Speaking of Women's Health
The Speaking of Women's Health Podcast is excited to bring you credible women's health information from host and Executive Director, Dr. Holly L. Thacker. Dr. Thacker will interview guest clinicians discussing relevant women's health topics and the latest news and tips.
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Speaking of Women's Health
Anti-Aging Strategies for a Long, Healthy Life
Unlock the secrets of a longer, healthier life with guest Stetson Thacker, PhD, as he sits down with Host Holly Thacker, MD to discuss the fascinating interplay of genetics, exercise and longevity. Listen to discover how physical activity might be the key to adding years to your life.
Explore the frontier of genetic testing and anti-aging supplements with insights from both Dr. Thackers. From foundational health habits to the exciting possibilities of genetic factors in longevity, this episode offers practical wisdom and cutting-edge science for those seeking to enhance their well-being - and lifespan.
Listen to Stetson Thacker, PhD's new podcast Views From Cleve-Mandu and follow him on Substack at stetson.substack.com.
Welcome to the Fit, Healthy and Happy Podcast hosted by Josh and Kyle from Colossus...
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On this episode of Speaking of Women's Health we have a recurring guest. I'm your host, dr Holly Thacker, the Executive Director of Speaking of Women's Health, and I am back in the Sunflower House and joining me on this episode is my son, dr Stetson Thacker. No relation, of course. He is my oldest son. I talk about him all the time. Stetson Thacker no relation, of course he is my oldest son. I talk about him all the time. He was a guest on season one and it was one of our most listened to podcasts in the over 100 plus that we've done. So he joined us back in season one to talk about genetic testing for cancer risk and how our genetics can help with weight loss and how to continue your weight loss resolutions with a few simple tips. So on this podcast we're going to delve into anti-aging in terms of genetics, the biology, the history that we know of the hacks and maybe some potential pitfalls and manipulations to watch out for, since it's really quite a hot topic. So a little bit about Dr Stetson Thacker. He completed his PhD in genomic medicine at Case Western Reserve University and the Cleveland Clinic Lerner College of Medicine under the tutelage of the late great Dr Dr Karis Eng, who unfortunately departed this earth. She was really quite a scientist and trailblazer. So Dr Stetson studied the impact of genetic variation on protein structure and function, as well as clinical traits in a cancer syndrome called P10 hamartoma tumor syndrome, and I certainly have the privilege of seeing many P10 patients in my practice courtesy of oral referrals from Dr Eng and her group.
Speaker 1:Now Stetson has authored several columns on speaking of women's health. He's actually a prolific writer. He published a book on poetry when he was in high school and also was a first author publication which is highly cited in fertility and sterility, from research he did when he was a high school student. Today he is the father of two adorable girls, my granddaughters, who just are so excited to see me. By the way, when I go to their house they squeal, and when they're getting into my car my son wonders why do they like your car seat? I'm like no, they just like coming with Mimi.
Speaker 1:Anyway, stetson's very busy. He works as an associate clinical variant curator for Natara, where he interprets and classifies genetic variants detected by the burgeoning field of molecular diagnostics. And Natara is a global leader in cell-free DNA testing and it's dedicated to oncology, women's health and organ health all things near and dear to our hearts. In his free time he writes on various subjects, which we'll talk about at the end of the podcast, which include cancer, genomics, and his substack is stetsonsubstackcom, and he just started his podcast. I guess he's kind of like his mother in that regard. So, stetson, welcome. Thanks for joining us again with your busy schedule.
Speaker 2:Thanks for having me.
Speaker 1:So I thought it would be really interesting to talk about anti-aging and what are maybe some of the best anti-aging strategies that our listeners might want to be aware of or think about doing.
Speaker 2:Yeah, there's a lot of hype in the space. The longevity space is the term of art we hear now a lot. I think the best way to think about it is from two different perspectives. There's the individual perspective how can I do things to help myself live a more healthy and longer life, which is how most people are thinking about it. And then there's, of course, the population level, the public health level perspective, and what can we do for the the health of the population, to help people have longer life expectancies, lower mortality rates and so on. And so from the individual perspective, there isn't like a ton of things that we know for sure will definitively extend your life. I mean, if we did, they'd be plastered everywhere, everybody would be doing it all the time. We kind of know these sort of generalized health recommendations that we have that are you know, eat healthy, exercise, sleep enough, things like this.
