 So thank you very much for inviting me to do this webinar today. This is a new experience for me to do one as a webinar. So do let me know if there's any. I'm having to make sure that I can see all the notes to say, oh, everybody's saying yes, yes, okay, that's fine. And I recognize some of the names. So those of you I know, welcome, and I'm just nice that you came. So today I'm going to tell you about the longest national birth cohort study in the world. It's a study that I've worked on since 1987. And I want to tell you about how it's contributing to our understanding of the role of social and biological factors across life on health and aging in later life. And I'm just going to make sure I can get my slides. There we go. So let me just introduce the study briefly. It was based on a maternity survey of all the births in a week in March 1946. There were 17,000 of them. And of course, this was pre-computer days. And what happened is that a representative sample of almost 5,500 babies were followed up, have been followed up ever since. And they're about to celebrate their 70th birthday in March. We're having two big parties for them, which they thoroughly enjoy. And they've been followed up 25 times. And they have been an amazing group in terms of having a sort of 80% response rate on almost every occasion we've been out to see them. Now, the secrets of its longevity lie, I think, in the fact that it's always addressed issues of science and policy and has been of interest to first the parents of the study members and then study members themselves. And it has always brought together social factors and biomedical factors to see how they affect in initially. It was how they affected pregnancy and childbirth. And one of the things in the 40s that it showed was the really strong social inequalities, both in the care of the mother before birth and in the outbirth outcomes. And that was one of the reasons that funding was able to be maintained to follow up these study members. And, of course, this was just at the beginning of the National Health Service in our country. And that original pregnancy and childbirth pregnancy study really influenced how services for mothers and young babies were set up. And so in its early years, of course, it was a study of development. And they were followed up almost every couple of years at that time, both the mothers and school doctors and teachers and eventually the children themselves were asked many questions. And we have special data in terms of serial measures of height and weight, several tests measures, very detailed measures of their cognitive functioning at several times in childhood, what they ate for, you know, feeding when they were age four, and a whole wealth of data about their environmental experiences. So as these children grew up, one of the things they were able to do was to start to look at the childhood origins of health first when they were young adults. And in fact, this study was one of the first to look at the, actually, look at the childhood origins of respiratory disease in the 1970s. I'll come to that in a minute. And also it was the first, many of you all have known the Barker hypothesis, but actually David Barker, who worked with us on a number of papers, our study was the first to show that low birth rate was related to higher blood pressure in adult life. And then we've also have a very strong social component, particularly in childhood, when we looked at educational progress and then over the years, looking at their life chances beyond health in other areas of their life, their jobs, for example. But as they've got older, it's focused very much on adult health and aging. We had three very important follow-ups at 36, 43 and 53, and we really specialized in cardiovascular cognitive and musculoskeletal functions. This study has been funded by the Medical Research Council since 1962, and that has also really added to its ability to do innovative science and to continue over the years. I took over as the director in when they turned 60 and with a plan to actually get the adults back into, normally nurses had gone to people's homes in adult life and health visitors in childhood. So we mostly went to people's homes and did as many kinds of tests as we could in their homes, but in their 60s we got them in for a clinic data collection so that we could do some more detailed, for example, imaging of their hearts, cardiac and vascular imaging, bone and body composition scans. We got them to wear activity monitors that measured physical activity and heart rate and to collect more biological samples. And now at the moment we're just finishing the home visit at 69 years, and we have also started a neuroscience clinical sub-study. So we hope that around 500 of these study members will come into Queen Square in London to actually have very detailed brain imaging and PET scans and many other tests, and so far we're at the beginning of that and 100 have so far come in. And just the pictures on the right, one of the ways we've kept study links with them is through birthday cards because they're all born at the same time. So they're the only ones who've never forgotten their birthday since we started doing this at age 16 and they love these cards, and the one at the top is the one we did for the 65th, which shows a whole range of different cards we did. And then at that time, Nature also did a major article on the study when they were 65 and there was called Lessons of a Lifetime, and I will actually return to something about that later on. So that's the study. I want to give you a little bit of historical perspective here. So very brief, as you can see, first slide over 70 years of the 20th century. So I would say, broadly speaking, that in the first part of the 20th century really was conventional wisdom in public health and that early life could affect adult health. There was less very little empirical evidence, but there was some that I'll show one aspect on the right, which is early cohort analysis done in fact in 1927 where they plotted the death rate by age, by year of birth rather than by year of death. And you can see the parallel lines there, which means that each successive generation