
Lorraine - Absolutely, yes. Also, the negative stereotypes of ageing also affect our own physical health.
Ben - So, almost a placebo effect and because we expect to be losing our memory, we actually start to lose it.
Lorraine - Yes.
Ben - That's quite remarkable. But when do this sort of thing start to kick in? I understand some of it is actually something I should be worried about. I'm in my early 30s and already, I could be seeing a decline.
Lorraine - Well, I think that people more strongly notice declines after about 50, but I think that's to a certain extent because once again, we expect to see it. So, when younger people forget their keys, you know how forgetful younger people are, but we don't think that they're suffering age-related declines.
Ben - So, when we're actually talking about the decline that we do see, so when we have somebody who's come in with a sort of pathological decline to the point where it's become a hazard, do we see a certain pattern in brain activities or a brain basis for the decline that we do see?
Lorraine - We work on healthy ageing, so at the moment, we're not looking at pathological ageing and if we do make this a longitudinal study then we'll be able to uniquely chart the trajectory from a healthy to pathological ageing. But in terms of healthy ageing and people noticing declines, it depends on what it is. Most noticeably I think, people notice decline in their memory. That's the earliest thing that happens. This does not necessarily straightforwardly reflect brain changes which are happening throughout our lives. The changes that take place in the brain, the reduction of grey matter for example, the neurons in the brain, the cells, and the white matter tracts that connects cell assemblies, occur throughout our lives and at different rates.
Ben - We know that brain is actually quite plastic. It can adapt. If somebody loses use of a certain limb or part of their vision, we know actually the brain can adapt to make use of those neurons. So, it does seem a little bit odd that we would lose our cognitive ability.
Lorraine - Remember that I mentioned before that there's a lot of variability in the extent to which people lose or show decays in cognitive functions and one of the things that we know from a number of studies now is that, as you said, the brain remains plastic and this is revealed in studies using imaging techniques, which can show us how the brain is functioning as it is carrying out particular kinds of cognitive tests. And what we see is that good performance in older people is typically associated with enhanced activity in the brain and this is in the context of reduced neurons and white matter tracts. You see a greater uptake in activity in other regions of the brain than those regions which would've been activated in young people. And the argument is, and the evidence for it is, that this association between reduction in cells, in brain shrinkage, increases in activation, they're associated with preserved function.
Ben - So, are we in a position yet where we can say that in order to preserve this function, you need to do a certain set of things? I know there's been research recently that showed that older people with a more active and larger social network for example were more likely to live longer and retain their abilities for longer. Is that the sort of advice we need to be looking at?
Lorraine - Yes, I think that's certainly one thing. Another thing for which we perhaps have the strongest evidence at the moment is exercise - cardiovascular exercise. There's quite a lot of evidence at the moment. It's not watertight, but it's emerging evidence that increased cardiovascular exercise helps to improve cognition, and there's also evidence that it's associated with neurogenesis - the formation of new neurons in the brain.
Ben - And anecdotally, we're told that if you make sure you keep doing your crosswords or perhaps learn a new language when you retire, these sort of things can also make sure that we retain those abilities later in life.
Lorraine - Yeah, I think there's less strong evidence for cognitive training effects, but I certainly think if it was me, well, I mean, it is me, I like doing crosswords and Sudoku and things like that, and I think one should set one's self challenges and try to get out of one's comfort zone.
Ben - Well, they do say that you never improve if you don't get out of your comfort zone.
Lorraine - Absolutely.
16:59 - Long-lived eunuchs
Eunuchs - men who were castrated as children - live up to 19 years longer than intact males, according to research by scientists in South Korea...
This study, published in Current Biology, was conducted using historical records of more than 385 eunuchs who lived in Korea - where they served the royal family - between 1551 and 1861.
From these records, Kyung-Jin Min and his colleagues at Inha University were able to find the dates when 81 of the listed eunuchs were born and died. They found that on average, each lived about 70 years, which is considerably longer than the 50-55 years managed by the equivalent intact man living at the same time. Ironically, this is also far longer than the kings they were serving, who managed, on average, just 47 years!
The researchers argue that this difference is likely to be down to hormone levels. Testosterone is mainly produced in the testes, so after castration the amount secreted into the bloodstream falls dramatically.
Testosterone might have a negative effect on the immune system, meaning the Eunchs were better protected against infection. It also causes aggression and competitive behaviour in humans and other animals, so it could be that these eunuchs were getting into fewer fights than their un-castrated counterparts and lived less stressful lives.
