Okay. Welcome back. This is Module F of the seventh week, Unit 7 of the class, and this is the last regular module for Unit Number 7. And in this module, what I want to do is just give you a flavor for ongoing research on the genetics of aging. Obviously, something like the genetics of aging is a very active area of research. So there's a lot of research being done. And in the time I have with you here in this module, I can only touch upon some of the relevant areas, it, with respect to genetics of aging. It's a difficult area for behavioral geneticists to do research as compared to other stages of life because it's more difficult to ascertain the genetically informative samples, twin samples in, in late life than it is in earlier life. Nonetheless, there are good research studies in this area. In fact I'd like to think I've contributed to some of the good research. I do work in this area, mostly at a university in Denmark. And so, what I'm going to try to do here in this module is really just touch on three questions that I've been interested throughout my career, in doing research on, behavioral aspects of aging, to try to give you a sense for research in this area. The first, do twins become more or less similar as they get older? The second is, what do we know from twin studies about the importance of genetic factors to late-onset disorders, that have a behavior component to them? And then finally, how important are genetic factors to the way we age, to individual differences in aging? Let's start with that first question. Do twins become more or less similar as they get older? Now, we saw earlier in this week in module, I'm sorry, in unit seven, we saw, we, we, we looked at research that investigated the transition from adolescence to early adulthood. And one of the, I think more interesting behavioral genetic findings from that particular, developmental transition is that genetic factors appear to become more important as we go from living together with our relatives, to setting out on our own. What happens, though, after that? After we've attained adulthood? And then maturity and later late life. Various researchers have hypothesizes, in adulthood, going from adulthood to middle, middle age to late life that rather than genetic factors become more important, they actually maybe become less important. And that, that environmental factors wold become more important as we get older. And the basic reason for hypothesizing that is the notion that over our lifetime, we have, there's a cumulative impact of our experiences. So, the longer we live, the greater that cumulative impact because we just add more opportunities to have psychologically forming experiences. Well, what do the data show on this? I'm just going to give you a couple examples but I think it's fairly representative. This is a study I've been involved in here with actually a student of mine, Sandell Palin where she looked at, mm, in this case just monozygotic twin similarity across middle age to late life, in various different cognitive abilities. And what's plotted here is the monozygotic twin correlation. And I think hopefully what you see in the pattern here is that overwhelmingly, it looks like the monozygotic twin correlation is relatively stable. That is, there's really no strong evidence that it's declining, nor is there much evidence that it's increasing, that it appears to be the case that monozygotic twins don't decrease in similarity, at least in these domains of functioning, as they get older, even into their 70s. Another trait is the study that I actually was involved in. In Denmark where these are Danish twins. Again, it's only the twin correlation for monozygotic twins. In this case it's how strong you are, a measure of your strength grip strength in this case. And again I, what's plotted here is for both men and women the, the monozygotic twin correlation. Grip strength itself changes with time. You get weaker as you get older. But what doesn't appear to change much is monozygotic twin similarity. How do we ex, explain the stability of monozygotic twin similarity in the face, that these traits are actually changing over time, something like grip strength. Grip strength is definitely declining. The hypothesis that most behavioral geneticists advance to explain the stability of these correlations, is that we continue to construct our environments in a way that allows us, or reinforces, or complements our underlying genetic dispositions. And to the extent we're able to do that, we're able to affect a stability of genetic influences throughout most of our adult lifespan. The second question I want to touch on, and I'm going to do this rather briefly, just with one slide, is well, as people have done twin studies of late onset disorders, do we see the same pattern of results that we saw with early onset disorders? Things like schizophrenia, bipolar disorder, depression, ADHD. And, if you recall back to unit, I believe it was, two, in this course, I told you the very general pattern of results. If you look at twin studies of early onset disorders, is that monozygotic twins are more similar than dizygotic twins. But monozygotic twins are not perfectly similar. The greater monozygotic than dizygotic twin similarity, of course, reflecting genetic influences, the lack of perfect similarity among MZ twins reflecting