was actually living longer at each age than the previous generation. And they interpreted, some people interpreted that. Many people interpreted that as the importance of childhood conditions on adult health. There was also biological and behavioral research into critical periods, both of animal and human development. And I give a little quote at the bottom on the right-hand side. Stockard from the States in 1927, he was doing animal studies and talking about the critical moments in the origin and development of organs when they suffer, particularly likely they might suffer from an unfavorable change in conditions. So if you, those of you again who know the bark hypothesis will realize that some of these almost, some of Barker's ideas really echo some of these quotes. But in the post-war period, public health and epidemiological interest in early life factors waned and that was because there was this, if you like, epidemic of cancer and heart disease and adult cohort studies were set up that focused on chronic diseases and on adult lifestyle and in fact were very successful in identifying risk factors that could help prevent the development of those diseases. But at the same time there were more birth cohort studies set up than child development studies, but they had a very, very separate history. Outside epidemiology, the life course perspective did continue in other disciplines, for example in psychology and anthropology. And in fact, epidemiology, the revival in this life course perspective has, the epidemiologists have been rather late in coming to it. So I won't spend much time here, but just to let you know that there's one of the, what we call the 1946, the NSHD, the cohort that I lead. There are also later British birth cohorts, and I'll show you a few more of those later on. So during this time there was, I put reasons on the screen why in fact these studies were actually continued to be funded. They were actually very low, they were very good value for money, they weren't actually that expensive. And you might be interested that Helen Pearson here who wrote the article in Nature on the 65th birthday, she's a scientific journalist who working on Nature features editor. She has spent the last five years writing this book which is about to come out in Penguin in 26 March 2016 about the whole social history of these studies and about the scientists who ran them because many of the scientists have worked on these studies, have worked on them, have made them their life's work. And then I've also pointed out there were quite a lot of regional studies going on in that time of child health and development and there was a real strong tradition in social medicine and the development, whole development of pediatrics, child psychology and psychiatry really fed into these cohort studies. Again, I mentioned in the last point how there were also studies set up in other countries, sort of many of them set up on the kind of model that the 1946 cohort had been set up on. Oops, I'm pressing the wrong button, I beg your pardon. So from the 1970s there was growing evidence of this link between childhood and adult health and what I have said that it was scattered and it did sow the seeds for this revival in life course epidemiology. I've mentioned about how our study showed the childhood origins of respiratory disease and on the right you can just see some illustration adapted from a publication in the British Medical Journal in 1973 just showing how the importance of respiratory disease at age 20 of early infant chest illness, air pollution, early childhood social class as well as current smoking. But there were also studies, the Hagaston morbidity studies that took place in Maryland in the 1930s. There was a follow-up of the children in that community study and there's some interesting data showing again before really this idea really took off that children who were of underweight but then who became overweight in adult life were more likely to have what they called hypertensive disease. We've got the Dutch hunger winter that Mervins, Schuster and Sienestein, the four and some of the first studies that they led in the 70s. We've got the Bogle loser study starting to track through childhood the conventional adult risk factors. We've got the ecological studies done by Forstel to look at how childhood poverty in the 1920s and 30s linked to cardiovascular mortality 15 years later. All these were scattered bits of evidence. What really was the catalyst for bringing back this idea into mainstream epidemiology was David Barker's work on the fetal origins of adult disease. I can't see your faces so I'm assuming that most of you know something about this. It was originally called the fetal origins of adult disease. It's become known eventually as the developmental origins of adult health and disease. It was very much focused on factors initially in uterine factors that might have long-term effects. It saw its long-term effects on particularly cardiometabolic disease and respiratory disease. That was very much the important catalyst. In order to follow up some of these ideas about childhood being important for later life, the UK is particularly lucky to have these birth cohort studies and these historical cohort studies. You can see the NSHD in the middle with its longest follow-up. As well as the three national birth cohorts, I've mentioned ALSPAC, the Millennium Cohort and Southampton Women's Study, and shown again how far they have got along the lives of monitoring and looking at for longitudinal associations between early back and later health and some of these, like ALSPAC, are being extremely productive. Then at the top, the historical cohort studies where you can see the Hartfordshire Aging Study, for example, and the Hartfordshire Cohort Study. These were cohorts that were set up by David Barker's group where they had data sometimes in infancy and about birth weight and infant health, but then no further data until they revitalized these cohorts later on in life. Then there's a whole range of Scottish cohorts that collected data on childhood more, to do with childhood cognitive function mainly and social circumstances, and again were revitalized