FoundMyFitness - #046 Dr. Elissa Epel on Telomeres and the Role of Stress Biology in Cellular Aging

Episode Date: June 10, 2019

Elissa Epel Elissa Epel, PhD, is a Professor in the Department of Psychiatry at the University of California, San Francisco where she serves as the director of the Aging, Metabolism, and Emotions Center. Her research centers on the mechanisms of healthy aging and the associations between stress, telomere length, addiction, eating, and metabolic health. In this episode, we dive deep into the world of telomeres, the length of which is one of the useful biomarkers scientists have for getting a sense of the differences between how individuals or groups of individuals age. Telomere shortening is both a cause and a symptom of aging and plays key roles in not only how long we live, but in how well. Lifestyle factors such as poor nutrition and smoking can accelerate telomere shortening by generating oxidative stress and inflammation. In this episode, we discuss: (00:00) Introduction and overview (12:14) What are telomeres (17:23) Telomerase activity and cancer (22:22) Factors affecting telomere length: (24:50) Diet, coffee, and sugar (30:16) Chronic stress (35:01) Exercise (40:14) Pregnancy and pre-conception (51:19) Omega-3s EPA and DHA (52:12) Vitamin D (54:01) Weight loss and glucose management (01:00:30) Meditation (01:07:39) Consumer telomere length tests If you're interested in learning more, you can read the full show notes here. Join over 300,000 people and get the latest distilled information straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

Welcome back, friends, to a fresh episode of the Found My Fitness podcast, a little digital oasis where we can talk about the science of aging, health span, well-being, and more, usually through the lens of cellular and molecular biology. Today's episode features Dr. Alyssa Eppel, a professor in the Department of Psychiatry at the University of California, San Francisco, and many other roles, including director of the aging, metabolism, and emotion center at UCSF. Dr. Appel's research centers on the mechanisms of healthy aging and the associations between stress, addiction, eating, and metabolic health. But one of the reasons I was particularly excited to have Dr. Appel on the podcast relates to her deep expertise in the world of telomere science.

Telemere's are distinct structures comprised of short, repetitive sequences of DNA nucleotides present on the ends of our chromosomes. They form a protective cap to protect the chromosomes from damage. Telomere length is one of the useful biomarkers scientists have for getting a sense of the differences between how individuals or groups of individuals age. This is because telomeres get shorter every year as a function of cell division, playing a role in what is known as replicative senescence, a process that limits the number of cell divisions as cell can undergo, a limit that varies by cell type and factors like the expression of a special

telomere rebuilding enzyme called telomerase. But as you'll find out in this episode, telomere biology is complex. While it is no doubt important for us to keep healthy, telomeres and do what we can to maintain them, the shortening of telomeres may be a delicate balance that biology uses to try to protect us from other dangers, like cancer. Now for the teaser, in this episode, Dr. Appelan and I discuss the function of telomeres and a discussion about telomere length as a biomarker for aging versus its place as an actual regulator of aging. How a specialized enzyme

called telomerase has the ability to rebuild telomeres after they've been shortened by adding back base pairs. The enormous tenfold difference in telomerase enzyme expression between what is found in cancer cells, which is hijacking and overexpressing the enzyme as an immortalization strategy versus what is ordinarily in blood cells. How telomere diseases may impact offspring even without direct transmission of an affected genealil because of the unique transmissible quality of telomere length where it is heritable from parents via epigenetic means. A special concept Dr. Uppel refers to as the exposome, which makes up the totality of non-genetic exposures that may influence telomere length and health span and can include everything from food, stressors, education,

and financial status, chemical exposures, and more. Emerging science of air pollution, where some evidence suggests that small particle exposure may increase telomere attrition, the impact of diet on telomere length, and what some of the strongest factors are that seem to associate with either shorter or longer telomeres. The association of caffeinated coffee consumption with longer telomere length. The impact sugar-sweetened beverage consumption may disproportionately have on telomere length, where one study showed as much as 4.6 additional years of aging. The beneficial impact of aerobic exercise on telomere length as a reducer of stress and rheumative thinking. The impact of sex differences when it comes to lifespan

and some of the mechanisms that may be driving a part of that. The emerging science of how a mother's mental health or stress may impact the uterine environment and influence newborn telomere length. The special importance of preconception health, which may impact the aging program of offspring through the transmission of epigenetic signals conferred by the germline. Dr. Eppel's concern surrounding the potential cancer and aging trade-off of longer telomeres and the shadow that might be cast over supplements marketed to directly boost telomerase activity, which do not yet have a clinically proven profile of safety. How marine omega-3 fatty acids EPA and DHA may be one of the safest supplements to delayed telomere attrition,

and how one four-month double-blinded trial showed that omega-3 could even lengthen telomeres. The overall strength of exercise as a direct modifier of long-term telomere maintenance. How losing 10% of body weight and then keeping it off for over 12 months was shown to lengthen telomeres in obese participants. Dr. Eppel's tips on making sustainable lifestyle changes that have a quote-unquote stickiness and help us, to stay on the path to better aging. Some of the concerns surrounding the validity and accuracy of consumer-available telomere tests, as well as the difficulty in interpreting results from a single snapshot from individual versus a population, and so much more.

A few quick mentions before we get to the podcast. You can find a video version of this podcast with on-screen references, figures, definitions, along with an in-depth episode summary, a timeline breaking down what was said and when, a glossary and a full transcript for this podcast and all podcasts by checking out the episode page on my website at foundmyfitness.com forward slash episodes. That's found my fitness.com forward slash epi s o d es episodes. You can also check out the highlights for this episode on the found my fitness clips channel by heading over to found my fitness.com forward slash clips. all of these over-the-top, in-depth resources useful due to the sometimes technical nature of this podcast

are made possible by the financial support of an amazing group of people. I really couldn't make this happen without them. To join my crew of voluntary monthly supporters, head over to foundmyfitness.com forward slash crowd sponsor. Once again, that's foundmyfitness.com forward slash crowd sponsor, C-R-O-W-D-S-P-O-N-S-O-R. If you were interested in the genetics of telomere length, in other words, snips that are associated with either shorter or longer telomere length, and you have a consumer genetic data file from a service like 23 and me, I've made available a telomere report on the genetics page of my website. You can find that at foundmyfitness.com forward slash genetics. And since it's a basic report covering just those snips, you can run it for free.

Finally, one of the most important mentions. In 2017, Dr. Eppel co-authored a New York Times bestselling book called The Telemere Effect with Nobel Prize winner and frequent collaborator Dr. Elizabeth Blackburn. If you enjoy this conversation, I definitely recommend checking it out. That's the telomere effect. I'll give this a plug at the end of the show too as a little reminder. Now on to the podcast. Hello everyone. I'm sitting here with Dr. Alyssa Eppel, who is the director of the aging metabolism and emotion center and the professor of psychiatry at the University of California, San Francisco. her research focuses quite broadly on how various types of stress impact the aging process. So that's kind of a very broad term, the aging process.