As well as living longer on average, eunuchs were more likely to live to be centenarians; in fact, there were three amongst the 81 individuals the scientists studied.
Compared with Japan, where centenarians occur at roughly the rate of one in every 3500 individuals, that makes the Korean eunuchs over 130 times more likely to be a centenarian than average - so there does seem to be something in the idea that reducing testosterone increases lifespan.
But we still don't know exactly how this happens, or whether only castration during childhood has the same longevity-enhancing effects. Would a man castrated later in life gain the same advantages? We just don't know.Some critics of the study have also pointed out that no difference in longevity is found when castratos versus non-castrato singers from the same era are compared.
A lot more research is needed before we can say for sure that castration will increase your chances of living to 100!
20:26 - Catalytic Clothing Cleans Polluted Air
Catalytic Clothing Cleans Polluted Air
with Professor Tony Ryan, University of Sheffield
Ben - Laundry detergent containing a special additive could convert clothes into pollution-busting air filters according to research funded by the EPSRC. The additive called CatClo stems from a collaboration between the University of Sheffield and the London College of Fashion. It's based on using nanoparticles of titanium dioxide to catalyse reactions that then break down the pollutants. Professor Tony Ryan, Pro-Vice Chancellor for the Faculty of Science at the University of Sheffield explained how the idea came about.
Tony - The problem was posed by a teenage girl and the teenage girl asked me a question about, "Can we use ambient energy to do environmental clean-up?" And it made me think about using the temperature difference between your body and the air, and there wasn't much there, and it just led me to photocatalysis. So, I realised that people are wandering around in the light, can we make light drive a reaction that does some environmental clean-up?
Ben - Titanium dioxide is also known as titania and is widely used as a white pigment in products as varied as paints and paper, through to foods, tablets, and even toothpaste. But it's another property, the ability to catalyse reactions in the presence of light that allows it to purge pollution.
Tony - The nano-titania has a very high surface area per unit mass. The reaction takes place on the surface. A photon comes in and excites an electron in the titania, that then reacts with oxygen to split oxygen into free radicals. Those free radicals react with water to make peroxide which is bleach and then that bleach oxidises things and it oxidises whatever it comes in contact with. Because it's in the gas phase, the things that get oxidised first and foremost are in the gas phase and so, they will be volatile organics, your smell, and any airborne pollutant. If you're in an urban environment then the concentration of nitric oxide is such that it will take out some of the nitric oxide.
Ben - Photocatalysis is not a new concept. Similar chemistry also using titanium dioxide is involved in self-cleaning glass.
Tony - The breakthrough, if there was a breakthrough was the realisation that the surface of a piece of self-cleaning glass is basically the length of the square of glass squared. Whereas your clothes, the surface area of your clothes is the surface area of all of the fibres, so it's much, much bigger than the area of the fabric if you were to unfold all the fibres. My suit has an active surface area of getting on for 60 square metres. Clothing tends to be at the level where you want to eradicate the pollution. You take advantage of the temperature gradient inside and out because that gives you a net flux of air and the environmental clean-up agent is perambulating. Even if you have an architectural surface covered with paint that is designed to take out air pollution, you still need the wind and not wanting to make a pun, people make their own wind.
Ben - But how much difference could catalytic trousers really make?
Tony - A pair of catalysed jeans will take out somewhere between a gram and 2 grams of nitric oxide out of the atmosphere a day. If enough people do that, the numbers build up very, very quickly. So for example, if half of the population of Sheffield were wearing catalysed jeans, we'd be able to bring Sheffield from exceeding the safe limit of nitric oxide which is 40 milligrams per cubic metre, and currently, we exceed it by about 10%, and it would be able to bring us below that value for the whole of the year in the city.
Ben - So, a fully catalysed person could make a minor difference, but reaching enough people requires a new approach.
Tony - In order for this to work, it has to be universal because the amount that any one person takes out is rather small. So, to take out the nitric oxide pollution from a single car needs about 5 people to be catalysed. So, what you need to do then is make sure that as many people as possible in a city are catalysed and rather than dealing with a brand of clothing, it's much easier to deal with something that everybody does which is wash their clothes. What we're trying to do is get laundry manufacturers to come together to deliver this technology via the laundry.
Ben - Of course, anything added to laundry detergent is going to end up in the sewers, so one concern is the potential to change the chemistry in sewers and in water treatment plants.