Speaker 1:Things that we focus on on so many of our podcasts, by the way.
Speaker 2:Right, and it's not to say I mean, those are important things that we should focus on, living healthy lives. We know what a healthy lifestyle constitutes and we should focus on those things and of those, probably the most important is exercise. There's a lot of observational data, a little bit of experimental data that shows that people who exercise will really live longer lives. There was a recent observational, there was a longitudinal work that showed that it was following 40-year-olds and they were using these wearable devices to follow their activity and if everyone was as active as the top quarter of the people in the study, they would have five additional life years on average. So it shows you that that's a lot.
Speaker 2:five additional life years, yeah that's a really large effect, if that's truly an effect. Now it's just observational data. It's not necessarily experimental data, though it is longitudinal and it's very well powered, but at the end of the day, we don't know exactly how necessarily. Exercise would be for sure extending life. The idea is that it makes you more functionally healthy. That makes you stronger.
Speaker 2:So it works against the age-related muscle loss that we see in a lot of people, and it's keeping your cardiovascular health, your circulatory health, up and running. Maybe there's some other benefits in the immune system or whatnot, but it seems like the one intervention that people can really work on because a lot of people live sedentary lives is exercise.
Speaker 2:So that's my one recommendation. But then the story's a little bit more complicated from the population level because we've had a lot of success over time already improving life expectancies. Post-industrial revolution people used to live nasty, brutish short lives the the Hobbesian construction there and we've improved that a lot.
Speaker 1:Right like so you would be really old if you were living like 150 years ago, right?
Speaker 1:yes, yeah, that would be and and I would be like non-existent. Yeah, so really, if you look over the last hundred years, there's just been this constant acceleration, but we have really plateaued off and in the last few years life expectancy is starting to dip and in the field I'm in in menopausal hormone therapy. When the Women's Health Initiative was released over 22 years ago and women threw away their hormones which we know and the study itself showed longevity by several years we did see death rates in women lose significant ground, particularly in hysterectomized women. So that was really very devastating. So when you talk about adding five years with exercise, that's really huge and that's what I say. Treating hormone deficiency will give a lot of women just shifting that age aging curve to the right. So why do you think there's country differences In? Like some countries just tend to have more older individuals that live longer and healthier, or older individuals that live longer and healthier.
Speaker 2:So I think embedded in that question is essentially a question about blue zones. So there's this idea that there are areas like, say, sardinia, which is this island in the Mediterranean off of Italy, or Okinawa in Japan, and these areas are alleged to have a high number of centenarians.
Speaker 1:Apparently, people have looked into it, that's people for our listeners that are 100 years or older, right.
Speaker 2:Yes, exactly so, extremely long-lived people. So they've done a little digging into these numbers and it turns out that there's some poor record keeping and so a lot of the cases, and especially like Italy, greece, even in Okinawa, the records for these people that are supposedly alive, these people are not not really there or they didn't really live as long as they, as they said they did or as was recorded. Some of this has to do with sometimes the check keeps coming from the government. If you say this person's still alive, oh, interesting.
Speaker 2:Yes, yes so there's incentive in certain places for people to live quite a long time, at least on paper. The Blue Zone idea has really taken a hit, so I don't really know for sure if we can say. I mean there obviously are differences across geographical regions and life expectancy and I think most of that is explained by economic development for the most part. So if you go to very poor regions, their life expectancy is lower and if you go to very poor regions, their life expectancy is lower and if you go to very developed regions, it's higher and obviously there's some
Speaker 2:differences, but you're when you're talking about, like saying, in america there's lots that is made of the deaths of despair hypothesis, the angus deaton hypothesis he was the economist who won like a noble prize for this work, I believe and they argue there's a huge spike in opiate abuse related deaths or alcohol related deaths in America relative to other advanced nations. There's some quibbling that can be made about this, but that's to some extent a real thing. But the difference that we're talking about is small relative to when we're talking about cross-national differences between wealthy countries and developing countries.
