Men vs. Women: Who Really Ages Faster?

Introduction to Everything Epigenetics Podcast

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Welcome to the Everything Epigenetics podcast, where we discuss DNA regulation and the insights it can tell you about your health.

Meet Sara Hägg: Her Background and Research Focus

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I’m Hannah Went and I’m the founder of Everything Epigenetics. Today my guest is Sara Hagg.

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We have a very interesting conversation for you. We’re going to actually talk about sex differences and aging.

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So what happens and what is different along a male versus female’s path as they become older?

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We’ll talk about how Sara actually got involved in studying aging and jump right into some of the big ways that men and women age differently.

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We’ll actually even dive into hormones. So how do estrogen and testosterone specifically influence how men and women

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age? Well, talk about what happens on a cellular level, a genetic level and epigenetic level, and even dive into

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metabolic mix and proteomics and the differences with each sex there. The one question I’ve always had when it comes to aging and women

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versus men, is that women generally live longer than men. And why is that so?

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We don’t chunk of our conversation actually dives into this and what we know so far to be true biologically speaking.

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We’ll also talk about age related diseases and the ones that men are prone to versus women,

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and different steps we can take regarding precision medicine that can help us approach aging uniquely for men and women.

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There are also some suggestions that Sara makes regarding these unique biological factors for interventional treatments.

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We end with the one misconception people tend to have about how men and women age differently and the surprising things that she’s learned in her work

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about the differences in aging between men and women. A little bit about my guest today,

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Sara Hagg is an associate professor at Karolinska Institute in Sweden and leads a research group

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that focuses on genetic and molecular epidemiological studies of aging. She has a special interest in markers of biological aging

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and longitudinal associations with age related traits and drug treatments, a topic where she has published widely.

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I hope you all enjoy this amazing episode. And now for my guest, Sara Hagg.

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Welcome to the Everything Epigenetics podcast. I’m super excited to have you today. Thanks for joining. – Thank you.

What Inspired Her to Study Aging and Sex Differences

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Yeah. Just give our listeners a brief introduction to you. I know you’re leading a research group.

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You’re in Sweden. You’re focusing on genetic and molecular epidemiological studies of aging in particular.

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So this talk we’re going to have today is going to be mostly fixed on on aging

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and really understanding the difference between how men and women age. But I want to hear it a little bit from you first.

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How did you get involved in studying aging? So I guess it’s always been an interest for me.

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And then, I came in to do my PhD in more cardiovascular disease.

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And after that I went on to do more work also in dementia related research and starting to do more genetic and biomarkers.

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And, and somehow it all came together, on the topic of aging,

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because it, it was all related to aging, all the things I was doing. So it was a natural continuation to just have them

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focus on biological aging them as well. Yeah. Was there any reason in particular you were drawn to cardiovascular disease

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and dementia? When I think of both of those, I have, I would say a personal connection with both of them.

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Regarding historical events and my family and lifetime. But was there a reason that you chose those two?

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Not really, but when I mean looking in retrospect, I can now see that actually,

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in high school I did this, this work already done on Alzheimer’s disease. So I must have had an interest from the beginning that I kind of forgot.

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But then doing the research, I got into this field and it just felt natural because also I have,

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my training is in molecular biology and computer science. So that kind of also has always driven

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my interest in biology and knowing biological mechanisms. So then studying diseases of aging and having an interest

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in biology and genetics. And it was a natural way to continue my research into biology of aging,

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I would say. Sure, sure. And you have all of these age related diseases, right?

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So as you you’re studying one from or you’re going from one to the other, you’re probably seen you’re probably noticing these same trends and themes.

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So you kind of took it over or under that broader just aging research in general and looking at different biomarkers of aging.

5:04

So it’s super interesting. I want to break it down a little bit further because as I mentioned, studying aging can be just very broad.

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So how do we actually start to dive into some of this science. And I know you’re interested in

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how men and women age particularly. Could you give us a little bit more information and set the stage on how we age differently?

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And then secondarily to that, really, are there any things that are unique to each that stand out to you?

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I’m sure there are. As you’re go through this in detail. Absolutely. So I mean,

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for most of the studies that we’ve been conducting and then doing, epidemiological studies on large cohort data,

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we have a lot of large cohorts in Sweden. So really nice materials to work on. It turned out that more and more of the analysis

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we did actually had sex specific effect. So whenever we do,

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something now, we always present data also separately, and men and women. And I think that should be done

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basically in all research where it is possible even in animal work. So it kind of started this interest.