Tony - Sewers is really easy because it's dark in a sewer and the catalyst only works when it sees light. So if a piece of titanium dioxide sees light then it's a photocatalyst. If a piece of titanium dioxide is in the dark, it's a lump of rock. Likewise in the sewage front, 2 millimetres of water is enough to filter out a big proportion of the UV and then the question is, what do titanium nanoparticles do to the bugs in the sewage plant? And that's absolutely something we're looking at.
Ben - The researchers are now working closely with a manufacturer of environmentally friendly cleaning products to commercialise CatClo and they hope to have something in the market within a couple of years. They hope that as well as the wider environmental clean-up, these additives will benefit people suffering from asthma and respiratory problems. And Professor Ryan also highlights one other less obvious benefit.
Tony - And for Yorkshire man like me, the best thing is it's a license to fart.
26:25 - Foetal DNA in Mum's Brain
Foetal DNA in Mum's Brain
Male DNA, almost certainly left over from a male foetus, has been found lurking in women's brains, according to research published in PLoS ONE this week. It's unclear what effect this may have on maternal health.
Foetal Microchimerism is the process by which foetal cells and DNA can escape the womb and get into the tissues and blood stream of a pregnant woman, but this work, carried out by William Chan of Fred Hutchinson Cancer Research Center and his colleagues, is the first to show that these cells can reach and persist in her brain.
The team looked at brain samples taken from the autopsies of 59 women and tested for the presence of Y chromosome DNA, which can only have come from a male. 63% of their samples were positive for male DNA, showing not just that it's very common, but also that it's very long lasting - the oldest female positive for male DNA was 94 years old.
Generally, the blood brain barrier should keep foreign cells like these out, but changes during pregnancy can cause the barrier to become more porous, giving chimeric cells a window of opportunity.
This is a small study, so any potential effect on maternal health is unclear. Foetal microchimerism has previously been shown to be a double edged sword. These cells may aid tissue repair and protect against breast cancer, but may also increase the risk of autoimmune diseases and other cancers.
Women who have had more children also seem to be at greater risk of developing Alzheimer's disease, so the researchers were very surprised to see that women with Alzheimer's had a lower prevalence of male cells in the brain and in particular in brain regions most affected by the disease. This finding raises more questions than it answers, but does suggest that microchimerism may have some protective effect on the brain.
28:43 - The bright-side bias
The bright-side bias
The brain basis of the human tendency to always look on the bright side has been revealed by new research.Scientists have known for some time that volunteers will take on board new information that has a positive message much more readily than negative information, which they tend to ignore. Some speculate that this "good news / bad news effect", as it's known, might underlie financial bubbles, and psychologists also suspect that it accounts for natural optimism, over-confidence and poor judgements made during critical medical or health situations.The reason for this has been a mystery. But now, UCL scientist Ray Dolan and his colleagues have used a technique called TMS -that's transcranial magnetic stimulation - to temporarily deactivate a brain region called the inferior frontal gyrus (IFG), making the effect disappear.The inferior frontal gyrus has previously been linked to self-inhibition and also to updating what we believe about ourselves and the world around us. Publishing in PNAS this week, the UCL team asked a group of volunteers to estimate the likelihoods of their suffering 40 different adverse events ranging from developing Alzheimer's to being robbed. The subjects were then presented with data showing the true frequency of each event in their representative populations. While they were reviewing this data, TMS was applied to the subjects' brains to switch off either their right or left inferior frontal gyrus, or an unrelated "control" part of the brain. They were then asked to re-estimate their risks for each of the adverse life events they had considered previously.The researchers found that inhibiting the right IFG, or a control brain region, had no effect. Just as before, the subjects revised their estimations in response to good news - when they found out they were less likely to suffer one of these events than they had thought - but they buried the bad news. Inhibiting the left IFG, though, produced a radical rethink on the part of the subjects, with 60% of them ceasing to ignore the bad news as they had done before.( Examining the data confirmed that the effect wasn't because subjects were less good than they had been previously at incorporating good news, rather their ability to take on board the bad had improved. )As the researchers point out in their paper, there are positive benefits to regarding the metaphorical glass as half full rather than half empty, because emphasising the pros and ignoring the cons "increases exploratory behaviour and reduces stress and anxiety, a factor that has links with physical and mental well-being..."In other words, it has probably evolved to help us to avoid depression and anxiety, and so be better able to function in the world...