Speaker 1:Well, we're here in the United States of America, which is a very fortunate, wealthy country overall, but we have a lot of obese, unhealthy people, unfortunately, with very high rates of metabolic syndrome and inflammatory conditions that increase everything from heart disease, diabetes to dementia, arthritis and so forth. So sometimes and, oh, of course, cancer is very much linked as well. So I think that there's got to be other factors, like diet, like we always promote the Mediterranean diet and the Italians and the Greeks as having long, long lives.
Speaker 2:So do you think some of that's?
Speaker 1:dietary related or is it their lifestyle? They are more physically active, have more exposure to outside beautiful sun, gorgeous scenery.
Speaker 2:I mean, I think perhaps there's something to it, but it's on the margins and it's small and rates of obesity are quite high across the developed world in general, and even in some less than developed places have fairly high obesity rates. It's surprising. It's really cheap. Calories are really pretty accessible almost everywhere. Obviously, this is not true for some places, but in a lot of places food is not scarce anymore, thanks to some of the revolutions that another Nobel Prize winner, norman Borlaug, made quite a ways ago in terms of agricultural advancements and agricultural technology, of course, the Haber-Bosch process as well, well before that, so very calorically dense food that tastes great.
Speaker 1:You know there's concerns. And then anything that's broken down quickly into simple carbohydrates drives your insulin levels, which makes you hungrier. I always say that's why they give you that delicious free bread at these nice restaurants, because then you're hungry for dessert by the end of the meal, which you're very good at getting dessert. Whether or not you eat bread or not, you have quite the appetite.
Speaker 2:So I do so.
Speaker 1:Peter Attia, who is a physician in the longevity space, this is I know you gave me his book and I'm trying to still slog through it.
Speaker 2:Yes, his book is called Outlive, and so his only advice on nutrition, for example because we're kind of circling the nutrition topic is that it's about energy balance, so the calories in calories out model. We should try our best not to eat more calories than we expend. And then in terms of what we make our diet what can? What comprises our diet? The only portion that's really important to make sure is there is the protein intake. And he's saying that protein intake is especially important as you age because of that age-related muscle loss, age-related strength.
Speaker 1:Yes.
Speaker 2:And that's the functionality that you want to maintain, because when you're losing that functionality, you're more likely to decline more rapidly.
Speaker 1:Yeah, I think that certain healthy foods that are high in protein, whether they're eggs or red meat, unfortunately kind of have been demonized too much, demonized um too much, and so I still think there's a lot we need to understand about um nutritional, uh, genomics, and I do think there's probably different diets that work out better for different people, and we don't really know um to give advice. We just kind of give general advice and I think a lot of times the medical profession doesn't give the best nutritional advice, unfortunately, and and certainly everywhere you go with fast foods and school lunches that aren't that healthy, it's it's like swimming upstream.
Speaker 2:Yep, there are some ancestry related differences in how calories are handled that we're really just beginning to learn about thanks to large genomic sequencing studies and phenotyping studies, which is just looking at the traits, and so we're learning that people who have, say, more ancestry background from hunter-gatherer populations are more thrifty. They make better use of the calories that they take in than people who have more distant ancestry from to hunter-gatherers.
Speaker 2:so obviously, people of like west eurasian ancestry, people of east asian ancestry they're a little bit more distant potentially than than someone who is very recently from or more recently we're talking longer time scales, of course, but more closely related to, say, other hunter-gatherer groups, for example, and so one of the famous cases of this is, of course, the pima indians, which of course, there's some scientific debates about, but there's. There's some pima indians that were in mexico and those in the united states. And the p Pima Indians living in the United States were eating a Western diet, and those that were living in Mexico were eating their ancestral diet. And the Pima Indians eating the Western diet were getting type 2 diabetes in their late teens, early 20s, while those that were in Mexico, living in an ancestral fashion, were completely healthy, for example, so there's definitely ethnic and genetic differences for sure.