Maybe you can shed some light on what that actually means. Yeah. So one way to look at aging is to see when people die. A little more fine-tune is to see when they get sick, when they get a real chronic disease diagnosed. And then the way that me and many aging researchers look at it is let's look underneath into the cells at the aging biology. And the aging biology is something that occurs processes throughout our whole life. So we're born with certain parameters set.

How long are our telomeres? How well-functioning our mitochondria? What's our epigenetic clock? So there's these mechanisms that we can measure and look at in the cell that are actually. throughout life that wear down with poor health and years of living. And it's the difference between how quickly they wear down versus chronological time. So aging biology is kind of elastic. So some people's aging biology process are robust and it doesn't wear out as much.

Whereas for other people, they age like in dog years, right? So like one year to someone might be seven years to another person with this terrible lifestyle and a lot of stress. Did you read that study that came out a couple of years ago? I think it was PNAS where like a whole host like maybe eight or 12 different biomarkers were looked at, some of the ones you just mentioned, telomere length and epigenetic signatures. And there was like such a huge variety.

Like the effects of how these different biomarkers looked at in people the same age were so different. Yes, Daniel Belski's work. Right. So this is a really big important trend in our field, which is to look at. at these algorithms or panels of these indices of aging. So not just focusing on one, but looking at them all together and seeing how that changes in young people over time. So that really is a really fruitful way for us to be looking at aging because we don't want to just wait until people get

disease. We know that aging is one of the main causes of all later diseases, except for the genetic diseases. So it sounds like you're also talking a lot about differences between someone's lifespan how long they live and their health span. Okay, so I'm glad you brought that up because it is a hugely important shift for us to, rather than focus on longevity and maximal longevity, to focus on years of healthy living, the health span. And so what's happening with longevity is it's increasing dramatically. It's beautiful, right?

So for men, life expectance is around 78 years in the United States. For women, it's around 83 years. And that is a dramatic shift from even 100 years ago. So we are doing great in terms of longevity overall, but we're doing terrible when you look at actual healthy years of living. Because the longer we, well, first of all, no one wants to live long with disease and suffering. It's all about healthy years anyway. That would be people who have, you know, taking care of older relatives know that. You don't want to live long when you're suffering.

So really, the longer we live, the more likely we are to get dementia and disability and need to, you know, live in institutions, et cetera. So that's the kind of double-edged sword of living long. So what we really want to focus on is how can we live well? with optimal slow aging for as long as we can, and then die pretty quickly before we're like suffering with dementia. Right. So delaying age-related disease, delaying cardiovascular disease, delaying neurodegenerative disease, as you mentioned, delaying cancer. Right. Like having all those things where you're basically improving the quality of life as opposed to just sort of, you know, increasing the how long you live, but just living kind of degenerative kind of lifestyle. And it's a whole

formula. So it's not one thing. The levers that control aging are the things that we know about, but we easily forget. So we often hear about the lifestyle thing. So activity, nutrition, stress. So those are really important to manage well, and they add up over time. So like a healthy lifestyle, not extreme, but just healthy, is in midlife predicts longer telomeres, predicts, longevity decades later. So we don't need to be extreme about this. We just need to really notice the toxic things we're doing and, you know, like smoking and sitting too much and not, you know, leaving stress unchecked and just having years and years of feeling vigilant and not getting enough sleep. And so there's a lot of low-hanging fruit that we know

about. And then there are some things that we don't know about, we don't pay as much attention to. And so some of those are things like positive stress, which we can talk more about later if you want, but doing things that actually activate our anti-aging system, short-term activating things, psychological or physiological. And then also like the web of social connections that we have, the more positive they are, the more we feel supported. Those are really important predictors of longevity, too. You mentioned telomeres a few times. So for people listening, or viewing that aren't quite familiar with telomere biology, maybe you can give a quick, just background on what telomeres are

and why they are involved in the aging process, whether biomarkers for aging. Sure. So people like to think of them as like the aglets at the tips of shoelaces, those plastic caps to keep shoelaces from fraying. So when you think of our linear chromosomes, they're all capped at the ends with this wound up strings of DNA, repeating DNA, called telomere.

And it's, they are protecting the genome from damage. So they're very important that way. They are sensing chemical signals of stress in the cell. And so if there becomes a toxic situation, they think the cell is in danger, they are going to, well, that cell can shut down to protect the body. But also the telomeres get worn down very quickly when there's a lot of stress. And so stress biology and aging biology are actually really tight. up intimately. They take the hit.

So they're trying to protect your DNA from potentially acquiring a mutation that could lead to something like cancer. Yes. So they sort of take the hit for the cell. Right. Right. In your experience, how much would you say that telomere length? So the telomeres get shorter with time and shorter telomeres are supposed to correspond

to aging? How much would you say that telomere length? regulates the aging process, like actually plays an active role versus just is a biomarker, something that's just biomarking the aging process. Yeah, that's a good question. So telomeres are one specific pathway of how a cell ages and how our tissue ages. And the pathway is this. It's called replicative senescence, and it's basically how long can that cell continue to divide

and divide and replenish into. new, fresh young cells. So the telomeres, when they get too short, prevent that particular cell, whether it's an immune cell or a neuron in our hippocampus or the lining of our cardiovascular system, we need those cells to replenish throughout the decades. When the telomere gets too short, that cell stops dividing. And so it's basically a little window into how long can these cells continue dividing. If the telomeres are long, they have a long potential for replenishing tissue. So it sounds like the telomeres are much more important in stem cell populations,

populations that are really responsible for replenishing variety of cell types of tissues. Right, absolutely. And so there's a, you know, would you say that there's a difference between how telomeres shorten or, you know, what the attrition rate of telomeres and stem cells are versus other cell types that are not stem cells? Yes, yes. So if we could measure stem cells more easily, we would realize that partly what we're measuring in any tissue is the health and longevity and telomelumina of the stem cell. So the stem cells lead to progenitor cells, and then there's all the offspring.

And so when we look at blood, we're looking at the offspring in the different circulating cells that roughly reflect the health of the stem cell. And there's a variety of different, so you're talking about the damage that happens with age and how that can accelerate telomere shortening because they sort of take the hit. They're protecting our DNA. There's an enzyme that can rebuild telomeres, right? Can you talk a little bit about that enzyme? But it's not active in every cell. Right.