6:15

And then together with a colleague, I wrote a, review article, Sex-specific Effects in Biological Aging.

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And I would say if you look at any type of biomarker, if you look at the hallmarks

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of aging in the way that you can quantify that in, in humans and, so you have telomeres too.

How Do Men and Women Age Differently?

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You look at epigenetic differences, the histone modifications to etc., mitochondrial at this function,

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it turns out that the more you look into it, it seems to be more clear that there are sex differences

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in all of these different mechanisms that you can measure. And then thinking more and more about this,

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it’s also that whenever you look at the biological data sets, the first three components, principal components that comes out in a

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in, in variability of biological variability in a data set is always the sex specific effect.

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It’s the aging effect. And then perhaps some genetic background. So it’s really one of these fundamental differences that you can see in nature.

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So I think it’s a very and of course the interaction with aging is some very,

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appealing to me here in this research field. Sure, sure. You mentioned there, you’re working with a lot of large cohorts in Sweden

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and really, in all of the studies, would it be accurate to say in all of the studies you now do, you’re looking at sex effects?

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Are you believe they should at least separate the sexes to look at them completely differently,

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because we’re going to find other insights maybe dependent on that. Is that correct and accurate to say? Yeah, absolutely. Yeah.

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And I’m we always present the main effect with the whole cohort. But in everything we do we also have the sex specific effects

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separately or something. Yeah. Is there any reason that you could think of whatsoever that you would just look at

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everything together, like is there there any exception that you could think of or you’re just saying right now, hey, to any researchers listening here,

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this is how we should proceed with science in the aging field. Or this is my my specific request because, yeah, you think,

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I’m not saying it would be easy, but you have all of the outcomes from a specific research study. Let’s just start disaggregated and break it down a little bit further.

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Right? I mean, of course, that if you pull everything together, you will see

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that, you know, the broad picture, you will see the main effect. And that’s always what you present first, because it’s also a power issue

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that you want to have many samples together pull together as possible. But that said, I think it it doesn’t cost much to do

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the separate analysis in men and women once you have that pull data together. So I think it should always be presented.

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And also for the reason that later on, even if we have power problems in smaller

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cohorts, when you start to separate in men and women and maybe different age groups, etc., you can always think about the future scenario

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where you want to do a meta analysis of specific research questions across studies. And then of course you have to have the separate estimates as well.

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So I think it’s also important in future perspective that

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we present these data. I mean they could be in a in a supplementary table. Doesn’t necessarily have to be the but it’s so easy to do it

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I think for for animal research is it’s much more complicated obviously. But even there once people start to do it, they usually find differences

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in the female and male mice, for example. Yeah, that would make a lot of sense too,

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especially with your work as you’re going back and you’re wanting to do really large review papers, right? Or trying to

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really gather as many data points as possible. Just having that as a baseline, I think would help expand your work even further.

The Role of Hormones: Estrogen, Testosterone, and Aging

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So that’s definitely understood. And, you know, excuse me, we hear a lot about hormones, of course, in aging.

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I just saw looking at my Google alerts, I get, you know, emails with epigenetics, epigenetic aging, aging biology,

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biomarkers of aging and all of the above, that there are, you know, all of these hormone clocks being created as well.

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So that’s recently become, more, more prevalent. But can you talk a little bit about how estrogen and testosterone

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specifically influence how men and women age, what have you found there?

10:38

Yeah. So of course, this is an area where there is a big difference in men and women. And this is, of course, the whole

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that starting already in utero when there is, you know, testosterone driving a lot of different mechanisms in men etc..

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But for women, up until menopause, the estrogens are really important because they are protective in many ways

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for cardiometabolic outcomes and many other outcomes related to aging. So it’s a really strong link, with aging.

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So as long as you have high estrogen levels, you are protected from many diseases.

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And it also helps you, in many way, I think interactions with,

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with a lot of functions related to like both cellular maintenance systems and also functional systems.

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And once you reach menopause and these estrogen levels and other hormones start to decline, there is a big shift in aging.

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So for women, this is really like this dramatic moment. Or, you know, maybe it’s not just one moment.