when this growing interest in the early life origins of adult health came. They were revitalized to be able to test some of the hypotheses. So I would say there are sort of three main stages of the current revival and life course epidemiology. Aging is the last stage, and I'm going to talk more about that in a minute. But I just want to remind you that the actual term life course epidemiology was actually coined in 1997 with this book that I co-edited with Joa Ben-Schlomo and that many of the people who names you would know if you know this literature, we reviewed the evidence for pre-adult risk factors, primarily on cardiometabolic and respiratory disease because that was where the focus was at the time. I'm not going to go through the things that we showed, but suffice to say that this review supported many aspects of the kind of bulk hypothesis at the time. But one of the things that we tried to draw out here was that we needed to develop three different models of disease causation further. So the fetal origins, I've already sort of mentioned, it started very much to focus on the fetus, but we were showing and others were showing the importance of critical or sensitive periods in the postnatal period during childhood and, in fact, as I'll show later on during puberty and later on in life. So that needed extending. The adult lifestyle model was being extended and needed to be extended more to look at the origins of these important behaviors that affect health so much in adult life. And then the social causation model, which with the focus on socioeconomic factors, again, that was very much adult-based socioeconomic factors at the time. And as the birth cohort studies matured and other studies, they were able to show how important the childhood socioeconomic circumstances and other childhood environmental factors were for adult health. So that's where we sort of came in and then the next stage, I would say, was from about the turn of the century when people really started to develop life-course epidemiology as a research field. It was applied to many more health outcomes and I list some of those here. We started to develop a conceptual framework much more. We started to develop our life-course models and methods for analyzing the data and for testing the models. There was a lot of evidence synthesis going on in terms of systematic reviews and meta-analysis, particularly of the sort of epidemiological studies that Barker had generated, for example, very wonderful systematic review on diabetes, the birth weight and diabetes that Peter Winkup did. And increasingly, we were focusing not on necessarily disease endpoints, but looking at change both in the exposures and in the health aspects of health that we were interested in in later life. And we were in particular looking at measures of function. I mean, obviously, things like blood pressure and measure of function, but there's a whole aspects of our functional health where, in fact, we knew not very much about how it changed over the life-course. And these measures of function give you a way of studying health across the life-course. Growth trajectories also became very important in growth trajectories at that time. I'm going to have to move on because I realize without any feedback from audiences, it's hard to know how long things are taking. So we will move on. So the third phase was when, as these birth cohorts really matured into adult life, they met up with the aging cohorts that had started sometimes as early as 50, but generally over 65. And we started seeing how many things we had in common. And one of the things we had in common was this real interest in functional trajectories. And I show this sort of very simple but very, I think, useful diagram here showing how many levels, many aspects of function increase during growth and development hit some kind of peak or plateau functional structural reserve, you can see. And then there's a slow rate of decline in adult life. And of course, what we're interested in is how early life respectors can both affect the peak and potentially the decline and how, whereas adult life respectors are mainly going to affect how people change post-maturity. So this really brought us into studying aging, which of course is, you can define as the progressive generalized impairment of function, I would say post- and probably post-maturity, although obviously in some aspects you can argue, aging starts from conception onwards. And this was the start of our Halcyon project, which where the book that came out in 2014 was putting together of all the work from a consortium of nine cohort studies looking across at different aspects of healthy aging and some of the factors across life and looking across cohort comparisons. So our approach to studying healthy aging, defining healthy aging, of course, it's a concept. It's a nightmare in terms of there's been a lot of, I think, endless debate rather sterile debate in many cases about how to define healthy aging. I haven't got time to get into that, but I would say that for our approach, we've tried to separate what we would call healthy biological aging, which we would say is that both the chance of survival to all old age, not everybody survives, even to have an older age. We have to look at that. It's about delaying the onset of chronic diseases and particularly it's about this optimal functioning for the maximal period of time, both in what I would call physical and cognitive capability, which I think of as kind of multi-system measures at the individual level and also functioning at the body system and cellular level. And of course now there's this huge interest in biological aging, the sort of molecular measures of biological aging. And for here, age is a main risk factor. And whereas the other aspect of healthy aging, which is, I think, to do with psychological and emotional well-being about positive emotional health, participation, engagement, those kinds of things, generally shows a more U-shaped relationship with age. It generally also has a weaker relationship with chronic disease and function. And I'm not really going to talk about this second aspect of healthy aging. I'm going to focus on the healthy