So the telomerase enzyme is a very interesting enzyme that is interesting. cellular that is, has the ability to actually rebuild telomeres by adding back base pairs. So it's a RNA reverse transcriptase. And this was discovered by Liz Blackburn and Carol Greider and colleagues made, you know, over 25 years ago. And they were showing how if you knock it down, the cells cannot divide anymore. And if you upregulated, the cells become immortal. So it is an important regulator of how long a cell can divide. It's determining, it's one of the major determinants of telomere length, because if your telomere's shortened and you have a lot of telomeres, you can repair them, you maybe even can lengthen them. And telomerase, if I remember correctly,

it's more active in stem cells than in somatic cells for the most part. Yeah. So at UCSF, my colleague, Julin, actually has an assay that's very sensitive and can measure the level of telomeres in our normal blood cells. They're not cancerous. They're not stem cells, but you can still measure the level. And that is associated with health, with metabolic health, with social economic circumstances. So interesting. So you mentioned this sort of potentially double-edgedged sword with in terms of, you know, the telomeres getting critically short and telomeres activity going down and that leading to cellular senescence. We've had Dr. Judy Campesia on the podcast. We've talked a lot about since, or even apoptosis, or you said they can become immortal when telomerase becomes

overactive. And basically, it's just constantly rebuilding the telomeres. And immortality in some cases with the overactive telomeres associated with certain types of cancer. So what would you say, like, you know, measuring, you're just talking about measuring telomeres activity in white blood cells, and that's sort of a marker for, you know, the aging probably how well a person's aging or how well the cells are aging. Is that, is there something like, is there like a threshold for when it becomes too active and it's like a cancer cell? Like, can you detect that the difference? Like is it when it's like always active? Well, so in our research,

we always make, we're not measuring any cancer cells. Otherwise, I mean, they're tenfold higher in telomerase, so it would mess up our measures. Yeah. So it becomes in cancer cells, it's kind of what I was asking. Like what degree is? It becomes like out of the physiological normal range. Okay. Yeah. So it is true that when you, that tumors develop a mechanism so that the telomerase is so high and they kind of immortalize themselves in that way. So the telomeres can be really short and maybe that's how there was a mutation in the first place,

but the telomerase is very protective. So it gets very high. Yeah. So, you know, this is a telomereic aging is complex. It's not just longer is better. In general, longer is better. and long telomeres genetically or measured in the blood predict less heart disease, less metabolic disease.

But actually longer telomeres, especially when you measure the genetic index, but sometimes also when you measure it in the blood, long telomers also predict greater risk of certain cancers like glioma and melanoma and several others. So it is, you know, it's homeostasis, it's physiology. you want to be long, but not extremely long, if you want to kind of have the best ratio of low risk for degenerative diseases, like dementia, heart disease, and low risk for cancer. It's definitely the complexities of telomer length always sort of fascinated me,

particularly because rodents, which don't have a very long lifespan, their telomeres are so long. Yes, right, right, right. And I never quite understood that. You know, it's like, what's going on there. There's just not a great model for humans. Because they don't die of short telomeres, unless you're like genetically manipulating them. Exactly. And there are some human diseases where telomeres are shortened.

And that does have a progeria type of effect, correct? Like more than that. Right. So that's super interesting. So in these certain handful of genetic disorders where people might have half the dose for telomerase, so their telomeres shorten quickly, they develop diseases that are, you can, you know, diseases of, of, bone marrow, they don't have enough white blood cells or these, you know, lung diseases. And so what is interesting about that is we know in those cases that it's the telomerase

and the short telomeres that are causing this early aging. And they can, they can transmit the, you know, the mutated gene to offspring and they get the aging syndrome. But they also can transmit just the short telomeres epigenetically, like in a direct epigenetic way. Oh, that's interesting. So the offspring may, thank goodness, not get the mutated gene, but they still get short telomeres. And they might have a mild aging syndrome from that. So that's something new that we know from these genetic disorders that might happen in us, too. We might be epigenetically transmitting short telomeres directly to our offspring,

whether we have a gene for that or not, just based on what our telomeres are. So let's talk about the environmental things that are regulating telomeres. So we just talked about genetics, things, you know, various environmental stressors, good or bad. One last point about genetics. So you earlier asked, like, is this a mark of aging or is it a mechanism? So it is probably both. And the way we know that it's the mechanism as well is, I mean, partly the example of some of these genetic disorders. But even more so, now we know that if you have a genetic propensity for long telomeres,

it directly predicts less heart disease and dementia. So those kind of Mendelian randomization studies are one of the best ways that we can say there's a direct physiological connection here. Right, yeah. I didn't know there was any Mendelian randomization studies on that. That's very interesting. So cardiovascular disease and dementia are two ones,

health outcomes that seem to be affected. Right. And then, as I said, the higher cancer risk for some of these. So different types of environmental things that can affect aging that a lot of focus of your research has to do with various types of stress. Whether it's diet-related or psychologically-related in stress. Right. So one way to think about all of those environmental things is to think about the ex-posome, all the factors that affect us that are outside of our skin. And so that includes a poor,

I'm just going to list factors that are part of our ex-posome, a poor neighborhood that's dangerous, poor diet, junk food or processed food diet, being exposed to a lot of psychological stress at work or domestic violence. So these types of things that are outside of us are also related to shorter telmers, all of the ones I just mentioned. And now there's a growing literature on chemical exposure. So this is very, very disturbing because we're all exposed to these chemicals like BP. and Roundup, and a lot of these chemicals in plastics, et cetera, are mimicking estrogen. They're linked to greater risk sometimes of cancer or other diseases like diabetes, metabolic

disease. And we can see, when we look at these aging biomarkers, we can see they're impacting them, inflammation and telomere shortening. So heavy metals, cadmium lead, those are directly in a dose response way related to our telomere shortness. Yeah, I think I actually read a skimmed, recent publication of yours with the academia. Yes, the metals. Yeah. I mean, we're supposed to chocolate and rice. I mean, that stuff is definitely. Oh, yeah, the arsenic, right. So it's alarming

that we are exposed to so many chemicals and even small particles in our air, air pollution. And all of these are impacting our aging biology in ways we don't know. So telomeres are an easy marker that we can measure and index. What is the effect of these chemical exposures? and the National Institute of Environmental Health has become very interested in using telomeres as an index of exposures. So, you know, in terms of your question of what in our environment is affecting us

more than we know, but so far, we've determined that things that lead to psychological stress, like an unsafe neighborhood, of course, traumatic experiences leave an imprint on telomeres, particularly when they're in youth, early in life. and then the the nutrition data is

I would say really not surprising and pretty consistent which is whole foods, healthy diet are related to longer telomeres and then you have the kind of foods that create this oxidative stress, inflammatory millia

and those are related to shorter telomeres. So what do I mean by like the pro-inflammatory foods? So red meat, particularly processed meat, sugar drinks, particularly sugared soda, high sugar foods. So those are pretty much the culprits that stand out. Mostly we understand about food patterns, but there are some foods that pop out. Caffeine is, sorry, caffeinated coffee is associated with longer telomeres. Yeah.

And it was quite a bit of coffee, right? Yeah, we just enjoyed a big. Yeah. Lots of it. Back to the sugar sweetened beverages, you mentioned that, because I did read that study, that, your study that was on the sugar-sweetened beverages and how that was associated with accelerated telomere shortening by something like close to five years or something, I think, if I remember correctly, it was something like that, where people, people that were drinking,

you know, a lot of these sodas and sugar-sweetened beverages had their biological age, as marked by a telomere length, looked older than their actual chronological age. Yeah. And so that was quite disturbing. Right. So that's, you know, that sugared beverage finding has been replicated many times by now. And it's not surprising because liquid sugar has more of an effect than sugar and food. It does cause, you know, a big metabolic disturbance immediately. And so if you're drinking that every day, you're, you should expect to have across the spectrum of aging biomarkers to have them be accelerated. And so it is, you know, it's coming out to be one of the biggest predictors of obesity and diabetes, which I'm talking about processed sugar, not just calories, particularly liquid sugar.