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It can can actually be anything from one year to ten years or whatever this transition period.

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But there is a remarkable difference before and after, and also

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related to aging. So after that period, once you reach menopause,

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you actually in many women tend to have more similar profiles in terms of risk for different diseases as men.

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So it’s like they are protected. And then once they get to this level, they start to decline much faster

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in many of the functions, of the yeah, cellular mechanisms that are,

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we want to maintain, as long as possible, but, but after, menopause, then

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these mechanisms are more similar to what we see in men. Whereas in men then we have them.

12:35

Yeah. Anthropos, which is a similar event, but it’s not this clear transition,

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as it is in women because, basically testosterone levels, I think on average, they decline from adulthood.

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They decline by 1% yearly. So it’s a continuous phase.

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So it’s not really clear when the men enter andropause and also I mean, they still can reproduce

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because they still have their sperm production, even if they have low testosterone levels, etc..

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So it’s not really comparable. But some of the men also experience problems with andropause and could have

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similar manifestations of symptoms and clinical signs as women have, although it’s not as common, but it does exist.

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So absolutely that there is some similarities there as well. Oh, there’s so much information to dive into there.

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It’s like you open this black box, right? I kind of my follow up question for you, Sara, after that is would you be,

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I guess, an advocate then or even recommend, trying to delay menopause when it comes to women

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with estrogen supplementation or what have you, I know there’s a lot of connections there with, you know, going through menopause

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and seeing a lot of, acceleration within these biological age biomarkers.

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And I guess even that the andropause again, that’s something I’m less familiar with. You don’t hear that talked about as often, but maybe any type of therapies

Why Do Women Live Longer Than Men?

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or interventions that we can do to help slow that down as well. So I mean I know now it’s getting popular for men in this,

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you know, middle age range to also start to take testosterone levels. I think that is less known.

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But the research on hormone replacement therapy in assess

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estrogen levels for women, that’s at least a bit more evidence.

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That type of a and also studies on that. So I think that yes, it may be possible

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and I think this is really interesting, future research field as well. We don’t have enough information. We need to know more.

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Is it possible to use these HRT replacements and actually prolong them?

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This, you know, functional phase in women predominant for them so that we would maintain function longer and also prolong a healthy life with that.

15:01

So what is known I think there seems to be a little bit of evidence this. But if you do it, you need to start early or you need to start at the right time.

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You cannot start too late because if you’re already on your transition down, declining in these hormonal levels,

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maybe there is also already been transition in a lot of the mechanisms. So then it’s not beneficial to the same degree anymore.

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So you have to start early when you still are basically having maintained a cellular function.

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But when you already when I mean, I think the timing is very difficult because you have

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you will not start too early when you know, you still have your estrogen levels as normal, but not too late either,

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because then you can see that you don’t get the same benefit. Yeah. And I also think that it’s very interesting talking to a lot of clinicians

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in this area where they say that, well, we have this women, they come in and they get this treatment that they’ve had it for 10, 20 years.

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And, you know, they don’t have gray hair. They look all, you know, living and blooming and and it’s just amazing.

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Why don’t everyone take this? And, and I guess the answer is, I don’t know.

16:12

We don’t know. We don’t have enough evidence yet. So there is definitely more studies needed here. Yeah, definitely.

16:17

And that’s why I work with, you know, day in and day out as a lot of these healthcare providers in the cash pay medicine space who are treating healthy people,

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they’re more of your anti-aging, functional interventional, providers. And I would say a lot of them are using the hormone

16:30

replacement therapy on their patients as well. So it’s been really interesting to see that change starting to happen.

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Even, you know, as my parents get older, my mother and my stepfather wanting to become healthier.

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And again, their hormone levels are probably declining, but it’s something you just don’t see.

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You don’t see a lot of attention given to that area when they’re just going to their general practitioner offices as well.

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And, Sara, if you could just on average give like an age for, for women,

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maybe men two when do we really start to see those estrogen levels start to decline pretty rapidly?

17:04

Is there like a window I know it’s very dependent on the person, but is there a particular window you could give by chance?

17:11

I think the mean age of menopause in women is around 55 years.

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At least in maybe that’s mostly based on European ancestry populations as well. Yeah, but that’s, the number I have in my head.