biological aging. And you can see, this is from the 1946 cohort, a measure of well-being by the number of clinical disorders. And you can see that although if you've got no clinical disorders at age, this is at age 60 to 64, you have higher well-being. And if you have lots of them, you have lower well-being. Where most people are in the middle, there actually really isn't very much variation in the mean. So let me get on to some many more, so quite a lot of examples that I want to show you. So I thought I'd start with just survival, just so in our cohort already by 65, at least 15% of them had already died. And you can see the causes, the main causes of death here. And we've already published many papers about premature mortality. And I list the kind of aspects that you can see, the number of aspects in childhood to do with childhood social circumstances, childhood cognitive ability, stunting in childhood, but also other things from adolescence onwards, psychiatric disorder. And I'm going to talk to you much more about adult physical and cognitive functions. And I just give you illustrate here, this is survival by childhood social class. These are the women who were born into the non-manual classes in early life. And you can see they're much better survival than the red is the manual women who were born into a manual class who are much more like the non-manual men. So a great big two-fold difference for the women. The difference is for the men in this particular case weren't just striking, but you can see they're beginning to really, the orange bar, they really begin to pull away. These are the manual males who have the worst survival rates. And these are, if I show you anything by childhood social class, I think you just have to take my word for it today that we have always looked at whether these effects are independent of adult social class. So I'm looking at factors that seem to have long-term effects which aren't purely linked through the very strong link between social mobility, social economic circumstances, being born poor and staying poor, for example. I keep pressing the wrong button for moving on. In terms of the onset of clinical chronic diseases, in our study, when we got the study members into the clinic in their early 60s, we actually looked at what we call clinical disorders. So these were, you can see the definitions, what we had the 15 clinical disorders we were able to get very good measures about. These were aspects of health that require at least monitoring and not usually treatment. And we wanted to see how extensive these disorders were as people were approaching retirement age. And as you can see here on the golden bit, only 15% of the cohort had none of these disorders. In fact, it was typical to have two disorders on average. And many of these disorders, I'm going to show you a few examples, have their origins in earlier life and are socially patterned, particularly the cardiometabolic disorders, but also several of the others. And indeed, even if you're not thinking of childhood, we had done a very full assessment. When I first arrived in the 80s, we'd done a very full assessment of their health status at 36. And we were able to show 30 years later how strongly it was related to their health as they hit retirement. So, and then in terms of the physical and cognitive measures that we've used in this study, I've shown you some of the areas that you, these performance tests we have tried to capture. And I've also shown you they're not exactly the same measures in this performance score, but they're showing you here the number of clinical disorders, the mean difference in the performance score. This covers cognitive and physical performance scores, a mean difference we found at 60, at age 64. And you can see the strong gradients in the means, so between function and these clinical disorders. So, which I, if you compare to when I was showing you with well-being, which was actually nothing like as striking as that. So, I'm going to give you some examples now of, I'm going to start with the sort of early sensitive periods, prenatal infancy and early childhood. I'm not going to dwell on all of these as we go, just pick out a few examples. But I just wanted to point out how birth weight and pre-pure birth or growth has been shown to be related to cardiometabolic or respiratory bone health. It's these functional ageing measures I've just shown you, adiposity, cancer, menopause. We also have measures of motor and cognitive development, which seem to be very quite strongly related to functional ageing and its change in later life and to menopause. So, I'll show you all that. And then all these measures of childhood diversity that we have, again, related to a whole range of different kinds of outcomes in later life. And I've just put up three examples, and I'm very sorry, I realize some of the things haven't quite come out. This is showing the blood pressure, the effects on blood pressure of birth weight, so higher birth weight, lower blood pressure. And this is on the right hand a bit of that top figure. And the knob, this is showing how manual social class in childhood had higher birth weight. I thought it had higher blood pressure. And then just below that, there's breast cancer incidents and we were able to show, I want to show just a different example. It isn't always low birth weight. It's the problem here. We had heavier babies who were more likely to have premenopausal breast cancer in our study. And then on the left where it says different percentage difference in bone strength. Again, you can see these are conditional models. So anything above the line is saying it's good for bone strength. And these are weight changes between 0 to 2, 2 to 4, so on 4 to 7. So in the early period of life, weight gain in this cohort, which was not an obese cohort in childhood, was actually very positively associated with having better bone strength in when they were aged 60 to 64. Here's some examples of later sensitive periods. So let's look at puberty in adolescence. So one of the things in this cohort that really is striking is how much weight gain from puberty onwards was related, and I put to a whole range of those