Speaker 1:I know that there are some nutritional genetic researchers who are really looking into this researchers who are really looking into this, looking at profiles and dietary substances in terms of things like premenstrual dysphoric disorder and there's so much interest in this nutrigenomics and I know that people can go and have that genetic testing done that tells them, you know, if they're at risk for celiac or if they're at risk for Achilles tendon rupture or maybe if they're more at risk for B12 deficiency or other things. This is all like out of pocket, but we certainly do have that information on our speakingwomenshealthcom website and I have had a few patients who have wanted to have that testing done. I wondered if you had any opinion about it.
Speaker 2:I would say that it's not ready for clinical prime time. Whatever insights we're getting, they're probably very noisy, they're potentially misleading.
Speaker 2:I would say at this time Unless you're one of the few people that fall into really rare situations. For instance, there are like hereditary obesity syndromes, essentially. So if you're someone with a hereditary obesity syndrome, those need to be handled by specialist teams and that's obviously not a situation where you can be typically managed in the way anyone else could be. And there's there's a lot to learn out there. I'm not saying that this can't have a future, um, and it may, just it may not necessarily be related to what you should eat. Some of it may be like we, we may learn that some people. It may not be related all to weight either, for instance. So I know you're interested in, you're very on me to make sure I was tested to be, if I was a cystic fibrosis carrier or not right.
Speaker 2:So the most common cystic fibrosis variant in the population. It's this small deletion of a single amino acid in the CFTR which is the gene for cystic fibrosis. And that gene it's the most common one and apparently there's potentially some heterozygote advantage associated with being a carrier.
Speaker 1:Interesting.
Speaker 2:As in, you have a lower rate of irritable bowel syndrome. You're much less likely to have irritable bowel syndrome if you are a carrier for the cystic fibrosis mutation.
Speaker 1:Interesting, but you didn't need to be tested because your wife, who was pregnant, tested. So if she's not a carrier, then they don't usually check the males.
Speaker 2:Right. So actually I wasn't tested, but we tested her and because she wasn't a carrier, it didn't matter for me, but we obviously pursued the testing at your, at your urging.
Speaker 1:Uh-huh and oh, I didn't. I didn't know what were the results.
Speaker 2:Oh she's. I didn't get the test is what I'm saying because she was not good. You didn't need the test because she was negative.
Speaker 1:That's what I thought.
Speaker 2:Yeah, yeah, yeah, but I would have if she was yeah.
Speaker 1:Of course, of course. It's interesting that people are getting so much genetic testing done and we have columns on recreational genetic testing and that is not adequate for cancer genetic testing and I have so many patients, including, you know, highly educated people, who say, oh no, I don't have BRCA, I already had 23 and me.
Speaker 2:Yeah, yes, those over those commercial kits, the ancestry kits, those are what we call sparse. So they're. They're not looking at the whole sequence of a gene in any case, they're looking at these small changes at single locations and those are called single nucleotide polymorphisms, or SNPs for short. Yeah, so it's very sparse. You're not getting whole genome information, and it's now very cheap to get whole genome information. But you should of course pursue that in a professional setting. Get real clinical testing done, if there's a reason to be getting that testing done.
Speaker 1:Yes, and the associated counseling. In fact, in season three I have a genetic counselor, ryan Noss, who will be on talking about the GINA law and just a lot of the implications you know for genetic testing. It's not just something you go and have done. It really needs to be done very thoughtfully and carefully and with informed consent and a lot of information. And you are listening to the Speaking of Women's Health podcast. I'm your host, dr Holly Thacker, interviewing Dr Stetson Thacker, a genomics expert and prolific reader and writer, and we're talking about anti-aging. Is there any anti-aging supplements that you think really work or that you would consider people thinking about or talking to their clinicians about?
Speaker 2:So I want to draw a distinction here between, again, lifespan, which is how long somebody's going to live, and then their health span, which is essentially how long they live at good health.
Speaker 1:Exactly, that's a very important point. You can live a long time and suffer and be decrepit and have dementia and lots of problems.