32:10 - Bacteria-repelling catheters, and element 113
Bacteria-repelling catheters, and element 113
with Chris Loose, Semprus Biosciences, Phillip Broadwith, Royal Society of Chemistry, John Rogers, University of Illinois, Ken Lukowiak, University of Calgary
Bacteria and other debris can become stuck to catheters inserted into the body, potentially causing infection and blood clots, also known as thrombis, to develop. Now a group of researchers across several American Universities and Semprus Biosciences, have developed a technology that could solve this problem. The team developed a catheter that creates a water barrier on its surface, which prevents blood platelets and bacteria sticking to the device. Co-author Chris Loose explained the importance of the technology.
Chris - This work is important because there's a whole host of medical devices that have complications in body, whether they're related to bacteria or related to blood clotting. So we see this as a really broad problem and this is really a first step we're showing technology has a nice long lasting performance benefits for reducing both this bacteria as well as thrombis over multiple months of blood product exposure, so a dual functionality and a long term. In laboratory trials, the new device had 99% less unwanted material attached to it than conventional catheters, even when left in place for 60 days. The work was published in Science Translational Medicine.
Element 113 found
The previously highly elusive element 113 has been discovered by Japanese scientists at the Riken laboratory, after 9 years of work.
The highly unstable and short-lived element was made by firing millions of atoms of a lighter element at a heavier one and observing the decay chains of the atoms created from the collision.
However, it's not certain that the Japanese team, publishing in the Journal of the Physical Society of Japan, will be able to claim the discovery, as other groups in Russia and the US have also made claims to element 113, and any new discovery must be ratified by a working group of the International Union of Pure and Applied Chemistry, Iupac, as Dr. Phillip Broadwith from the Royal Society of Chemistry, explained:
Phillip - There are other groups which may also have claims towards element 113, so it depends whose evidence the working group decides is the most convincing and which came first, as to who gets to name the element.
A group of engineers have created implantable electrical devices that harmlessly dissolve after a pre-determined time period removing the need for further surgery to remove them.
The devices use materials that are already used in the body, such as magnesium, which is currently used in the form of stents to keep arteries open, and a form of silk, currently used for stitches. The thickness of a layer of magnesium oxide covering the implants controls how long they function for, as this substance dissolves at a known rate within the body.
Prof. John Rogers of the University of Illinois, an author of the paper in Science and a member of the multi-university team, explained the challenges the devices needed to solve:
Improving snail memory...with chocolate
And finally...the memories of pond snails have been improved by giving them a chemical found in chocolate, green tea and blueberries.
Researchers at the University of Calgary, Canada, trained the water-dwelling snails to essentially, hold their breath while immersed in water, with or without the chemical epicatechin dissolved in it. They then tested the snails' ability to remember the training, at regular intervals, and found that those immersed in the chemical-containing water could remember the training, for days, instead of hours afterward.
Co-author Professor Ken Lukowiak explained what was happening:
That work was published in the Journal of Experimental Biology.
36:40 - SPACECAST - Forecasting Space Weather - Planet Earth Online
SPACECAST - Forecasting Space Weather - Planet Earth Online
with Richard Horne, Sarah Glauert and Nigel Meredith; British Antarctic Survey
The Antarctic is associated with explorers, penguins and glaciers but the South Pole is also the perfect place for space research. The British Antarctic Survey is part of a collaboration that produces Spacecast - a space weather forecast that helps protect satellites by predicting particle radiation from the Sun.
Planet Earth podcast presenter Sue Nelson went to meet three members of the Spacecast team: Sarah Glauert, Nigel Meredith and - the first voice you hear - project coordinator, Richard Horne...
Richard - We're making a forecast right now, We're taking information from various satellites and from ground base stations, we're putting that into a computer model and we're forecasting up to three hours ahead what the radiation levels are in space for satellite operators.
Sue - Nigel - you're involved in some of the input that actually goes into making a forecast. What sort of things does this computer simulation need from you?
Nigel - That's right. I'm producing models of the waves in space which have an influence on the radiation belt environment. I've put together a database of waves from five different satellites incorporating data from approximately 16 years worth of observations to produce a global model of the waves in space.
Sue - When you say waves, which waves in particular to you mean? Microwaves, radio waves?
Nigel - These are low-frequency waves at the lower end of the radio spectrum with frequencies typically between about 20 hertz and 20 kilohertz so they are in the audio frequency range.