cardiometabolic, kidney, thyroid dysfunction, neostial arthritis, and again, dysfunctional aging. And here, we've looked at it in several ways. I'm just giving you two examples. If you look at the bottom picture where it says BAM at L, that's showing again, rather like the period, the figure I just showed you, here we have the weight gain from puberty onwards being highly related to fat mass, fat mass measured through DEXA in later life. We've also done things like overweight profiles. So here are some profiles of different weight trajectories on the right at the top by Silverwood, showing babies who were, people who were as children, they had high weight across life, some of them who gained weight, and those who maybe started as a chubby baby and got less. And these kind of profiles have been linked to many of these outcomes in that first line too, particularly this particular paper related it to chronic kidney dysfunction at 60 to 64. And then just for a different thing, I've shown the adolescent conduct disorder measures that we have again showing how knowing about, and these are not knowing about teacher ratings that will then produce these measures of adolescent conduct disorder, how those with the highest conduct disorder in adolescence have gone on to have the higher mortality rates. And then just we also need to think about middle life, and one of the things we've been finding that in midlife is the sensitive time for women there's a sensitive time for menopause. I think I don't have time to go into the detail of this now, but what you can see on the left are all the factors that predicted the timing of the menopause, of the early life factors, the adult factors, and now we're showing how menopause the tremendous force transition affects things, for example, like volumetric bone density, people's bone health in later life. And the two most intriguing early life factors are shown at the bottom, childhood cognitive ability predicting age of menopause and also parental divorce predicting age of menopause. I'm just trying to give you a flavor of the kind of things we've got. And in blood pressure, if we now just look at some of the cardiometabolic, so in blood pressure, no cohort has measures of blood pressure right across life. So one of the things we've been doing is putting cohorts together to look at the life course trajectory. And you can see here we have eight cohort studies, and you can see in the middle of life there is quite an acceleration in blood pressure after a sort of plateau in the sort of 20s. And one of the things we were able to show in this build on from this study that we did was to actually identify these two lines. We've got a group during midlife who had a high accelerated increase in blood pressure and a group that had a more sort of what is so-called statistically normal, at least increase in blood pressure. And these groups were differentiated by all these factors on the left-hand side, including childhood social class, the birth weight, some of the things we've talked about before. And what is interesting to me is that when we then got our measures of cardiac function and structure, we were able to show how change in midlife blood pressure was actually associated with left ventricular mass index and with different measures of diastolic dysfunction 10 years later. So building up across the life course, and just checking the time, how things move. Okay, so I want to spend the last few minutes. I've got really thinking about what I call physical capability, physical functioning. And here, again, we've done, this is just cross-cohort work, but taking 12 British studies of how strength varies across the life course to show how, you know, remember the illustrated diagram I had earlier, show how similar it is, and here's the peak in people's sort of 30s. So the Halcyon Systematic, it's a systematic review and showed, for example, how childhood socioeconomic position was very important for, well, was at least an important factor for physical capability because all the studies that had looked at this across the world, and here is the forest plot for walking speed. So the lower the socioeconomic position, the worse, and childhood, the worse for walking speed. So that gives more robust evidence that we're seeing this, not just in our cohort, but across the cohorts. And I show you a similar thing, a diagram that I showed you for menopause. Here are the early life factors that we have found, predict, related with physical capability at 53. So things like chair rises, standing on one leg with your eyes closed, grip strength. And now we're looking at how physical capability is impacting on other aging phenotypes in later life. And I give you two examples here. With chair rises, this weight gain in childhood was actually very positive. Those boys who gained weight in childhood actually did better chair rises, stand up and sit down chair rises 50 years later. And then from puberty onwards, the weight gain became a negative factor, as you can see in the turquoise. And then we also, to the right, showing how mean differences in standing balance by age at first walking and unadjusted, well, adjusted for sex, the white bar, and then adjusted for a whole range of things that I don't have time to go into, child and growth, adult weight change, social class, physical activity, health status. So there seem to be two roots into physical functioning in later life, at the sort of mobility level. From the early factors, the growth story, and in grip strength, for example, you probably know that people of low birth weight have lower grip strength in adult life. It's not just about the fact that we figure out to be smaller people and adults. So we have a growth story that varies, but there's a sort of general pattern across these measures. And then we have what I would call neurodevelopmental story. And as you hit adult life, then the in our cohort, the adiposity story becomes very important too. So I'm here just to show you, we talked about, remember the figure, you probably don't, there's a cool performance score, which I showed you at the beginning of the lecture. Well, here are the other components of it. And this is just showing, using