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But, you know, we can, as you say, can vary very much. It can be, you know, starting already in the 40.

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And, you know, some people it doesn’t happen until they’re 60. So it’s really, really variable, of course.

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And also the period that you experience all of these symptoms, problem is also… And you’re

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talking about estrogen supplementation sometime years before that. To really start to optimize your levels before going through menopause as.

17:53

Well I guess so. But the problem is that it’s not really tested. Even if you go to your GP, it’s like they don’t

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they asked for your symptoms and then oh, but you’re fine. It’s good. It’s no problem.

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And you know, it’s like I think that we also have this misconception that we used to believe that having these type of hormone

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replacement therapy would lead to increased cardiovascular mortality because of some of the earlier studies.

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And now we have better treatment we’ve seen, but that’s not really the case anymore.

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So it’s also a change in mind in terms of the evidence that we have, I think.

18:29

Yeah. Yeah, definitely. It’s super interesting to talk about and to ponder over. I think hopefully within, you know, my lifetime,

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I’d love to see some type of biomarker test for menopause. Or perimenopause to be able to tell a woman, hey, you should prepare for this

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or you know, intervene this way, this is how long it’s going to last. This is probably what you would expect to feel just so we can start to normalize that a little bit.

18:53

So I think there are some research groups working on that. But I’d absolutely love to see that. Yeah yeah I agree.

19:00

One question I’ve this is actually come up a lot, and I don’t think I’ve ever had an answer for this.

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I think you out of all people, I’m gonna put the pressure on you. Sara might be able to answer this with your expertise in your background.

19:13

We know that just women generally live longer than men, right?

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They live these longer, healthier lives. Men have usually accelerated biological aging.

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With almost any biological age biomarker you use. Do we know why that is?

Cellular and Epigenetic Differences in Male vs. Female Aging

19:31

I really have tried to do some searching and some digging, and I haven’t found an answer, but I’d love to hear from you.

19:37

Obviously, everything we were talking about, the hormones probably play a role, but what do you think?

19:42

Yeah, it’s a very interesting question, and I think,

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I mean, you can do it from different perspectives. I mean, to start with, we have them and the sex specific paradox.

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So that’s, you know, we have certain areas like the biomarkers of aging, the cellular markers where women are better off,

20:02

so we can see them, that women have better cellular maintenance system. So then of course, people say, oh, it’s the telomeres

20:08

or it’s the epigenetics or it’s all of this. And this explains why women live longer. I don’t think that is just one explanation.

20:14

I think it’s much more complex than that. I mean, we also have the different the sex chromosomes

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and regulation of these genes, etc.. But if we would take one step up and look at it

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from a theoretical point of view, I mean, evolution, in some way men

20:34

are more susceptible to be fixed early in life because they need to, you know, be the predominant male that can reproduce,

20:43

and produce offspring, whereas women are a little bit,

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you know, a little bit more careful because we need to be the one that provides support offspring for a longer period of time.

20:59

So just thinking about the biological habit,

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human beings that we are, it’s really a difference in the way that nature tried to modify this.

21:11

And one example of this is that, if we look at, out there is not so many differences

21:20

in terms of, you know, genes for men and women. But there are some differences in anthropometric.

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So we can see that there are sex specific effects the way that we have, genetic variants coding for height, for example.

21:35

So how tall we get, which is one of these things that men, they like to be tall because, you know, the taller they are, the more fit,

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the more you know it will be to find someone to produce an offspring. Whereas women, we don’t want you tall individuals,

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because if we have a very tall mate, we may get offspring that are very big and then we can’t give birth to them.

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That’s a risk. So women try to have put the balance on that. So that’s actually where we see a sex, sexual dimorphism effect on these things.

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So I think that’s really interesting. So it also speaks to this fact that there is a way that,

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you know, nature is trying to balancing this fitness versus survival effect,

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where we have different pressures on us, as men and women.

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So in that way, I think it’s natural to think that women have better maintain cellular maintenance system

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because that’s what we need to to survive longer, to be able to repair and restore and, you know, keep our cellular functions intact.

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Whereas men, they they put a little bit more risk in to being fit early in life

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with a cost that later in life they don’t have the same, possibility for repair.

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And in the, in these cellular functions. So I think that there is a fundamental difference, here that is

22:59

somehow, going through all of these complex mechanisms that happens in life.