the importance of the environment, the non-shared environment. Well, what about late onset disorders? Does the same pattern hold? Here's three important late onset disorders, two, two neurologically degenerative disorders, Parkinson and Alzheimer disease. And the third is age related Macular Degeneration. In the case of Parkinson and Alzheimer disease, the, the investigators reported that concordances from monozygotic, which is in blue, and dizygotic, which is in red, they reported them separately for men and women, and they did not do that with respect to Macular Degeneration. The results don't look that different between the men and the women, so I won't comment on those. But do we see the same general pattern that we saw in earlier life? Of course we only have three disorders here, so it's hard to draw real strong conclusions. But I think one of the things that, to me at least that's striking about research in this area is that there seems to be quite a diversity of genetic influence here. For something like Alzheimer disease the genetic influence appears to be rather strong. For Parkinson disease in contrast, the genetic influence, if there is one, seems to be rather weak and Macular Degeneration appears to be somewhere in between the two. And indeed if we did a biometric, or these investigators that published these studies did do a biometric analysis of these concordance rates. What they report is given here and is consistent with that characterization I just gave you, that it appears that Alzheimer disease, Alzheimer dementia is highly heritable. Parkinson's disease is at best weakly heritable. The heritability estimate here only being on an order of about 10%, where as macular degener, age related Macular Degeneration is somewhere intermediate between the two. [SOUND] The third question, to what extent do genetic factors contribute to how we age? Well, before we can answer that question we have to define what we mean by age. How do we measure how we age? And how we go about doing a study to investigate how we age? Well, presumably aging is something that you follow a person over his or her lifetime and you observe a decline in function, that their muscle strength is declining, or that they have less memory capability. Now of course, following someone over their lifetime is a very challenging thing to do. You might have to follow someone over 50 years and a single investigator can't do that. There are very, very few studies like that. There are a couple, but they're very few. Rather than look at those few studies, what I want to do is look at an alternative way of defining aging. A way that demographers prefer, the, the, the, their favorite phenotype for defining aging, aging and that is simply how long you live. Now, that might not be the most behavioral trait. Although you could argue it's very behaviorally relevant. But it's at least a trait that we can measure well and it's a trait that most people are very interested in. Very early in my career I actually did a twin study of life span. And the results of that twin study are, are reported here. And actually I was really surprised, this is a study I did in the early 1990s and this actually, the data here comes from a, a paper published in science in the late 1990s by Caleb Finch, a very well known gerontologists at USC in LA. And what's reported here is, the heritability estimate that we observed in the rather large sample of Danish twins, only about 20, 25%, much smaller than I think most people would have imagined. But actually, if you look at other species, they also indicate that genetic factors appear to be important to how long individuals in those species live but maybe not as important as we thought. Maybe they're only accounting for 20, 25%, 30% of individual differences in lifespan. Now, I was surprised by that and, and maybe you're surprised as well. Most of us have, have heard the adage that if you want to live long, choose your parents well. We think of genetics being very important to aging. So how do we explain these data relative to our general belief that genetics is very important to how long we live? Well, maybe we can gain some insight from a person that I've long been interested in, the person who has been documented to have lived longest among humans. A French woman named Jeanne Calment. Jeanne Calment lived over 120 years, it's absolutely amazing. 122 years she lived. Here you can see a picture of her on her 121st birthday and she's looking pretty good at 121 there. Well did we get any insights to aging in studying the biography of Jeanne Calment? There's a lot of things that Jeanne Calment did that might have helped her live to be 122 years old. She was mod maybe wealthy's a little bit too strong of a word. But she was bourgeoisie. She was a, a, a upper middle class. Her, her, her, they owned a shop. So she had, she wasn't poor. She didn't have a lot of children. She had one daughter. Sadly, the daughter died I believe in her 30s. So she was deprived of that familiar relationship later in life. And, and we know that actually there is a burden, a reproductive burden to having children. Women who have a lot of children tend on average to die a little bit younger. She was physically active. She she rode her bicycle until she was at least a hundred years old. She started fencing when she was 85, she was a tennis