relative inequalities. So comparing the top and bottom of the childhood social class scale, showing that each of these measures had about a 10% difference or more between the top and the bottom groups, meaning that, and because they very much are clustered together, meaning that for some individuals who have many of these factors, they could have a difference in their functional score of 66% compared to the healthiest group. So these just show you, and you can look at these afterwards, but I've just shown you a few examples. This is the whole range of the different factors that we've looked at across life that we're associated with. What we think is a very important aspect of adult aging in later life. And midlife cognitive function shares many of these respectors. I cannot possibly talk about those as well. And now we're into looking at functional change and also thinking about when these differences in these aging phenotypes really emerge. I'm very aware that it's quarter two and I've got a few more slides and I don't know whether to continue or bring it to a close. Can anybody speak to me as the moderator? Yes, Diana, I think it would be great if you could continue with the slides. Yes. Yes, okay, fine. So do stop me if you think that. I've probably got another five minutes or so, but in terms of the question about when the childhood socio-economic differences emerge or socio-economic position, we have measures of reported functional limitations from age 43. And you can see these are men and women and you can just see these differences between men and women of the manual and non-manual classes growing. A, that these functional limitations, the top is difficulty walking up and down stairs. The bottom is difficulty walking a quarter of a mile on the level. How much, how they're getting worse with age and how the differences are getting greater with age across the social classes and in fact by sex. In terms of trying to measure change, we are now only just getting our third measure of physical capabilities. So we can't do our multi-level models until March but we almost finished. So we did, but we did try and define some groups. People who were what we called between 53 and 60 to 64 or people who were low-low, always had low scores. People always had high scores. People who had meaningful, what we think is meaningful, decline and then this big intermediate kind of reference group. And what we're showing at the moment with papers under review is that as well as what you might expect healthier lifestyle, adult lifestyle is related to a higher chance of being in the high group and a lower chance of being in the low or the declining groups. So we are measures such as higher cognitive ability in childhood and similarly childhood manual being in the manual social class in childhood has a greater risk of being in the low or the declining groups. Some variation by test, but I think some very interesting it's much harder to show effects of early life factors on change in adult life. It's very quite easy to show effects on more associations with the level at any one, not at any one age. And of course we need to bring in and we've been bringing in the cognitive work dealing with dropout because of mortality, for example. Actually when you look at change and allowing for the dropout in mortality if you look at change across adult life in this physical and cognitive function you get a stronger decline and if you don't allow for that. So those sorts of things are really important. I've mentioned I just wanted to kind of as we draw to a close I just wanted to mention that which I haven't got time to go into some of the potential biological mediators on the pathways linking early social adversity and early child development or fetal development to aging. And it's interesting to me that from the many of you will know about Clyde Hertzman who unfortunately is no longer with us but the whole idea of the biological embedding of early adversity of early social adversity and Michael Rutter over here they picked up things to do with the genetic mechanisms. This is another talk but you might you should know about the IGA special issue on epigenetics in 2015 which brings a lot of this stuff together. Obviously many of us are looking at endocrine immune and metabolic systems to try and explain these pathways. Increasingly we can start both in childhood and adult life to really be able to image the brain and look at neural structure and function how these may be mediating pathways. And I suspect you can guess from some of the things I've said how this changing body composition as you get older you know you get your lean mass goes down you've got the fat infiltration of lean mass you've got your body composition changes you've also got how long you were when you first became overweight or obese and how long you've been exposed these things really can explain many of the links that I've shown you today. And below at the bottom of this slide it shows how different cohorts in the UK starting with the 46 in the grey right through to the 2000 Millennium Cohort Study in the red how the obesity and overweight trajectories are changing across the cohorts. You can see the first three there was an increase in adult life but somewhat similar but look at what's happening in the 1990s the Alsat Cohort and the Millennium Cohort really nervous stuff, you know scary stuff thinking about how that will impact on their later health. Right. And in our own cohort we show these very strong associations between not just obesity but the trajectories of obesity and overweight by childhood social class and we also show it when we look at something like fat mass index from the dexter. So this is I think a quite a powerful at least in our cohorts it's quite a powerful explanation for many of the outcomes that we see. So I won't dwell on these but just so you know we also look at things like inflammatory and decilial markers again childhood social class differences in addition to the factors in adult life and here these are things that definitely seem to be attenuated by adjustment for body mass index suggesting that's a mediator and the most recent one is a paper we published looking at