So, you know, we can all do our best to not have it. But what's even more powerful is when we get rid of it in our environment. So we just completed a study at our university where we just, the university banned all sugar beverages. It's because, I mean, it's just so ridiculous. That's awesome. Yeah, it's awesome. It's amazing. Go UCSF.

Yeah. And it's, I mean, it's so ironic that you go into, you know, many hospital cafeterias, and that's the drink that they're selling. And, you know, and so bottom line is that it reduced drinking dramatically and it reduced waste size, just getting rid of it at work. People can still have it at home. They can still bring it to work. So that's, those are the kinds of things we have to think about, like, you know, your child's eventual school

and these environments that you want to keep. children who are still developing habits surrounded by the healthy choices. Right. I remember reading, and this was an animal study, where these sugar-sweetened beverages activated dopamine pathways and, like, reward pathways in the brain. Similar to, like, some very bad recreational drugs. I mean, not to the same, it wasn't as robust, but like methamphetamine. I mean, these things, and, I mean, that is definitely, I would say, pretty scary that

there's an addictive aspect to the sugar as well. Well, I mean, I think that cannot be understated about why that is an epidemic that we cannot control yet. So in health span, we're doing okay preventing people from dying from diseases, right? Because we have medications and diagnostics. And so heart disease, stroke, like people are dying less from those. We're doing so well at keeping people alive and reducing those diseases. But at the same time, while those incidents and deaths are going down, the obesity incidence is going up. We cannot control it.

We don't have a medication for it, and it's addictive. And I think you just brought up a really good point. I mean, if medication's doing one thing where it's sort of like maybe extending a couple of years of your life because you're not going to have a heart attack or stroke as soon. But you're not fixing the problem, the cause of the problem, which could be your unhealthy diet or a variety of other types of psychological stress. or a combination of them, lack of sleep. So it is really important to address, you know, the problem, what's causing you to, you know, be at a high risk for type 2 diabetes or cardiovascular disease or stroke and address that problem because where a medication may help give you a couple

more years, the quality isn't going to be improved if you don't fix it. That's right. And quality is what matters. And then if you're having a toxic lifestyle, if you're sedentary and you're eating a junk food diet, that medication is not going to outweigh those big lifestyle effects. So like, let's take metformin. Lots of people take metformin for anti-aging. It's one of the very few pills that we have in sight that is probably slowing aging in some ways. But if you're taking metformin and you're still eating a lot of sugar, like many people with diabetes are doing because they have, you know,

their brain is wired that way right now with a hedonic addiction. That metformin is doing very very, very little. And so it's just an example of like, you know, let's work on these drugs. We absolutely need some breakthroughs to slow aging, but we cannot do it in this context of a toxic lifestyle. And you've actually done a lot, quite a bit of research on various types of interventions that do at least appear to slow aging. You've looked at associate studies, but you've also done some intervention trials as well. So getting to the psychological stress part, you have looked a lot at various types of psychological stressors, and those seem to be, as you mentioned, biomarked by a shorter telomer.

But you've also looked at a variety of other types of stress, which seems to be positive, more healthy, and that seems to sort of buffer some of those negative effects to some degree. Maybe we'll talk a little bit about that. So just to be really simplistic, when we think about stress, I know it has a bad rap, but that's because it's toxic stress that is causing dysregulated health and depression. And that means something really big, not necessarily what we're all suffering from, that neurotic feeling of stress and time pressure, but rather being, having traumatic things happen to you, particularly as a child, sets you up to feel threat responses much more in your brain and your body. So there's that kind of programming that happens in childhood. And then there's like the chronic stresses that we have as adults, which are things like

caregiving or job stress or domestic violence and relationships. So things that go on for years and years. So those are the types of things when we do see telomers shortening and inflammation. And the other, all the rest, like work stress is not related to telomere shortness. Oh really? Burnout is when you're really, you know, it's gone on long enough that you've gotten this kind of profile of demoralization from it. But not the typical adrenaline type stress that we deal with a lot. I mean, it's not good for us, but I'm just saying that's not going to show up as much or more

inconsistently. What about rumination when you're like constantly thinking about something that's negative? So I would say that rumination is part of chronic stress. That is when we, things happen and we carry it with us moment to moment day to day, we keep ourselves in a stress day. that's one of our targets in our interventions. We really like to look at rumination. That's why meditation is so interesting because it really targets, you can't be, you know, you can't be present and be ruminating at the same time. So you think that, because I, you know, oftentimes, you know, with something high stress, if I'm working on a project, definitely work related, I do tend to ruminate. Yeah. But I don't, I mean, it's not like I'm ruminating on it for a year. So that you

think there's a difference between that sort of short-term rumination where you're distracted by whatever projects you have to go and you're not present as much. Yeah. Versus like a very traumatic type of stress that's like, you know, financial stress or something. I think that the, it's easy for us to study the big events and the chronic events to see that showing up in our data on accelerated aging. What you're talking about is much harder to measure and study, but I absolutely do think it matters.

And we are looking at daily stress in our current. studies and seeing that people who have this profile of more elevated, we call it perseverative cognition or persevered thought processes, they have accelerated biomarkers of aging, telomere length, and inflammation. What is that? What is that? So you wake up and you're already worrying about the day, feeling like you can't control it, feeling anxious.

So there's a wake-up response because what is waking up? It should be clean slate, but it's not because we have these. different tendencies to maybe jump ahead already in the future, right? So worrying, planning, anticipating. We find that our caregivers do that a lot more. They wake up. They are already in a stress state. Their cortisol is higher.

That's what I was going to ask. Are there any other type of markers? Right. And if they're, whereas some caregivers wake up and they feel positive, they're looking forward to the day, they feel joy. They look better in their telomere enzyme and their cortisol. So waking up states are really important to notice. So like a pessimistic view versus optimistic view?

Is that kind of... So that's absolutely related. And that's kind of the bigger, you know, personality thing you take with you and you see the world in that way. So if you're high in pessimism, you just expect bad things to happen. Pessimism is related to shorter teal mirrors. We have that scale on our website because I think it's so important for people to, like, know their style.

You can't necessarily change your style. But if you know it, you can be aware of it. You can laugh at it. It's just going to diffuse its power more. Like, oh, that's, you know, that's my peasant. pessimistic thought. That's how I work. I actually find that a good workout, a very good, like, you know, if I do a really hard, intense run or sprint or a, you know, high-intensity bicycling spin class or something, that if I'm anxious or I have a, you know, like a sort of a pessimistic view of

something, absolutely helps alleviate that. Yes, absolutely. Your end of one has also been shown up in, you know, studies of exercise and studies by Eli Putterman showing that exercise actually does reduce ruminative processes. So Rhonda, can I ask you something? You are such a broad expert on aging. You've interviewed, you know, so many of the experts in the world on this. How much does sex differences come up? And I asked partly because we're at a meeting here on women's health. And I've just, you know, recently been scouring the human literature for trying to understand hormones and aging, sex hormones. And what have you learned? It almost never comes up.