player. Like a good French woman that she was, she drank a, a glass of, I think port wine, in her case, every day, and she followed her doctor's advice to quit smoking at the age of 119. She actually smoked until she was 119. She quit at a hundred, this is a picture of her smoking when she was 117. She she quit because she could no longer see to light her cigarette. And she was a fiercely independent woman. And, and if she couldn't light her own cigarette, she didn't want to smoke anymore. Of course Jeanne Calment is a case study. And case studies can give us insights but they can't prove anything. She didn't live longer because she smoked or because she quit smoking at 119. But there is one reason that I bring up Jeanne Calment in this context. It's if you look at Jeanne Calment's pedigree, it's rather interesting vis-a-vis her long lifespan. Look at her parents. Now remember, Jeanne Calment, she was 120 so she was born in the later half of the 19th century. Her parents would have been born about the mid 19th century. Her dad lived, it's a little bit un, unclear clear how long he lived but he, he lived, clearly, into his 90s. Her mother into her 80s. That was extreme longevity for people born at that time. She had a grandfather that lived into his 90s. That would have been a person born in the early 19th century. She had a brother who's, who was, lived also almost to a hundred, and then she had two other siblings who died in early childhood. What's very distinctive about Jeanne Calment's pedigree is, there seems to be an aggregation of very long-lived individuals. Maybe overall, the, in, in looking at Jeanne Calment's pedigree here, it led gerontologists to speculate that maybe overall, genetics is not that important to how long we live. But it may be a particularly important if you're going to live a long life like Jeanne Calment did. Can we show anything in the twin data to substantiate that? Well, indeed in, in a, in a large study that involved, I forget how many thousand pairs of twins from Norway, Sweden, and Denmark. A researcher from Denmark named Miyako Dembo actually looked at twin similarity for how long you live conditioned on the age at which the twins died. And if we looked at twins where one member of the twin pair died before the age of 60, these are the correlations reported in the table that he found for those twins. And again this is a very large sample size, so the correlations are estimated fairly stably. You can see there's absolutely no twin similarity for how long you live. And actually that kind of makes sense. If you, if you look at the reason why people die before the age 60, the predominant, not the sole, but the predominant causes of death prior to age 60 or things that are largely outside the control of the individual. Things like accidents. When he looked at individuals who survived past 85, like Jeanne Calment, look at the twin correlations. In particular, the monozygotic twin correlations. Now, they're extremely high. Genetic factors may not be important, overall. Because early deaths are primarily due to non-genetic reasons. But if you're going to live a long life, if you're going to live into your 80s, 90s and your 100s, most gerontologists now recognize, in part because of data like this, that genetics is probably very important. [SOUND] So this brings us to the end of the regular part of Unit 7. What did we touch on? First, the distinction between the shared and the non-shared environment. This is a very fundamental distinction that behavioral geneticists make. And the general finding is that for most traits, first of all, for all traits, the environment is clearly important in contributing to individual differences. But for most psychological traits, it's the non-shared rather than shared environment that appears to be important. The second thing is that there are some traits like general cognitive ability, religious, how, how religious you are or your political ideology, where you do find or behavioral geneticists do find shared environmental effects. However, if you look at those shared environmental effects, as individuals get older, the magnitude of those effects diminish. Third, the importance of gene environment correlations. Our environments don't happen to us randomly. We in part shape our experiences. We shape our experiences in two important ways. Our behaviors elicit certain reactions from others, and our, and in, and secondly, we actually choose to participate in certain activities and not in others. Fourth, the, the observation, the mere observations that parents and offspring are similar on some psychological trait is fraught with complexity. We went through parent smoking, or maternal smoking, in child ADHD and tried to unpack that from a behavioral genetic perspective. Distinct, the distinction between interactionism, that in any trait you're thinking about, obviously, to have that trait or to have that characteristic requires both a genotype and an environment versus gene by environment interaction that focuses in on why individual differences exist for a particular phenotype. And then finally I tried to highlight some areas in the genetics of aging. So that brings, brings us to the end of unit seven. There will be a supplemental module on epigenetics and twins, but otherwise this, it brings us to the end of this unit. Thank you.