different endocrine measures and looking at social class indicators across life and looking at composite hormone score to show how the lower the worst the circumstances across life the more adverse the hormone scores are. I'm not going to go into detail it's just a sort of over message so I'm coming to the end now last few slides. In terms of current priorities I would say that I've talked really this is a summary slide in terms of exposures and outcomes we're getting much now better characterization of the earlier and socially patterned exposures we're getting much better outcomes of aging outcomes we're getting better characterization of the mediators and the modifiers and we're looking at being able to understand much more about functional change across life and what drives that change and when important changes are observed and I think one of the most interesting things we're now getting into is very much identifying resilient and vulnerable groups people who seem to have either a very healthy aging despite having a lot of exposures across life or indeed the other way the group who are seem to be very vulnerable despite having actually quite either a good start to life or quite a good set of adult circumstances I've put two big challenges there perhaps for discussion but one about which I have about time to go into this talk one about identifying the type and timing of effective interventions which of course one of the main reasons we do that is to see whether we can identify people earlier on in life so that we can actually either modify or stop that bad trajectory in the first place and then on the right a really big important for science is that more and more we are involved with big data, mechanistic science precision medicine linking with bio banks and I think in terms of understanding particularly the social inequalities in health we need to be cautious but sensible in how these our cohort studies like in SHD integrate and work with the more big data mechanistic science that's coming through and is actually in many ways very interesting but with less deflectors from very important trends in social inequalities which I want to end with so I'm going to miss the last these two slides either just really to show stuff from something that's under review how how how the interest in life course perspective on health development and aging is really blossomed in the 21st century and I just want to end with these I don't want to end on bad note but I do think we should know about the trends in social and quality I'm sure you're all aware of it I hope that your political landscape is changing so some of these things may change for you but in terms of childhood well-being for example in the richest countries UK, Canada and the US do not look very good compared to 29 rich countries UK and Canada are really rather UK and US are really rather unequal Canada ranks slightly better on that we have enormous differences in pay differences in the difference between the top and the bottom of the earnings and I thought I just wanted to draw your attention to what I thought was a really shocking data that came out by case and detail in 2015 in December showing that at least in the US and we hope at the moment not in other countries but we need to be cautious this is the death rate for all cause mortality for middle aged white non-Hispanic men and women and in the last 20 years it's actually going up and it's going up particularly fast in those without college education so I just kind of wanted to end with saying social inequalities are really now have reached almost a tipping point in many countries and it's really important that while we also look at complex medicine and all the extra information that molecular phenotypes will bring we also need to pay attention to this kind of knowledge which we've known about for a long time and actually we probably know how to make things better here so thank you very much that's the end of my talk well thank you for your excellent and comprehensive presentation I'd like to now open things up for questions just a reminder that you can enter your question into the chat window or the blackboard window I think we have time for a few questions I'll start off with one in what ways has the NSH I just lost my there's so many questions that are popping up so in what ways has the NSD helped to inform policy in the UK and what have been the major KT outcomes so it goes right just to give you an example back in as I mentioned in childhood this study really did influence setting up I think it's something else for a vision of pain relief for women in labour because it showed that women in labour who were having children and babies that however didn't get pain relief and regulations were changed so it's all the way through life it actually helped develop comprehensive education because it showed how bright children from poor backgrounds didn't have the same chance of getting into what was the selective education system in their childhood and so all the way through I don't have time to give all the details and there's a brochure on our website which talks about the timeline of some of the policy things that the study's been involved in I probably should just mention about in terms of aging I mean on the knowledge transfer side there are things where you can link and actually show a specific policy intervention like I've just described for pain relief but there's also the importance of knowledge transfer which is about making sure that the overall importance for example of a good start to life for children what are all the different long term effects if children don't have a good start to life so a lot of policy documents now come in the UK with a life course approach and I'm not saying it's easy to make it's not like you're making a drug I mean when we get to the omics maybe we will be making intermediate markers and drugable targets but there are certainly we at different times when there is political will around these data have influenced how short start programs in for example like the UCS short start programs in the UK and such like there's a whole range can I also refer you to a document that will be on the British Medical