Speaker 2:Yes, yes, exactly. So I wouldn't say there's anything pharmaceutical wise or supplement wise that you can take and you can definitively extend your life in some way. Now there's a lot of excitement around drugs like metformin or rapamycin and there's some theoretical reasons or some animal evidence that would suggest that maybe those can have some longevity benefits in terms of actually extending your lifespan, but in terms of the human data available to demonstrate that it's essentially non-existent a little bit better in that form. And then the rapamycin. But there's there's really nothing that I could point to and say with confidence of any kind that you can take and that you'll live longer in any way. I remember when you were starting your PhD.
Speaker 1:you came home one day and said hey, I think I should start on metformin. I'm like what are you talking about? Your blood sugar is fine, you're very healthy and you have a low body fat index and normal blood sugar.
Speaker 2:So what was it that impressed you so much about metformin glucavage? I think I was just looking too much or reading too much into, say, animal and pre-clinical data, and I think a lot of times we get, as scientists, sometimes overconfident about how much those positive findings will extrapolate to humans yeah, that's a very important point we do a lot of research in mice and mouse models, but not and mice, despite being mammals, okay.
Speaker 2:So they're at least in related to humans. In that way, they're still very different, you know they. Their average lifespan is like two to three years. They're nocturnal, you know, they're very, it's a very different species.
Speaker 2:Not everything is going to translate in addition to that, the types of mice that we study in science are very different than even like a wild mouse. They're extremely, extremely inbred In most cases. It causes a lot of weirdness and all this, for instance, we probably would touch on the topic of caloric restriction. There is a lot of animal evidence that would say that caloric restriction extends lifespans, and it does in these weird mouse models. But when you look at across outbred mouse models that effect kind of goes away.
Speaker 2:So it's a little bit of an artifact of looking at these really weird situations where the mice, being so inbred, has artificially shortened their lifespan versus like a wild mouse has artificially shortened their lifespan versus like a wild mouse, and then when they reduce the calories intake, in this situation there's a little bit of a benefit to lifespan, but that doesn't necessarily then generalize everything. Oh, if you were a human and you just eat less food, you're going to live longer, and we can't really say that. So it's important to remember whatever you read as a scientific study, it may not jump all the way up to humans, so it's important to realize that. To be very confident in it, we need to see it studied in humans and replicated and have the study design done in a way that allows us to confidently show that there's a causal relationship between the variable that we're changing and the effect that we're measuring. It's just important to remember those things.
Speaker 1:Clinically. I advise a lot of my patients who are not pregnant, who are fully grown, who are trying to deal with preventing weight gain or getting weight down, which is like one of the most perennial problems of midlife women, to consider intermittent fasting, because it does drop insulin levels and a lot of times it makes it easier for people to stick to a diet and not just mindlessly snack. Do you have any comments about rapamycin and why this became like such a thing and why there's people who are not organ transplants that are going and seeing doctors and taking this?
Speaker 2:why there's people who are not organ transplants that are going and seeing doctors and taking this. Yeah, it's a little crazy. It's rapamycin, it's a potent immunosuppressive, right? Yes, some of these people that take this for longevity which these people fall into like this biohacker category, where they're sort of rogues practicing science on themselves they're sort of rogues practicing science on themselves, and I mean, in some respects, it's good to have people try things and find things out, but it's not something we can recommend to people broadly at all.
Speaker 2:They're taking a lot of risk onto themselves. But so rapamycin, it inhibits this protein called mTOR, which is defined by the fact that it's a target of rapamycin. It's the mammalian target of rapamycin. And so mTOR as a protein, it kind of sits at the center of the metabolic function of cells and it's a signaling molecule but it's coordinating the metabolic activity of the cell. Is the cell going to grow? Is it going to participate in, basically, anabolic behavior? Is it going to participate in catabolic behavior? Mtor just focuses on anabolics of the building behavior.