And it's certainly a question that has remained unanswered in my mind for several years. And over the years, I've heard a variety of hypotheses, you know, ranging from immune system differences to different differential effects of testosterone on a variety of different tissues, particularly the immune system. But I don't, it really, you know, you started out this podcast. You mentioned the average lifespan in the United States for men was about 78 something and women was about 83, I think he said. So, and I did want to stop and ask you right there, why? Yeah, yeah. Why is that? Yeah.

So I've recently tried to read everything I could about this to understand it. And so this sex gap in longevity is robust across. cultures across countries. I mean, this is a fundamental thing about human biology. Species. Women live longer. Why? You know, there's the kind of obvious of like, well, there's two X chromosomes, so there's something protective about that backup copies. There's estrogen, which is protective in certain ways to the heart. And then there's like, kind of like psychology behavior, sex differences where men are more risky. They do more alcohol and abuse and risky things that lead to death.

So there's some of that. But that's just like tip of the iceberg. Like the truth is we don't really understand those differences. So here's what we know. Women have many cases when we look at the cells of women and men where their aging biology is more robust and slower. Example, women have much longer telomeres, like 100. of base pairs longer.

And that starts at birth. And that's probably related to sex hormones. So twins where there's a female and a male don't have different telomere lengths. So there's probably a masculization in the womb. So bottom line is this. Estrogen, when we look at these experimental models and in vitro and mice, estrogen is protective and anti-aging in a sense in that it upregulates telomerase. It improves mitochondrial health.

Those energy stores in our cells, those batteries are more robust. They create more ATP. They leak less oxidative stress. So if you, like, cause menopause in a rat, you're going to create more mitochondrial dysregulation in the brain and cognitive problems. And then if you replace estrogen, you fix it. So all this beautiful model suggesting estrogen is super anti-aging. but the idea of like, okay, do we have a new drug and it's estrogen and we're all going to live longer?

Absolutely not. The complexity of hormones in general, the different types, the different receptors, hormone therapy. It's appalling how little we know about aging and hormones in humans. Yeah. Are there any people that are really specializing in that field that you know about? So there are some people with very, you know, important programs of research. They're mostly not in humans. In humans, we know this.

We know that if you have a longer reproductive lifespan, meaning your menopause is a lot later, you're likely to have longer telomeres. If you give birth later, like in your 30s instead of your 20s, I mean, sorry, your last birth, you have longer telomeres. Those are also related to longevity, too, having the longer reproductive lifespan. So there are clues like, this is really important.

We should understand these sex differences. They're big. They're obviously related to hormones. hormones, but we really don't actually don't know how to act on them. We don't know, you know. I didn't know that the differences in Tethermore length between men and women were present at birth or male and female. Yeah, so I mean, this literature is just changing so rapidly. So people have discovered that and it's become somewhat of a consistent finding in recent years. Of course, there's differences with ethnicity and race. We also know that Tilemer length at birth

is impacted by the mom's health, her mental health, her nutrition. or physical health. So that's another whole world of, like, fabulous, important knowledge for us to act on. Is that something? So if you have a female who has, let's say, a poor diet, she drinks these sugar, sweetened beverages, for example, or a mother who's got some sort of chronic stress that she's under for whatever reason, maybe she's a caregiver or a parent with Alzheimer's disease. And so either of these cases, you know, before she gets pregnant, she's exposed to these types

of bad stress. Yeah, yeah, yeah. Now, let's say during pregnancy, she cuts out the sugar-sweetened beverages, you know, does that impact the telomeres of the offspring, or is there something that goes on during pregnancy? So I love these questions, and we absolutely should know the answers, because what happens during pregnancy and how the aging clocks are set, the epigenetic clock, the telomereng, the immune system, how much it's prime for inflammation, those are so important at

those are trajectories that have set up that baby for the rest of their life. These are lasting imprints. So we don't know. I'll tell you what we do know. So we do know that stress during pregnancy is associated with the shorter telomeres at birth in the cord blood. So that one has become... What kind of stress during pregnancy?

So that one has been measured in a couple different ways. So I think the life events are the kind of easiest thing to measure rather than the feelings of stress. So bad things that happen, job loss, more. victimization, financial events. So when you add those up during pregnancy, they predict shorter telomeres, but also it's been studied in the year before birth, and that predicts shorter telomeres in cord blood.

So here's what I think. I think your point about is it before pregnancy and the health that they came into pregnancy with? I think that is so much of what's happening for women and men. So it is the health of sperm and the health of eggs in pre-pregnancy, that is partly shaping the health through epigenetics. And so now that we know that there's, you know,

important epigenetics that dad is passing on too, we've got to pay attention to the health of the mom and the dad before they conceive. I mean, of course, throughout their life. But I think the health of sperm and eggs are critical before you get pregnant. And it's a really important point that most people of reproductive age do not think about.

particularly those that have unhealthy lifestyles because, you know, it's one thing to kind of sort of give up on your own. You're like, well, whatever, I'm, you know, it's my life. But when you start to think about your unborn child, I think people become a little more motivated. So you, with your immense knowledge of aging, what did you change when you got pregnant? Did you and your husband do anything differently? We've been really focused on good nutrition and good lifestyle for quite a lot. some time. But, you know, we certainly were very, you know, focused on making sure we're getting

lots of micronutrients, getting enough protein, getting omega-3 fatty acids. I mean, that was a big one. Exercise and definitely the stress, keeping the stress low, you know, and a lot of times for me, exercise helps with that. But just getting back quickly to the epigenetics, I know so much of this has been done in animals because it's just almost impossible to do a lot of studies in humans, but there was a study published a couple of years ago. I don't know if you read it. I don't remember. It was one of the top journals, like science or nature, maybe cell.

But what was looked at was sperm DNA in men that were obese and men that were non-obes, so healthy men. And there was a variety, like over 500 genes were changed in terms of like how their expression were, right? So their epigenetics were changed. And a lot of these genes had to be changed. to do with metabolism. They had to do with cognitive function. Men, these men underwent bariatric surgery. So these were obese, morbidly obese men. They underwent bariatric surgery,

and their sperm DNA was measured pretty close after, and then like a year later. And the epigenetics switched back to closer to what the, you know, lean men looked like. So it was really a very interesting kind of pilot study indicating there definitely seems to be a causal, like, you know, obesity is changing the, you know, a lot of, you know, the way these genes are in sperm DNA, you know, which is what you're passing on. Oh, my God. And there's been tons of studies showing, you know, male mice that are obese, have, you know, offspring, like, you know, female offspring that are, you know, get typed up one diabetes

because they get, like, some autoimmune thing. You know, so there's been lots of animal studies. Of course, you can want to translate so much of that. So I felt like that human study was really, you know, a good pilot study that really kind of show, look, this is happening in humans. And certainly make people think men aren't off the hook either. Yeah. You know, and that's oftentimes they're, you know, I think that I'm not sure a lot of men are aware of the fact that their lifestyle actually does matter.

Right. They're becoming more important than we think. Right. And the telomere length in the sperm DNA or in the sperm cells, that also plays a role in offspring as well. Do we know that, at least from animal studies? Yeah, it's a good question. It's paradoxical, but it turns out the longer, sperm are unlike the other types of cells where the longer they are around and replicate, the shorter the telomere's sperm opposite.