Association website I think very soon where they are giving a they did a report in 2013 about child health which is very policy orientated and we were asked to update a chapter on the long term effects and that's going up on the website and it has recommendations it also has recommendations from many other chapters as well so in terms of child health that I think is a good link and then I guess one of the couple of other things just one of the things this shows you too is the importance of looking at monitoring individuals in terms of their change not necessarily just whether people have reached a high threshold but whether people are changing fast in their function for example in the wrong direction why is it that we say in the UK one problem at a time when you're at the GP surgery when we know that people over the age of 55 have several problems usually that are interacting at a time so there's quite a lot of work being done to kind of to see whether these measures of function for example can also be used in assessments for to help clinicians and their patients decide in terms of what treatments that they will be able to benefit from depending on how frail or less frail they are so this is going on in a wider context and we're just feeding into those debates so those are just a few things to kick off great and I'm cognizant of the time as well but I'm wondering if you might have a few more minutes to address a couple of additional questions there's a lot of real interest in your talk which is wonderful I'm not fine I'm firing because I was up at five this morning which is not good okay just a few questions okay so how might post war rationing have affected this cohort well to try and keep that brief it's very hard to show diet affect anything my experience from working with nutritional epidemiologists and but so because it's so confounded people's dietary exposures are so confounded but it did affect the cohort in the sense that this is a cohort that grew up until the early fifties on rationing and things would deration I mean there was rationing going on in 53 I think so they actually were not there was that was one of the reasons for this obesity as children and in fact if anything there's a kind of undernourished group and this stunted group and in many of the epidemiological associations people see you would talk of what I would say trouble at both ends of the spectrum so if you're talking about weight there's trouble if you're underweight and there's trouble if you're overweight and obese or obese so this cohort had trouble at both ends of the spectrum underweight when there were children there's some vulnerable children and that led into a sort of diabetic sort of links into pre-diabetes or diabetes and also this overweight and obese which I've talked about a lot so I won't talk about again but over time the different cohorts have obviously the obesity's got greater and I guess go back to sorry the diet I just say that we have got some lovely new data out looking at diet in terms of bone health and looking at diet over several periods using reduced right for regression and looking at dietary patterns and those things seem to be coming out with more quite interesting and expected associations with specific kinds of outcomes for example like bones but it's a messy area diet I'm not a diet I'm not a new diet okay great maybe I'll try one more kind of a methodologic question have you observed differential losses to follow up related to early life socio-economic position in the data that you've worked with yes interestingly when there were children it actually went the other way in that after the war there was quite a lot of social mobility of the non-manual classes in fact we had very little attrition during childhood but the attrition we had was not in the manual classes so much we have had more differential attrition in adult life in people who for example have severe psychiatric disorders who tend to be in lower social services and in some of the and in the less educated groups for some of the measures because they're flagged on our cancer and death registrations for example we can actually look to see the people who dropped out of the study whether they were for example more likely to die which they are and actually there's lots of evidence that if you want to stay healthy you should enter a cohort study because people who stay in the study tend to do actually rather well but what's very nice is as we go on we know quite a lot about these people as they drop out which is quite different from when you start a study like a Biobank or a study in old age where you go out and you know we were having 95% response rates all through childhood for example in adult life in the new cohort studies you might only get response rates I don't know 50% some of the Biobanks are like 5% so they're not really into representativeness they're looking at associations but you don't know who you haven't got generally at the very most you might have a sample where you know a little bit about them but here we can actually take account of the characteristics of the people who dropped out either because they died earlier or because they decided to completely withdraw from the study which is about 15% of the cohort over those 70 years so it's still quite a small amount great particularly heartening to hear this talk with the CLSA just starting our first follow up we're really getting excited to have our longitudinal data as well but I wanted to thank you on behalf of the CLSA and all the attendees of the webinar for your excellent presentation there have been many thank yous in the chat as well as some requests for your slides if you would be willing to make them available we especially appreciate your participation in the CLSA webinar series and really kicking our 2016 season off with the bang our next webinar is scheduled for February 23 at 12 noon with Dr. A.J. Agrawal and he will be presenting the challenge of cancer in middle income countries in aging populations Mexico as a case study registration is now open and I want to thank you again for attending today's presentation and again thank you very much Professor Coot okay thank you very much thank you