Sue - Audio - so does that mean we can hear them?
Nigel - It means we can play them back and listen to them as if they were the natural waves as they actually occur and I believe we have an example on the computer that we can listen to now...
...Well, that wave that you've just heard there was whistler mode chorus which is a particularly important wave which can accelerate particles in the radiation belts up to very high energies and that is one of the emissions that we observe.
Sue - So in a way it's like particles of surfing on these waves. The faster the waves then they quicker they get here.
Nigel - That's right. The particles themselves can actually surf on the waves and gain energy gradually in small increments but by surfing on many waves over time and they can build up their energies to very high energies up to the so called MeV energies which are representative of the "killer electrons" and they can be accelerated to these kinds of energies on the time scale of typically one or two days.
Sue - Now, Sarah, you're putting this information into the simulation. There must be quite a few variables?
Sarah - We certainly need, for instance, the activity of the Sun, the levels of geomagnetic activity going on out in space. They all go into the model. There are various other ways that interact in different ways and drive the particles closer to the earth generally, that sort of thing. There are all different aspects that go into the model.
Sue - How accurate is it? How do you test its accuracy?
Sarah - Okay, we developed the model by running it as a simulation not as a forecast so there are periods of time for which we have satellite data that we can actually try and recreate using the model, so that gives us some idea of how well we're doing. And if you look on the SPACECAST pages you will actually see data from the GOES satellite and a model prediction of that data. So you can actually tell for yourself how well we're doing and you will see there are times which we do well and there are times at which we don't do so well.
Sue - And what are the timescales involved here? What is the timescale between effectively the Sun belching and us feeling its breath?
Nigel - That can vary. The fastest material can flow off of the Sun and reach the Earth is something like 17 hours. But typically, usually, its around two days, two to three days, something like that. Once that hits the Earth's magnetic field and disrupts the Earth's magnetic field that's when all these waves come into play accelerating the charged particles and that's a process that occurs inside the Earth's magnetic field and that then may take typically a day, maybe two days, something like that.
Sue - Richard, you're a co investigator on a NASA mission that launched only a few weeks ago to study the Sun's influence on the Earth. How will this mission complement what we already know?
Richard - The radiation belt storm probe is a very important mission. It is going to measure very low frequency radio waves, and that is going to help us improve the forecasting system. We are going to access that data, process it and then include that into our models and help verify our models and actually improve our forecasting capability. It is going into a region where we don't really have very much data so that's very important for us and here at the British Antarctic Survey we have a co investigator status on the mission and I think we're the only UK group to have that and that's very important for us and it's a very important international collaboration.
42:06 - Protecting Neurons from Age-Related Decline
Protecting Neurons from Age-Related Decline
with Dr Michael Coleman, The Babraham Institute
Ben - Over time, nerve cells or neurons can become damaged and they can sadly die or they can lose their connections to their neighbours. We've already heard how when this happens in the brain it leads to a cognitive decline with age. Now, Dr. Michael Coleman is a Neuroscientist at the Babraham Institute and
he actually joined us back in February 2010 - I can't believe it's been 2 ½ years! - to talk about the discovery of a factor that keeps nerve cells alive when they're damaged by a stroke or by injury. So thank you ever so much for joining us again. Before we go on to look at the latest developments on your work, today, we're talking about ageing. What does this nerve degeneration process have to do with ageing?
Michael - So, in answer to one of your earlier questions, loss of nerves and the white matter tracts in our brains is certainly something that is taking place in your age group and even in people in their 20s. We don't really notice the effects of that until at least middle age because we are born with more than enough connections in our brains to compensate for that. But it is an on-going process. It happens throughout adult life and certainly, when you get into older age, then this can start to have a very significant effect on cognitive performance, and predispose to age-related disease. So, these are two very important reasons to understand this process.
Ben - Do we know why we actually lose these? Are they only the result of injury or accident, or do we naturally lose some in the same way that earlier, we were hearing about senescent cells, which are cells that switch off and stop dividing after a certain time? Do we see the same thing in nerve cells?
Michael - We're certainly naturally losing them all the time and the exact reason for that, we don't know. That really is part of what my group now aims to find out. So, we've worked for a very long time on mechanisms that affect the survival of our nerves after injury and in certain types of neurodegenerative disease. And ageing if you like, is a big new growth area in biomedical science. If you like, we're catching up with the pensions industry and the health service in realising that this is a very important issue to deal with. And so, many scientists now are asking, what can they do in the areas that they have already specialised in that can be related ageing and how can they bring some understanding of the mechanisms in that area.