So older fathers have sperm with longer telomeres, and there is an effect in the offspring. So when we do studies, when we have the data to know, how old was your father when you were born? That's a covariate. That's something that shapes telomere length of the offspring. And what's the effect in the offspring? Is it shorter or longer? Yeah.

So longer. So sperm is telomere length is longer, and that can affect the offspring telomere length to be longer. Are there studies that have looked at whether or not having a longer telomere length to start predicts healthy aging? Okay, so that is, I believe, and I think many of us in this field believe that that is probably one of the biggest stories out there, which is telomere length at birth, that initial setting, which we know is partly genetic, but part of, prenatal environment and, you know, health of mom and dad and their sperm, their germline, you know, epigenetics. So that is one of the biggest determinants of their tumor length in late life. We all, you know, we can change it a little bit, but, you know, what you start with is a big factor. So no one has followed people to say, like, is it true that what you're

born with then predicts, you know, how soon you get sick and when you die? We don't know, but we think it probably is pretty big. So are you guys going to look at that? Yeah, yeah. Someone should. Yes, absolutely. And not just lifespan, but like you said, you know, look, does it predict cardiovascular disease? Well, let me tell you how important it is.

National Institute of Aging, which mostly studies old people. They have started to fund, they started to say, okay, midlife determines older health, so now they fund studies of midlife. And they've even funded us and our colleagues to look at pregnancy now, to see telomerell how it's transmitted and affected at birth from social and economic health, social economic disparities raise sex, sex, stress, how all of those shaped human life at birth because they believe it is going to create a healthy trajectory of aging or not. And so that's where they're investing now. It's kind of like having runway, right? You want to have something to start with.

Yeah. But you also just, I just thought of an important factor with a lot of nutrition stuff. studies that are looking at telomere length and how various types of nutrition or even, I would say, other lifestyle factors like sleep affect telomere length. It sounds like because there's such a really big effect of the psychological stress on telomere biology that socioeconomic status and educational background, all that stuff seems to be a huge confounding factor for those other studies, right? I mean, that's something that really needs to be accounted for. because you can have people that have poor nutrition, but that's because they're, you know,

maybe they have a lower socioeconomic background. And it is a factor. Education in particular. And so they're also stressed. You know, so it seems like, yeah, education. So it seems like certainly something that really should be considered big time. Yes. So it is, it has to be a covariate.

And age, chronological age has to be a covariate. You can't quite make sense of the data. Yeah, the education, the SES effect is interesting. It's there, inconsistently, small effect. What shows up the most is education. And I think that we even found... So the more educated, the longer the telomeres? Yes, exactly.

Positive correlation. My colleague, Janet Wojiki, found that in a low-income sample of Hispanic women, they're all pregnant, those who graduated high school had babies with longer telomeres in their cord blood. Those who did not graduate high school had babies with shorter. till we couldn't figure out anything that could explain it. We co-varied, you know, everything we could and they're all low income. So the education is probably filtering in so many different ways of promoting better health. You're making me feel good about my PhD. But so to this sort of transitioning to the next sort of topic is what you can do in your life to not only delay telomere

shortening, but maybe even reverse it. For example, things that can activate that enzyme, we talked about earlier, telomerase, which is important for, as you said, putting nucleotides back on telomeres. So things, I mean, people ultimately that are concerned about the aging process and about living healthier and increasing their health span and wanting to, you know, basically hold on to their telomeres. Yeah. You know, what sort of factors in the lifestyle not only can delay, but even possibly reverse, so activating telomeres for, you know, example. Yeah. So there are supplements out there. They haven't been studied much. TA 65? There's one, that's one of them. You know, I think there's always, I mean, telomerase is also

pro-cancer. So there's always that kind of, you could, you want to see, you want to see, about that, too. Yeah. You want to see the long-term studies. Cancer doesn't just take one year. They follow people on one of those telomerase activating supplements. And one year later, telomeres look good, better. So that's exciting, except for that's only one year. You don't know what's brewing, right? Cancer takes a lot. long time to develop. So there's that worry. There's the omega supplements which of course seem healthy for so many reasons, depression, inflammation. They appear to affect telomeres in a dose response way depending on how much we absorb them. So a colleague, Jan Kekyllisor, did a study on high

dose and low dose omegas. And it wasn't the dose. It was how much omegas people actually had in their blood cells that predicted telomere lengthening over four months. So it can't hurt. It's one of the few supplements that we think is good for telomeres and safe. Oh, that's interesting. Yeah. I take omega-3 for a variety of reasons. Yeah, me too. Brain health. Right. But so basically the, I think I remember this study, there was a, the blood levels omega-3 did seem to positively correlate with longer telomeres. That's right. Exactly. I can remember that. I think vitamin D. There was another one also vitamin D, correct? Where there was a sweet spot of vitamin D levels.

I think it was something like 40 to 60 nanograms per mil, which was associated with fat or two and the length as well. What about exercise in meditation? So telomerase activation. So yeah, so these lifestyle things, and Liz and I wrote a book summarizing all of the different things we know about telomeres from their biology and genetics to the lifestyle factors. and it's interesting.

I would say that there's a pretty big literature on nutrition, exercise, sleep, showing healthier levels, longer telomeres. But of course, these are correlational. So what we really want are these intervention studies in humans. How much can we really move these things around? Is it just that they're all correlated at birth? You're born with disadvantage, you have shorter telomeres, you're less likely to do all these health behaviors.

So we really need to experiment and move these things. So one study that I believe you just read, maybe just came out, was a study by Eli Peterman who took sedentary high-stress caregivers, so men and women caring for a partner with dementia. And he had them exercise for six months. At the end of six months, their stress was lower, their telomeres were longer compared to the control group. And so that's a hint. It's just one study, but it's a hint that we can improve our.

circulating immune cell telomer length. Exactly how we don't, that happened, we don't know. Is it per cell? Is it a refreshinging of naive cells in immune system? It's very crude when we do this in humans and we look at blood. We don't know exact mechanisms, but we see telomer lengthening, and that's probably a good thing. So another study, Ashley Mason just published this, we did a weight loss trial and we found that, first of all, no one really keeps off a lot a weight a year or two later, right? The people, the handful of people who kept off 10% of their weight a year later had telomere lengthening. So that was pretty exciting. And then we had the same thing for the people who kept at least 5% off. It was just less dramatic. So proof of concept study,

if you change your set point of weight, that's probably very good for a lot of your metabolic health, but including your telomer length. So that was pretty exciting because there's many meta-analysis. showing higher BMI, shorter telomerect. So what? Can we change that? Can we move that? What is it? Is insulin sensitivity? Is it really adiposity? I personally think, forget about weight. Don't get on the scale. Just look at your metabolic health, your levels of glucose and insulin. It sounds like a lot of these things that you've been describing on both ends, so the things that accelerate the telomere shortening, things that are stressful, the sugar-sweetened beverages and the different types of chronic psychological stress are also associated with types of inflammatory states, like chronic inflammation.