Speaker 2:There's another protein, ampk, which focuses on the catabolic, or the breaking things down behavior. And so the idea is, if you do a little bit more breaking down, recycle things, recycling things, you're going to rejuvenate essentially the cellular tissue. You're going to be able to resist the processes of aging. Obviously there's some theories of aging that relate to essentially protein turnover or how much essentially related to how much catabolism, how much of this recycling is going on in the cell. So that's what they think they're promoting with this rapamycin. Obviously, when you're putting something in your body and it's systemic and like there's all these effects, for instance, like it's an immunosuppressant, like you're affecting all these different tissues. So tissues are doing different things. There's a tenuous balance, there's homeostasis. It's not simply something we can just intervene on by something you put into your body through your mouth.
Speaker 1:Yeah, and there can also be a lot of off-target effects and I think, sadly, people try to look for some simple pill they can swallow instead of going to bed on time, getting their exercise, really trying to eat whole foods and do a lot of the basic things which are not always all that exciting and do a lot of the basic things which are not always all that exciting. It seems like there's just so much out there about these popular anti-aging hacks, walking barefoot outside seeing the sunlight, which I think it's good for circadian rhythm. I think there is probably something to it. We have too much screen time and we don't always have the right lights. There's a big craze about red light. I've got a column we just posted on red light therapy and these subversions of extreme heat, extreme cold. Your younger brother, my youngest son, grayson's always telling me get a sauna, mom, go, sit there and it'll be like a workout without you having to work out.
Speaker 2:Yeah, I would say to these things that if something subjectively makes you feel good and there aren't many risks associated with it, then you should do it, and if you feel like it's providing a functional benefit, then I think for the most part, it's okay. Now, especially with things like where you're not actually putting something inside of your body, when it's just you know using a sauna or exercising barefoot or going out in the sun. You know these are, these are minimal risks, sorts of things.
Speaker 1:Well, what about these cold plunges? Didn't you go do a cold plunge?
Speaker 2:Yes, I mean I think the idea is yeah, the idea is again like you're essentially like wrapping, ramping up stress responses. It's similar to exercise. I think it's basically you're simulating exercise in a lot of ways and modulating inflammation. You know, when you have an injury, what do we do with our injuries? A lot of times we're putting, we're putting ice on it.
Speaker 1:We're putting heat on it, right, so?
Speaker 2:these are this tried and true methods for essentially trying to modulate what is going on inflammation, wise in the body, just to rejuvenate tissue, and so, again, I think these are things that are contributing to how your body is functioning and that's why it probably makes people subjectively feel better. But is it exactly going to make your life longer? Probably not.
Speaker 1:Probably, not at all, probably not.
Speaker 2:There's some tension between making your body more functional or more fit and then living longer in a lot of ways, so we can get into that a little bit. For example, I think this touches on the difference between how long men and women live.
Speaker 1:Yes, yes, that is fascinating to me.
Speaker 2:Right. So this is really widely known. It's observed across essentially all societies I think it's universal and even in other animal species most mammals, I believe this is true for is that the male of the species lives a shorter life than the female of the species, and so there's some sort of trade-off that the males of a species are making that is costing them life years relative to the female sex, and there's different theories about this, of course, but I think it boils down to the sex chromosomes and testosterone. And the trade-off that is being made is men are essentially ramping up to be more reproductively fit at the cost of some robustness in the rest of their system, and some of this, of course, has a behavioral manifestation in humans. So, obviously, men are engaged young men especially are engaged in riskier behaviors that often shorten their lives.
Speaker 1:And jobs or war or other things that obviously put their physical bodies, which are generally stronger and bigger, in part because of testosterone, into harm's way a little more frequently.
Speaker 2:Yep, and some of the giveaway here is that you can do the demographic analysis and you can look at the mortality rates at different age groups. Group them by different ages. You look at men and women mortality rates in infancy. It's higher for men much higher for males. Yes, high for males at in youth, higher for males, of course yes in old age higher for males. Of course, that's just every group right.
Speaker 2:And so the question if you're living a normal life and you know you've already made it to middle age, you're, you're living, you're expected to live a full life. Well, why? Why does men still live a shorter life? Well, I think again, testosterone is, is still playing a role here. Obviously, men die of heart disease more often, for example, so there's some sort of relationship with that, the tissue there. And then I also think there's something that testosterone is doing with the immune system, making men a little bit less robust in that regard as well. And obviously androgens have been associated, steroid hormones in general associated with an immunosuppressive effect. So ramping up the testosterone to be strong and ready to engage, engage in aggressive, aggressive behaviors, to be reproductively fit, is coming at the cost of taking care of those other things in the body there's a trade-off, that happens.