23:05

And the differences between men and women is somewhat, perhaps, a result of this.

23:13

That’s interesting. I will tell you, that’s the best answer that I’ve gotten so I can take it.

23:19

No, I think it makes a lot of sense. It’s like you mentioned, it’s this underlying evolutionary effect.

23:25

Almost, right? Astime has gone on, and my mind actually goes

23:31

to more of the future if we’ll ever see this change. Maybe not.

23:36

Men living longer than women, but I would say I never, never want to say never. But it may be leveling out a little bit more or,

23:46

and the reason I say that is because now we’re starting to see a lot more women, you know, go through the IVF process, right?

23:53

Even on their own or there’s just a lot of changes, I think happening in the world with just overall reproductive health.

The Impact of Stress, Diet, and Environment on Aging

24:01

So I’m wondering if we’ll start to see kind of evolutionary changes, even down to the cellular level as well.

24:06

It’ll be interesting to follow that. Yeah, I think that would be interesting. We don’t know how that will affect. Yeah.

24:12

But I also think that one thing that is in support of this is that you can see in societies where, you know, the gaps

24:20

between men and women in terms of them, you know, income or in education,

24:26

all of these social factors where the gap is, is getting smaller. Then also the survival difference is getting smaller.

24:34

So it speaks to the fact that there is some some sort of social context there that could perhaps help to, to close the also the survival gap.

24:42

But yeah, I don’t know how all of these new, treatments and the IVF, and all of those things

24:49

will actually influence and change our evolution in some way. Yeah, yeah, I didn’t even think about

24:54

the social aspect of it all, but it’s all all in our playing together. You brought this up a couple times, Sara.

25:00

Actually, I’m curious about just the role of genetics here, too. Right? We talked about having different chromosomes, our sex chromosomes.

25:07

How much does our DNA, if you want to look at that? Almost as, like an aging biomarker of some sort,

25:14

influence the differences between men and women’s aging.

25:20

Well, most of that is in, in the sex chromosomes, I would say, because,

25:26

I mean, overall in aging, our genes are, surprisingly,

25:33

have a, have a quite low effect on the overall survival in life. So, I mean, the environmental contribution is much bigger,

25:42

at least if we speak about general populations. So also in the sex specific effects, I mean, we haven’t seen much,

25:50

sex difference in genetic variants in, in all the other out

25:55

to some say all the other chromosomes, beyond the sex chromosome. So the one that I brought up in

26:04

the difference in height, genetic variants that’s one example, but there aren’t actually that many.

26:11

So very few. Yeah. It’s going to be more about those the epigenetic interactions. Right. I think it

26:16

must be about regulation and how the hormones interact with the regulation processes in the bodies, for example, because we’re

26:22

we’re more or less born with the same genes basically. Yeah. Exactly, right? And then, you know, so we talked a little bit about genetics.

26:30

You gave that really good example of the height differences. What about just epigenetics in general?

26:35

I know that’s a really, really broad question. I can’t not bring it up with my my podcast.

26:40

We’re named Everything Epigenetic. So you have your lifestyle choices. I mean your diet, your exercise, your sleep, your stress, all of those,

26:49

are I mean, it’s this is a hard question to ask, almost because it’s very dependent just on the individual person,

26:56

you know, regardless of whether you’re a male versus female. But are there any lines that can be drawn that say, you know, epigenetic?

27:02

We’re seeing maybe something a little bit more favorable or less favorable with male versus female?

27:09

Yeah. I mean, you’re absolutely right that there are so many things that that influence. But on on all levels, when we look at DNA methylation

27:17

or histones or whatever, we see that there are differences in men and women. And we have done a lot of studies done, of course, with the, you know, the clocks.

27:25

And if you also look at those levels when you age, you know, you see the sex difference again here that, that women tend to have overall

27:35

a better maintained phenotype plot, compared to men. And that we see that basically across all different types of phenotype clocks.

27:43

So there is absolutely there’s a differences, on the epigenome.

27:48

And I would say it’s you would probably find it regardless of what you’re looking at.

27:56

That’s my guess. But as you say, of course, then it’s the next level that, you know, in biological variation depends on so many things.

28:03

So of course the individual variability is still larger, I would say, so…

28:08

I mean, we speak in general terms, but of course that could be one woman that looks completely different.