And the things that seem to be improving it, so the omega-3 is, you know, very known to be anti-inflammatory. Exercise is, you know, there's a very huge anti-inflammatory response to exercise, meditation. Sleep also is a part of a repair process and things like that. And lack of sleep accelerates it. So it seems as though there's, there is, you know, like you're talking about. talking about just not just looking at, you know, waist circumference, but actually looking at your metabolic health because there are actually people that are lean, but metabolically unhealthy.

And, you know, I've been involved with a few clinical trials with Dr. Bruce Ames at Children's Hospital, Oakland Research Institute. And we saw this quite often where we'd have lean people, but were metabolically unhealthy, and then we would see also the opposite. There would be people that were overweight or obese, but they were, you know, metabolically, they looked insulin sensitive. So important. And what was interesting was that some of the positive changes we're trying to get to correlated

with their metabolic status and not their waist circumference. Such an important point. We're so kind of, you know, beazzled by BMI and blinded by it. And that's not really where the action is. Yeah. Yeah, it's actually, I really, I'm glad you brought that point up. So looking at things like HP1A1C, your three-month blood glucose levels. And these glucose monitors, I mean, by next month, I hope.

hope to have one. Which one? They continue with a glucose monitor? Yeah. I'm actually trying to get one too. That's so funny. Yeah. I mean, what could be better than to know end of one, right? Like what in your, what diet do you personally respond to? Perfect. Yeah, because there are, there is definitely a very personalized response to a variety of different foods. There was a study, the Whiteman Institute, forgot his name, but senior author on it, but this was published a couple years ago in cell metabolism, where he took 800 people and he put a continuous glucose monitor on them. And then he gave them, there was a variety of foods that these people were given. So they were given simple, you know, sugars. They were given complex carbohydrates, bananas,

and they were given like fat foods that were high in fat. And then a variety of different genetic variations were looked at. So they looked at a variety of single nucleotide polymorphisms, also microbiome data. And what they found, looking at people's glucose response was that people had vastly different blood glucose responses according to their genetics and microbiomes. So important. So most people had a higher elevated blood glucose level when you're giving them carbohydrates, particularly simple ones, simple sugars, of course.

That seems very obvious, right? But there was a subset of people that had elevated blood glucose levels to fat. And that seemed to correlate with various, you know, single nucleotide polymer. And this is a company too, right? They did start some company, I believe. I don't remember what the company was. So what I've heard is it's probably one of the most sophisticated models out there for this personal monitoring, but it was developed on Israelis, so it might be really specific to them.

Right. Yeah. And the microbiome also seemed to play a role. And the one thing that was consistent for the blood glucose response was fiber. The more fiber, the lower the glucose response because it slows the metabolism and everything. You're not getting a big bolus, like you mentioned earlier in the podcast, these sugar, eating beverages, everything hits all at once. I mean, it's like, you know, you're getting a big bolus of glucose and that affects the gut, and you release inflammatory things like, you know,

like, saccharide. And so, you know, we've known about fiber. We know how important that is. And the biggest thing we have going against us in terms of what, you know, the public is eating is that that goes against the reward response, right? So the quicker, the brain can get the hit of sugar, the faster it's going to be pleasurable and addictive. just like with cocaine. And so the more fiber you have in, the slower it goes. So those processed foods, the more fiber they can take out of them, the better they sell. Wow, that's interesting.

I didn't think about it like that. Have you ever thought about looking at, like, so markers of gut health or even microbiome and the effects on telomeres, teamobiology and telomere shortening? The reason I ask that is because, well, there's a lot of interesting stuff about brain and aging and microbiome, but also psychological stress, I don't know if you're aware of this sort of field of studying the inflammatory process that happened in the gut, and like corticotropin release in hormone activates like macrophages in the gut, and that actually causes them to have an inflammatory response in this boot, this jacks up endotoxin in the blood,

which is in inflammation, right? and you're going to have activated immune cells and things like that, which would then theoretically, I would imagine, affect telomerolink, particularly if you're in leukosides, right, in blood cells. So it would be very interesting to see. Microbiome also changes with... I bet within a year we're going to see a lot of papers in this. One, that's a really common question that I hear,

which is how is leaky gut and microbiome linked to telomerelline? No one has done that study yet. But I hope many have it underway. We do in several studies now, but no answers yet. Yeah. So some of the most important takehomes, it sounds like, are the low-hanging fruit, as you mentioned. You know, healthy, healthy dye in terms of cutting out the processed foods, the simple sugars. Processed meats. Yeah, processed meats. Yeah. And then exercise, the meditation. That's something. I mean, any types of meditation? Yeah. Do you have to sit there and chant, or can you, like, is there other things?

It has to be what you like. It has to be. Or you're not going to do it, right? So the best choices you can make are the things that you're going to do every day. And you know what that is. You know, when people set their goal to, hi, and they join a gym and I'm going to go every day, it just, I mean, the data is so humorous about how many people drop out by three months of that type of thing. We have to go so far out of your way. So one, so a couple things. One is do something every day that is small and manageable that you can,

safety clip or paper clip to other behaviors, meaning that we're just predictable, you know, animals. And if it's in the maze that we go through every day, we're going to pass it. So what I mean is if it's about kind of breathing and meditation and you know that every day you have a stressful commute, you should use part of that, use an audio, use traffic, use things to cue you to be practicing your mind-body activity. So that's why. example. Another is, you know, if it's exercise, when in the day can you get in 10 minutes of vigorous walking? And is it to your car? Is it during your lunch break? So things that you do every day staple some of these healthy habits to it. It doesn't have to be a big, long workout.

We know from our research from large population-based studies that small, moderate health behaviors add up over decades to be, to mean better longevity, longer telomeres, lower inflammation, all those kind of intermediate things we think matter. Yeah. So I think the, you know, one of the studies that we did showed that high stress caregivers have shorter telomeres if they're sedentary, but not if they're active. And by active, that was around 10 minutes a day of kind of vigorous walking. Wow, that's not very much. Let's do it. Yeah. Is there a research that indicates that there is a dose-dependent effect on exercise intensity and telomere length, though?

Yes, there is, but it's not linear. So when you get up to extreme sports and marathon runners, yeah, they're a little bit longer and they're telomeres, but not much longer than someone who's like running three times a week. So we don't think, you know, these extreme things, they also have some costs and we don't think that they're necessary in terms of some of the aging biomarkers that we've been studying. Now, there are biohacks and lifestyle hacks, and that is a super exciting.

interesting area that hasn't been studied. Again, there's going to be some risks, but some probably better benefits than some of the drugs we've been talking about. So by that, I mean the intermittent fasting, extreme breathing, some of the things that you've featured on your podcast that are more. Has intermittent fasting been shown to? No one's looked at that yet. I'm sure that's in progress, right? It's got to be, wow. So yeah, not that you're aware, so yeah, that would be... Yeah, I mean, not with telomeres. I'm sure they looked at it with other...

Yeah, other aging biomarkers, for sure. And certainly, like, the mitochondrial health, like you mentioned earlier. Yeah. But cool. So the meditation. I mean, I think that for some people, they cannot stand to sit. It's not going to be sitting meditation. And that's okay.