Speaker 1:But you talked about the length of age versus the functional length of age and certainly if you walk into most nursing homes, you're going to see 80% female and only 20% male. So if you live longer but you're infirm which we see in a lot of women with muscle loss and memory loss and you know, not all of it but a significant portion of it does relate to hormone deficiency, which is, you know, why I focused my career on, you know, trying to improve people at midlife so that they can live the second half of their life more favorably and functionally. If you're not really getting extra functional years, it doesn't seem to be an advantage as a female.
Speaker 2:Yep, yep, yeah. So we don't have a great standardized way, necessarily, of measuring health span. There's some subjectivity to the measure. So what exactly does it account for? We haven't, we don't have a long history of measuring health span or a standardized way of doing it, whereas, like, we can easily see when someone's born and when someone dies.
Speaker 1:So it's that's the yeah, assuming the records are correct and people aren't trying to get their government check right, which nowadays is a little, at least in a place like in the US.
Speaker 2:for the most part, you can trust the data.
Speaker 1:Oh yeah, as soon as that death certificate goes in, the government goes and takes out a check if they've already deposited the check for that person's lifespan. I mean it's yeah, they know. They certainly know right away, that is for sure, man. So I always ask my patients a patients, a family history, you know, for those people that have it and are not adopted. And even if they're adopted, there's still a lot of open adoptions or ways that people contact their biological relatives. But, that being said, I always put a lot of uh credence in knowing their first degree relatives and what they died from. And certainly you do see these families where you know everybody's like living into their nineties and they're functioning and independent. So there must be some genetic selection for that.
Speaker 2:Well, I wouldn't say genetic selection, not selection, that's right.
Speaker 1:Genetic variation, you reproduce when you're younger, not older right. Yeah, genetic variation, that's right.
Speaker 2:Although, yeah, although there could be selection on something that then would also lead to longevity. I mean, it's not that living long is entirely, it's not that long lives are entirely not visible to the evolutionary process, but it's much less so, of course. But you're right in that genetics likely plays a very important part in extreme longevity, in that genetics likely plays a very important part in extreme longevity. So people who are making it over 100 years, so centenarians, super centenarians, which are the people who make it to 110 or beyond, so there's very few of these people. Now there's family studies, there's twin studies, there's genome-wide association studies, there's these localized studies of what certain genes do. For instance, there's this ApoE gene, which is a lipid carrier protein, and there's a certain variant of this gene, the E4 allele, which is strongly associated with Alzheimer's disease.
Speaker 1:Yes, yes, I have some patients who go and get that testing done.
Speaker 2:Yes, so it's associated with. If you're homozygous, meaning you have two of these from both parents, you are likely to get Alzheimer's much higher risk versus the general population and have a shorter life because of that, and so that's one example where genes can figure very strongly into longevity, and there is actually emerging evidence and I'll talk about this in future podcasts of the interaction of menopausal hormone therapy and the different ApoE subtypes, because it seems like some subtypes seem to have more of a positive effect in cognition with estrogen.
Speaker 2:Yeah, so I didn't mention it, but the E2 allele of ApoE is associated is a little bit more common, in centenarians, for example. I have to say it's again, any allele which is typically referring to a variant in a gene that is common in the population. So, like more than 1% of people will be a carrier of this variant of the gene. And so when you compare it across a population, you're saying, like you know, 75% of the people who live to 100 may have this, versus the 25% have it who didn't live to 100, for example. So like what?
Speaker 2:the actual contribution to the increase in lifespan may be quite small when you're looking at these small variations, but what we do know is that there, the way that long life may be conferred genetically, may just be having fewer deleterious mutations overall and so there was this recent study that was looking at a group of Ashkenazi Jewish people and they of them that have extremely long lives, and they were comparing them to a control group, and they were showing that those that have fewer deleterious mutations as in mutations that will essentially inactivate the gene mutations, as in mutations that will essentially inactivate the gene they're living longer lives.