28:13

And then you compare it to that man that looks more like this group of women or whatever. I mean, you can always find exceptions to that.

28:20

Sure, sure. No, that’s that’s good to know. And, you know, we’ve talked a little bit about genetics and epigenetics.

28:25

You talked about, different epigenetic modifications, DNA methylation, histomodification etc..

28:31

In telomere length as well. There may have been a couple others that you mentioned, but in terms of the studies that you’re doing, what other biomarkers are showing

28:39

us, these aging differences between men and women. And, you know, can you just expand on that a little bit like,

28:44

how much can we actually see from those markers even, What’s your favorite to look at? Like when you perform a study, are you including all these biomarkers?

28:54

I know cost can be a really large factor as well. But even if you want to walk us through one of your studies and some of the interesting findings there.

Age-Related Diseases: Which Are More Common in Men vs. Women?

29:01

Right? So I think one of the new things we’re doing now is proteomics. And also metabolomics has been ongoing for

29:08

for some time and doing all of these specific clocks. And here we can see—

29:13

so we have one project now that we’re doing of course like a lot of other groups are doing this organ specific clocks.

29:19

And but we’re doing it on Swedish samples. And there we can see that, of course

29:26

there are proteins that are sex specific, and you can also them develop at organ-specific clocks for men and women separately.

29:34

And you will have a little bit different results. So I would say that you can you can see this on on all of these,

29:39

you know, molecular markers, biomarkers. But another type of marker that we’re looking at is, functional markers.

29:48

So we in the cohorts we have, we try to assess as much as possible. So we also look at, you know,

29:53

muscle strength in different ways because we have a lung capacity. So you get to the aerobic capacity a little bit.

29:59

And also you know grip strength and walking speed and things like that.

30:05

And here, of course, we know that men perform better than women because, you know, they are they are bigger, taller,

30:10

they have larger hearts and bigger volumes in their lungs, etc..

30:15

So they are overall stronger and perform better in these markers. Because they, they put their, you know, they put their energy on the fitness.

30:24

So, so it makes sense that that’s what we see. But yeah.

30:30

So I think that’s also another area where it’s interesting. And then of course we can again see the sex paradox because,

30:36

if women are better off in, in the cellular level, then when we move to the functional levels,

30:42

we see much better results from men compared to women here. Yeah. Yeah. Exactly.

30:47

Yeah. That’s super interesting. You know. Yeah. The space that I am in, obviously my company Tru Diagnostic,

30:54

we offer the Symphony commercially, created from Dr. Morgan Levine and Albert Higgins-Chen,

31:00

Raghav Sehgal, and that’s the agent of the 11 different organ systems. But they’re not separated based on sex. And I want to go back now

31:06

and separate all of them and rerun them because, like you mentioned, just that functional measurement of like, you know, we have the

31:13

the heart age, the musculoskeletal age, the metabolic age, right? They’re going to have you’re

31:18

you’re going to have different trends in men versus women. Again, we run

31:24

we run the algorithms on each of the individuals. And then we’ll compare them to the population based off of, you know, female versus male, but you’re not running the clock.

31:31

The clock wasn’t created just on men or just on females. So you have my my wheels turning and spinning on how to make these predictors even better.

31:41

Yeah. Yeah. So I mean it’s always you have to make these choices all, all the time. Like should you prioritize a bigger sample or should you get

31:49

to this specific sex effect or it’s like all of these choices. So yeah, in different ways you can do it.

31:57

Exactly. It’s it’s hard to there’s a hormone age on there that unfortunately they they were only able to use IGF one in DHEA,

32:04

for the creation of the, the algorithm because that’s all that the Biobanks have. Right. And it doesn’t make it any less predictive of the diseases

32:11

because they validated it in a really nice way. But, we also understand the limitations of it, where it’s

32:16

not grabbing estrogen, testosterone, progesterone is other hormone markers too. So, hopefully we’ll get some more

32:23

biomarker data and be able to make that a better predictor. Another question for you.

32:30

So you you have these these biological, you have these biomarkers of aging per se.

32:36

Right. What about then coming back to the beginning of our conversation, these specific age related diseases, right?

32:43

We know that there are certain ones that men are more prone to and women are prone to. So what can, can,

32:50

what might that tell us about how each gender ages? Do you look at that in some of your studies?