Ben - Now, when you joined us 2 ½ years ago, it was to talk about a protein that appeared to preserve these nerve cells. Could you just take us to how that works again?
Michael - Yes, many proteins need to be carried along our nerves to keep the more extreme ends of those nerves alive and functioning. And among those many proteins, we identified one that was a limiting factor for the survival of the distal nerves or axons. We were able to do that because there is a particular spontaneous genetic mutation in mice - a harmless mutation that enables those nerve cells to survive for longer and we understood how that was working. Essentially, it was compensating for the loss of a normal protein in those nerves when they are injured.
Ben - So, the idea is that if you had a stroke for example, you would be able to administer some of this protein and that would help to keep those nerves ticking over until you could then restore normal function through surgical intervention or whatever it may be.
Michael - Yes, so either to administer the protein or to administer a drug for example which wold boost the activity or block the activity of a related protein and thereby, alter the outcome of the whole pathway.
Ben - So, does it suggest that actually, tweaking these genes or taking this drug could also prevent the age-related decline and not just the stroke or injury-related decline?
Michael - Well, that's really what we now aim to find out. One important point about research into ageing, it is inevitably a very slow process because ageing itself is very slow. We might think in terms of an individual research project which is typically funded for 3 years. If you're working in mice which live for 2 years for example, that's a significant part of that research project. So it does take inevitably a certain amount of time to do, and actually, one direction that we are heading now is to ask, what happens to this protein during normal ageing and is that one of the key determinants of this age-related axon loss?
Ben - Again, when you joined us last time, this was all being done in the dish. It was cell culture, you were looking at. You just mentioned mice. Are we seeing a genuine activity of this protein in mice as well as in cell culture?
Michael - Yes, so this is unpublished work. It's very important that the work goes through a peer review by other scientists before we announce the full results, but the early indications are looking to us quite clear that what we saw in the dish, in culture situations is indeed the case in mice, yes.
Ben - Now, cells do have a natural way of dying off. This is apoptosis or programmed cell death. It's very important for avoiding tumours and so on. Are we increasing risks by keeping cells alive that wanted to degenerate, to no longer be alive?
Michael - Well, this is a very interesting question. I think when I do a seminar to other scientists, I think one of the most frequently asked questions at the end is, how did we evolve a process through which we can rapidly lose our nerves after an injury? What could possibly be the advantage of that? And yes, that's certainly something we aim to get to the bottom of. One of the possible reasons for that is that if there is on-going loss of axons within our nerves during ageing, and within our brains, that has to happen in a very controlled way. If it gets out of control, there is a serious risk of it damaging the neighbouring axons within the nerves. It can be many thousands of axons within a nerve. If one dies, you want to limit the damage to that one axon and not to take out its neighbours as well.
Ben - Now, we've been talking about cognitive decline today, so I think we may be thinking mainly about nerves in the brain which is of course just a mess of nerves and nerve connections. But presumably, this will all apply for the nerves that have incredibly long axons as well as the nerves that run down the spine, and run down into our extremities. It's not solely associated with the brain.
Michael - Yes. For a science which essentially only has to be observational, our understanding of age-related axon loss is really quite basic at the moment, the international scientific understanding. That's an area that, as a very first step, we need to get a lot more information about which areas of the brain and the rest of the nervous system are losing axons and neurons more rapidly. And when that happens, many axons in the brain are very highly branched when you come to their extreme terminals. There are some that can have upwards of 100,000 branches at the end. Now, there are some very preliminary, very early stages of information that much about loss occurs in reduction of the number of branches rather than a loss of the main axon trunk itself. But that's only been shown in some very specific areas of the brain and we need to understand much more about whether that's a general phenomenon throughout the brain or whether it's only in some areas.
Ben - And just finally, only fairly recently have we seen good solid evidence for neurogenesis, the idea that throughout our lives, we're still forming new nerve cells. Is this protein related? Are you likely to be able to encourage more new nerve growth or is this purely protecting the existing ones?
Michael - Yes, the understanding of neurogenesis has been one of the big stories over the last 10 years or so in neuroscience. What we don't know yet is whether those newly born neurons contribute to long projections around the brain or whether they influence only the very local environment in certain areas of the brain. So, whether this protein is actually involved in any growth of axons by those neurons, it's really still unknown at the moment.