Yes, we study it to death. Mindfulness is in the news every day. Go to your... We're in October. In your magazine stand, when you check out, is a special issue of time. on mindfulness. And it has one of our studies, this meditation retreat study where it looked like people, telomeres really benefited from a three-week residential retreat. That's exciting and especially benefited if they were people who are particularly neurotic, if they kind of have a lot of,

you know, tendency for negative emotions. So people, they benefited from their baseline, you mean? We see lengthening. We don't want to like be like, you can lengthen your telomers because like, how how do they lengthen in three weeks? We don't know. Right. But it looks. We see a train, we see lengthening. We don't want to, like, we good. So that's for people who love meditation. Try it. You know, if you, if you haven't tried it, try it, because it can only benefit you if you like it and it can become a habit. But there's other things. So like, for me, it's yoga. Like, it's got to have the movement in it. And there, so people need to have, you have to have some vigorous activity. It can be walking. You should have some mind-body activity that changes things. It's restorative. It's not the same as an aerobic

exercise and that turns on, we think, things like vagal tone and more restorative processes. What's vagal tone? So heart rate variability. Oh, okay. And then, you know, I think positive stress should be part of the menu. We don't really think about that much, but like we're doing a study now where we're, you know, comparing things like high intensity interval training to extreme breathing and meditation. And it's like, these are really different, but we think they're going to benefit these

aging processes in different ways. And we want to see what those ways are. Yeah. Excellent. You know, one of my meditation, at least for a long time, sort of my favorite thing to do for meditating would be a long run. Yeah. Like, I can't, I'm not one of those people.

For sitting still and like just trying to do the breathing, it's hard for me. But like going for a long run, my mind, I go into the zone. Yeah. And it really is very refreshing for me. I recently, after having my son, I got into this high. intensity, interval training, these spin classes, which are an hour long, and an amazing workout, certainly more low impact. But one difference I do notice between the two is that I don't have the mindfulness that I had

with the run. After the run. So, yeah, because, well, just, you know, there is points where I do get in the zone, but, you know, it's a little different, doing the high intensity stuff. Yeah. It's a little, I'm not so, it doesn't seem so, I'm not getting in that zone like I do on the long run. So it's kind of like I need to incorporate both. Yeah.

And the other thing I wanted to quickly just, I know we talked a little bit about this off camera was, you know, people are interested in measuring different biomarkers and particularly at baseline and after they make changes. And it just sort of, you know, biomarkers of aging in particular are interesting to look at. And there aren't a lot of consumer available ones, unfortunately. I was talking to you about DNA damage and how it's an assay that I had worked on actually for several years. There was a startup company a few years ago that was trying to measure DNA damage for consumers, but it sort of dwindled away and it doesn't exist anymore. So I know there is a company, you know, that you can measure your TLM or length. Do you think those things are sort of, you know, how accurate can we really,

imagine some of these tests to be when you're, you know, sending blood samples, for example, in there, you know, I mean, is it something that, is it the end-all be-all? Would you decide to sort of say, take it with the green salt if you're doing something like that? That's exactly what I would say. I think it's so interesting to be able to monitor ourselves, but if you're going to do it, number one, you've got to be educated on how seriously should you take it, how accurate is the test, what does the result really mean? So, telom are testing. There's at least four companies and it's an interesting idea and some people are going to do it and they want to know. So if you want to get your telomers tested, know about the issues there of what the different

tests tell you. I mean, I'll tell you right now. They don't tell you that much individually about your risk because the risk we know from them is about population-based studies. So if you want to measure it, keep monitoring it, right? Because that's what matters is like, am I? am I able to change it and with what? So I think that's probably the bigger use of them.

Liz Blackburn and I wrote up the issues with testing that we feel people should be aware of. Not that we're saying you shouldn't get tested, but just like know that if you have really long telomeres, the next time you get tested, they're probably going to shorten more than someone who started off with short telomeres. Long telomeres shorten faster.

Short telomeres are really stable. If you have really short telomeres and they change a lot, that is not a great. profile, how seriously issues should take that, know that there's error, get retested. It can be upsetting. And so there's that risk involved, right? So I personally know, I mean, I just think about this stuff too much. I don't really want to know my personal TILMere-length results. I already know they're probably short and I already know what to do. Yeah. Well, I was telling you, I tried one of the companies, you know, of course I was doing this four months after I gave birth to my son and I

I was waking up four times a night to nurse him. I was literally getting no sleep. And I measured, usually, it was pretty much my chronological age, is what my biological age by Ticimer length was calculated to be. And then I did it three weeks later. And it had taken me 20 years, aged me 20 years. Yeah. And I just felt like that didn't.

You aged 20 years. In three weeks. So, Rhonda, what could happen? You as a lab person, bench person, what could have happened to your blood? Well, I certainly think some, some oxy years. oxidative stress damage at room temperature could have caused them like that. So I do think that is important for people to keep in mind that there are technical issues as well where, you know, these things are being shipped to a lab somewhere and depending

on where they're, you know, how long they're at the post office and, you know, all, there's all sorts of things going on. So it's certainly like, I think that's important to keep in mind. So the FAQ I was mentioning is on my website, which is AME Center. UCSF. AME is Aging Metabolism Emotions Center.org. And if you click on telomere effect,

you'll see, what about telomere testing? We list the labs, we list all the pros and cons. So that's a place for people can learn more. Yeah. You also have a book. Yes, and we put a free chapter of stress in telomeres on that same webpage. And the book

is, you know, it's for the public, but it's completely science-based. So What's the title of the book? The Tealemir effect. The Tealemir Effect. And this was co-authored with Elizabeth Blackburn? Right.

Okay. And you're also on Twitter? Yes. And I'm learning so much by following you, Rhonda. My Twitter is Dr. underscore Eppel. Dr. underscore EPL. Perfect. Anything else?

It's so, it's such a pleasure to talk to you. Thank you for sharing such solid information with the public. Thank you. this huge range of topics and thank you for including me. Thanks for the discussion. It was really nice to speak with you. Thank you. Thank you so much for listening and so much to Dr. Eppel for coming on the podcast and sharing so much great information on telomere science and more. Dr. Eppel can be found on Twitter and is a great follow. Her username on Twitter is DR underscore EPL. That's D-R-U-E-L. She has a really great presence over there, so make sure to go check her out. Also, don't forget to check her. Also, don't

out her best-selling book, The Telemere Effect, which she co-authored with Nobel Prize winner, Dr. Elizabeth Blackburn, available now at all major bookstores. If you enjoyed this episode, make sure to check out the highlight clips. You can find all of those moments at foundmyfitness.com forward slash clips. These are a newer resource and pretty awesome, especially if you have a specific concept you want to pass along to a friend. All of these over-the-top, in-depth resources are made available to the wider world thanks to the amazing financial support of my monthly supporters. To join my crew of voluntary monthly supporters, head over to foundmyfitness.com forward slash crowd sponsor. Once again, that's found my fitness.com forward slash crowd sponsor, C-R-O-W-D-S-P-O-N-S-O-R.

Finally, if you were interested in some of the SNPs that are associated with either shorter or longer telomere length and you have a consumer genetic data file from a service like 23 and me, you can run the TELAMere report at foundmyfitness.com forward slash genetics. That's it for now. Until next time.