32:56

And then can, you know, we intervene based on that. Yeah. Yes we do. We try to I mean, so there are different things there is this,

How Biomarkers Help Predict Aging and Disease Risk

33:04

you know, just looking at statistics, how many men and women have this type of disease, etc..

33:11

And then of course, you can also look at, okay, so what’s the risk of getting that disease

33:17

given that you’re a man or a woman, depending on if you look at the biomarker for example, that’s an exposure. So there are different ways of looking at it. But

33:25

what I can say is that, we know that there are differences. So men usually have more of the cancer diseases.

33:33

I mean, cancer is of course a broad spectrum of different cancers

33:40

and reproductive cancers, etc., but they’re different in different sexes. Obviously.

33:46

But then women have more of the, the women tend to respond better to, you know, to vaccines and have a higher,

33:55

you know, immune function in general, in terms of response to pathogens, etc..

34:01

But that also leads to a bigger risk of having out immune diseases, though in women, we can see that, that happens at least before menopause.

34:10

They have high risk for that, whereas men then have more of an, immune or senescence and in,

34:19

maybe the same inflammation, aging problems. So, so there are differences there. And and of course, we know dementia.

34:26

It’s much more prevalent in women. And that could be many reason for that. So absolutely, there are differences here.

34:32

And you know, we know many of these, you know, the hallmarks of aging. Many of the processes here have quite, overlapping functions

34:41

with hallmarks of aging or hallmarks of cardiovascular disease. And they’re all also hallmarks of neurological disorders now.

34:48

So so all of these things also speak to maybe a little bit of sex specific

34:53

mechanisms as well that’s underlying these different diseases. Yeah.

34:58

And and talking about all of the differences that we do know and that are apparent today.

35:04

Do you think a lot of these again the cash pay medicine space, more of these integrative holistic

35:11

based clinics will start to take more of an approach. Because we think probably men and women should be thinking

35:17

about aging differently, right? Regarding their health and vitality, I think we do see a lot of clinics

35:24

offering, you know, women’s health or men’s health. But do you see your work really starting to maybe dig into more of that

35:32

interventional space to be able to say, hey, this is how you’re aging? This is how we should, of course, treat each individual, but especially just starting with each sex.

35:42

Yeah, absolutely, I completely agree. I mean, starting with the different sexes is like

35:47

the first thing you can do in precision medicine them. But, I mean, for one thing, a lot of women are still not included

35:54

in clinical trials. So we don’t know exactly that they respond the same way to men

35:59

for different treatment, and in different age groups, etc.. So that is one thing.

36:04

And also women in general, when we give advice on, on lifestyle factors and changes on that, there is also a big difference there.

36:13

So, how men and women, both in terms of diet, maybe what they would benefit from

36:22

and also in physical activity because they have the difference in functional performance, they also respond differently to different,

36:30

physical activity, strength training or, or more cardio metabolic fitness training.

36:35

So it’s all of these differences. We could absolutely do better. I was just looking at the W.H.O.,

36:43

you know, the guidelines for dietary intake and for exercise, and there are absolutely no, specific guidelines for men and women.

36:51

It’s all, you know, just one, big thing and also for, for older individuals,

36:56

there may be a little bit differences in some of the guidelines, but not clearly enough. So I think we can do much, much better here.

The Future of Precision Medicine in Aging

37:04

Yeah. That really just surprises me. It breaks my heart a little bit, you know, that, that, that that was kind of my,

37:10

my next question as well. Yeah. If there even those recommendations out there, I mean that seems like the bare minimum for like our health as, as a species,

37:19

as, you know, an entire society is to say, we know you two are different. Here’s just some little tweaks or, you know, my new differences

37:27

we may want to make in terms of recommendations, to have better outcomes and to live longer. So I definitely hope that that changes in, in the future.

37:34

And this kind of aligns with with just that, what’s maybe one misconception or the biggest misconception

37:41

that people tend to have about how men and women age differently. Does anything stick out to you?

37:48

I mean, maybe it’s this thing that you you often read. It’s still like, oh, we found this difference in men and women.

37:54

So it must be the one thing that explains the survival, difference.

37:59

So they always, you know, whenever they find when it was the telomeres, it’s like, oh, this is the whole explanation.