How does reduced calorie intake increase life span?
Michael - There's been some very compelling evidence in invertebrates, in flies and in nematode worms that reduced calorie intake is somehow boosting the cell's ability to withstand all kinds of stress. So, the shortage of nutrients for those cells is a stress in itself. By switching on the resistance to that, it also switches on resistance to many other kinds of stress as well. So that's the best that we understand at the moment that it seems to be some kind of general upregulation of ability to withstand stress.
Ben - And I think it's probably important to point out that when we're talking about calorie restriction, we're not talking about not having that extra doughnut or having a slightly smaller bowl of cereal in the morning. These calorie restriction experiments are really quite extreme, aren't they?
Michael - Yes, they are quite severe. I do know that there are some human studies going on to test this, but I certainly wouldn't like to be a subject in those experiments.
How can people with hip problems do cardiovascular exercise?
Lorraine - There are exercises that you can do using your arms and the rest of your body that will generate aerobic activity. So, I don't think it's the case that people who can't move very easily can't do any exercise. It's more difficult if you can't, but I certainly think that you can lift weights and do exercises with the upper part of your body that would help to increase your cardiovascular health.
Ben - I think there must be a range of physiotherapy things you could do. I certainly see people using hand bikes where you pedal along, but instead of using your feet, you're using your hands.
Lorraine - Yes.
Are some cells immortal?
Michael - Yes, there certainly are cell lines that we can grow in the laboratory. They originate from normal types of cells. They may have become tumorous or cancerous in the body in some cases, or transformed as we call it within the laboratory. After that, they can grow for very long periods of time, yes.
Ben - So, these are immortal cells and they're essential for research.
Michael - They are essential, but they do have limitations. They have a lot of changes within the DNA. They can sometimes have the wrong number of chromosomes, so they can tell us some things, but we often have to then confirm that in more normal cells.
53:37 - Would self bone marrow transplants reverse aging?
Would self bone marrow transplants reverse aging?
We put this to I'm Professor Tom Kirkwood at Newcastle University...
Tom - Ageing is complicated. We know that the underlying reason that the body ages is that as we live our lives, our cells accumulate a whole host of small faults, damage affects the DNA, proteins, membranes that make up the cells. So basically, the ageing process is driven by things going wrong, cells become damaged, and that also affects the stem cells of the body. It used to be thought that stem cells could keep going more or less indefinitely, but actually, we know that stem cells that underpin many parts of the body do themselves experience some form of intrinsic ageing.
So, in theory, one might think that a good way to combat some of the effects of ageing would be to replace the cells within the body that had been damaged by this accumulation of faults with cells that are somehow less damaged. And the idea that you could use your own banked cells from earlier in your life is an interesting one. There are problems with that though, ageing affect all the cells and tissues of the body, so simply rejuvenating one particular population of cells maybe do it for that group of cells, but it's not going to do anything about all of the rest. So, it's not going to be a universal effect.
Hannah - Self-bone marrow transplant may not reverse the whole body ageing effect, but it could be used to reverse a specific aspect of it. Bone marrow stem cells replicate throughout your life to produce your blood cells including white blood cells such lymphocytes which act as soldiers, fighting off infection in your body. Your immune system is one function of your body profoundly affected by ageing which is why older people are more likely to succumb to infections. So, could injecting yourself with your younger fresher bone marrow stem cells keep the flu at bay in later years?
Anne - My name is Anne Corcoran. I'm a Research Group Leader at the Babraham Institute in Cambridge and I work on how the body fights infection. Older lymphocytes grow more slowly and make far fewer new antibodies, the proteins that recognise and get rid of infections. So, a younger version of your bone marrow that still has younger stem cells to generate younger lymphocytes might help your immune system to fight infection.
Hannah - In which case, should all under 40s be rushing to have their bones drilled in order to harvest their bone marrow stem cells and bank them to help boost their immune systems later in life?
Anne - Taking a bone marrow sample is not a trivial procedure. It's not like taking a blood sample. Also, we don't yet know exactly to what effects of long term storage of bone marrow are on its efficiency.
Hannah - Instead, Anne suggests, boosting the older immune system by reducing stress, getting enough sleep, having a healthy diet high in antioxidants, exercise, and some good old physical contact like hugs and handshakes to release endorphins and boost the production of antibodies.