Speaker 2:So this is one of the mechanisms essentially their their genome is is more robust in terms of it, they have more functionality across the genome that they're not carrying essentially deleterious alleles and they live longer because of this. And this figures nicely into. We haven't thought, we haven't talked about theories of aging like why do humans age, for example, and so one of the most popular theories of aging is called the somatic theory of aging, the somatic mutation theory of aging. And that's just over your lifespan, you're accumulating mutations in the DNA across the various cells of your body, and accumulating those mutations contributes to the aging process because the cell function is regulated very tightly by certain genetic programs, and so the more mutations that you accumulate in the cells, the more the genetic program of those cells is going to be dysregulated. It's the same idea of why people get cancer.
Speaker 1:And I think that's one of the reasons why there's been these proliferations of tests that people can order online which are very expensive and not really validated, looking at telomere size and aging and methylation. So I would assume that at this point in time it's not ready for prime time and you wouldn't recommend people waste their money.
Speaker 2:Yeah, those are not clinical grade, although there has been evidence that shows that the methylation pattern that some of those tests look at is tightly correlated to the number of somatic mutations that are being found in a cell. And so that would be if the somatic mutation theory of aging is correct, which I'm sure probably is correct and is certainly correct in some ways, but it may not be the total story.
Speaker 1:The total story. Yes, and we'll have to bring you back to go into this some more.
Speaker 2:Yes, so to the extent that it is true, it is capturing something. Those methylation tests probably do capture something, but again, there are different tissues in your body, so these tests probably just look at. The methylation tests probably do capture something, but again, there are different tissues in your body, so these tests probably just look at the methylation patterns in blood, which may be a good proxy generally. But again, these are all. It's never the complete story. It's not something that we should just wholly believe and, of course, if you've got a bad result on the test or a good result on the test, it doesn't mean you should just wholly change your behavior. Obviously, people should be focusing on living generally healthy lives from the wisdom that we've accumulated over time.
Speaker 1:Up to this day and we know what those things are. So, as we're wrapping this up, tell us about your new podcast that you just launched and how people can listen to you and all your intellectual insights and interesting perspectives.
Speaker 2:Yes, so I recently launched a sort of general interest, cultural commentary or special topics podcast with a friend of mine which I met through my wife. He's the husband of one of my wife's lifelong friends. Wife, he's the husband of one of my wife's lifelong friends. He was born in Kathmandu, nepal, and so we've called our podcast Views from Cleve Mandu, mashing up our two different hometowns. I'm from Cleveland, ohio, and so we recently started the podcast.
Speaker 1:We have four episodes, I believe, we published our fifth episode this week and yeah, so check it out at. Yeah, you'll probably have a lot wwwleavemyandoocom and I write at Substack as well. So we will put the podcast in the show notes and your Substack and by the time this airs in episode three, I imagine you'll have more than five podcasts by then. But that is great and so people can catch that.
Speaker 2:We're on spotify and anywhere you get available any, any any of the main pot uh podcast players.
Speaker 1:So definitely it's on apple and it's on spotify and it is called views from cleve mandu, and you write at substack dot com on. You have both a scientific substack and then a book review and cultural substacks, which are very interesting. Although I don't think you always appreciate your mother's comments, I would say that. So, although, like I always tell my fellows, I've been running this specialized women's health fellowship and, of course, publishing is a big part of the academic career and early on people don't like criticisms of people's writing and editing, but I do think it makes you a more robust writer and communicator. So I would say that.
Speaker 1:So thanks to our listeners for joining us today and don't miss another episode of our Speaking of Women's Health podcast, and you can subscribe for free anywhere where you listen on Apple Podcasts, itunes, spotify, check out our show notes. And thanks to our loyal listeners for tuning in. And if you want to help support the program, please give us a five-star rating and you can share it with others. It's free and you can also donate to speakingofwomenshealthcom, our nonprofit. So thanks again and we'll see you next time in the Sunflower House.
Speaker 2:Thanks for having me, Mom. Bye.
Speaker 1:Bye.