38:04

But I mean, it still amazes me that people can think that it’s really just this one thing.

38:10

I mean, it’s it’s very often with biology, it’s so complex. So I think that it’s it’s not going to be just one single thing that we can

38:19

that will solve the whole thing. It’s much more complex. Complex. So yeah. So maybe on the surface, of course there’s going to be a sex difference.

38:25

Right? We should expect that I would say in every single study, right? If we didn’t, then maybe we’re we’re doing the study wrong.

38:32

But obviously that’s. Yeah. Again, an easy way out. We really have to dive into then.

38:38

Each individual sex, I think a little bit further to start to explain those differences and get closer and closer to the truth.

38:44

So yeah, that that definitely makes sense. And then we’re, we’re getting to the end here as well.

38:50

Sara, what’s one surprising thing you’ve learned in your work about the differences in aging between men and women, or

38:56

just something that, you know, it could even be what you’re most excited about, why you keep coming back to this topic over and over again, and you know

39:04

why you’re dedicating your life’s work to it. Right? So one thing that we haven’t really touched upon is, like the

39:10

the later life, when you get to multimorbidity, you actually have these diseases, symptoms developing and you get frail.

39:18

So in the frailty perspective, there are a lot of differences. So it turns out that there are both

39:23

societal and biological differences in men and women. So men seem to be, you know,

39:30

women outlive men, but to do it with worse health. So they actually have more multimorbidity, being more frail in the end of life

39:39

and for a longer period, them, but they still outlive them. So they do it with this, you know, this six, that we call it in the end of life.

39:49

And I think that that’s really sad. Like men, you know, they they survive being fit all the way to the end.

39:56

And then once they get sick, they just die, basically. I mean, it’s an exaggeration, but I, I wasn’t really aware of the,

Surprising Findings from Sara Hägg’s Research & Closing Thoughts

40:04

you know, the end of life, the, the, the later part of the life where there is a parent sex differences as well, that maybe we can do better

40:12

there as well, I don’t know. Yeah. So that’s surprising to you. That’s something that you’re looking into a little bit more as well because yeah.

40:17

Then as a women it’s like, oh do I really do I really want that. Sure. We live longer but do is it.

40:22

It’s that healthspan versus lifespan. You said six fan type of type of argument. So it’s it’s almost hard to, to think about

40:30

and then are you doing any interventional trials as well right now. Any interventions with any of the cohorts that you’re

40:38

doing to looking at extending lifespan? We don’t. But that’s obviously something I would like to do.

40:46

And I’ve started collaborations with, with some health tech companies in Sweden. So we’re hoping to do that soon, because also part of this is like,

40:56

you know, the whole problem with it, with the health care sector that they, you know, they’re treating go then the old and the sick people.

41:03

But what if we can, you know, put some of that in more into more preventive, health care so we can actually do something early in life.

41:12

So we’re hoping to do some studies of that, and we have some plans, so in the coming years, I really hope to do that.

41:19

Perfect, perfect. Well, I’m so excited to bring your your work to light. And, I can tell you’re just super passionate about it, so I’m excited for what’s to come.

41:28

We’ve come to the end of this amazing podcast, so I do ask all my guests one random question at the end.

41:35

So, all right, if you could be any animal in the world, what would you be and why? Oh, it’s a curve ball.

41:43

Yeah, that’s a good question. I would probably like to be like some sort of bird where you can fly.

41:50

Oh, I think that would be really cool. But maybe you wouldn’t. Well, if you’re bats, then I would live long.

41:55

So maybe maybe a bat. There you go. Well we’ll take it. That’s a that’s a great answer.

42:01

I know I love that answer. And then for anyone who is listening to this podcast who wants to connect with you, obviously they can Google your name,

42:08

they can look at your Google Scholar, all of that good stuff. Do you want to point them in the direction of a lab website or anything else?

42:15

Yeah. So I’m a bit bad with the lab website, but I do have a good profile page on Karolinska Institute that,

42:22

so if you go into https://ki.se/en and Google my name, you, you will find all of that information.

42:28

Perfect. Well thanks so much, Sara. And thanks everyone else for joining us at the Everything Epigenetics podcast.

42:34

Remember, you have control over your epigenetics. So tune in next time to learn how. Thank you. Thank you.