Rhonda: Hello, everyone. I'm sitting here with Dr. Elissa Epel, who is the director of the Aging Metabolism and Emotion Center, and a 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.

Elissa: Yeah, so one way to look at aging is to see when people die, a little more fine-tuned 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, you know, how well functioning are our mitochondria, what's our epigenetic clock?

So there's these mechanisms that we can measure and look at in the cell that are active 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 this aging biology is kind of elastic. So some people's aging biology processes 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.

Rhonda: 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 some 8 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.

Elissa: Yes, Daniel Belsky's work, right. So this is a really big, important trend in our field, which is to look 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 till people get disease. We know that aging is one of the main causes of later diseases except for the genetic diseases.

Rhonda: So it sounds like you're also talking a lot about differences between someone's life span, how long they live and their health span, how healthy they are.

Elissa: 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 expectancy 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, taken 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, etc. So that's the kind of double-edged sword of living long. So what we really want to focus in 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.

Rhonda: Right. So delaying age-related disease, delaying cardiovascular disease, delaying neurodegenerative diseases. You mentioned delaying cancer, like having all those things where you're basically improving the quality of life as opposed to just sort of, you know, increasing how long you live but just living kind of a degenerative kind of lifestyle.

Elissa: Yeah, and it's a whole formula. So it's not one thing. Like, the levers that control aging are the things that we know about but we easily forget. So we often hear, you know, about the lifestyle things. 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. You know, like smoking, and sitting too much, and you know, leaving stress unchecked, and just having years and years of feeling vigilant and not getting enough sleep. So there's a lot of low hanging fruit that we know about. And then there's some things that we don't know about or that 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 systems, short term, activating things, psychological or physiological. And then also like the web of social connections that we have, the more positive they are and the more we feel supported, those are really important predictors of longevity too.

Rhonda: 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, you know, background on what telomeres are, and why they are involved in the aging process, why they're biomarkers for aging?

Elissa: Sure. So people like to think of them as like the aglets of the tips of shoelaces, this plastic caps to keep shoelaces from fraying. So when you think of our linear chromosomes, they're all capped at the end with this wound up strings of DNA, repeating DNA called telomeres. And 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 cells 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 tied up intimately.

Rhonda: They take the hit, so they're trying to protect your DNA from potentially acquiring a mutation that could lead to something like cancer.

Elissa: Yes.

Rhonda: So they sort of take the hit for the cell?

Elissa: Right.

Rhonda: In your experience, how much would you say that telomere length...so, you know, 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 is just biomarking the aging process?

Elissa: 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 it to the telomeres 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.

Rhonda: So it sounds like the telomeres are much more important in stem cell populations, populations that are really responsible for replenishing a variety of cell type including tissue.

Elissa: Right, absolutely.

Rhonda: 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 non-stem cells?

Elissa: 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 in telomere length 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.

Rhonda: 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?

Elissa: Right.

Rhonda: Talk a little bit about that enzyme, but it's not active in every cell, correct?

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

Rhonda: And telomerase, if I remember correctly, it's more active in stem cells than in somatic cells, for the most part?

Elissa: Yeah, so at UCSF, my colleagues, Jue Lin actually has an assay. It's very sensitive and can measure the level of telomerase 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.

Rhonda: Interesting. So you mentioned this sort of potentially double-edged sword in terms of the, you know, the telomeres getting critically short and telomerase activity going down and that leading to cellular senescence. We've had Dr. Judy Campisi on the podcast, we've talked a lot about senescence, or even apoptosis, or you said they can become immortal when telomerase becomes overactive. So basically, it's just constantly rebuilding the telomeres, and immortality in some cases with overactive telomerase is associated with certain types of cancer.

So what would you say like, you know, measuring...you just talking about measuring telomerase activity in white blood cells and that's sort of a marker for, you know, how well a person is aging or how well the cells are aging. Is there like a threshold for when it becomes too active and it's like a cancer cell? Like can you detect the difference like when it's like always active?

Elissa: So in our research, we always make... we're not measuring any cancer cells otherwise... I mean, they're 10 fold higher in telomerase so...

Rhonda: 10 fold.

Elissa: So it would mess up our measures, yeah. So it becomes in cancer cells...

Rhonda: It's kind of what I was asking. Like, what degree...

Elissa: It becomes like out of the physiological normal range. So it is true 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. Yes, so, you know, this is a... telomere 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 in the blood, long telomeres also predict greater risk of certain cancers. like glioma, melanoma, and several others. So you know, it's homeostasis, its physiology. You want to be long but not as extremely long if you want to kind of have the best ratio of low risk for degenerative diseases like dementia and heart disease, and low risk for cancer.

Rhonda: Definitely the complexities of telomere length always sort of fascinated me, particularly because rodents which don't have a very long lifespan, their telomeres are so long.

Elissa: Yes. Right.

Rhonda: So I never quite understood that, you know, what's going on there but...

Elissa: They're just not a great model for humans because they don't die of short telomeres, unless you're like genetically manipulating them too short.

Rhonda: Exactly. And there are some human diseases where telomeres are short and that does have a progeria type of effect, like Werner.

Elissa: Right. So that's super interesting. So in these certain handful of genetic disorders, where people might have half a dose for telomerase, so their telomeres shorten quickly, they develop diseases that are... You know, the diseases 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 transmit, you know, the mutated gene to offspring and they get the aging syndrome. They also can transmit just the short telomeres epigenetically, like in a direct epigenetic way...

Rhonda: That's interesting.

Elissa: To the offspring. 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.

Rhonda: So let's talk about the environmental things that are regulating telomeres. So we just talk about genetics things, you know, various environmental stressors, good or bad.

Elissa: One last point about genetics. So you were you earlier asked, like, is this a marker 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 to 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 that was those kind of Mendelian randomization studies are one of the best ways that we can say there's a direct physiological connection here.

Rhonda: Right yeah, I didn't know there was any Mendelian randomization studies on it. That is very interesting. So cardiovascular disease and dementia are two one's health outcomes that seem to be effective.

Elissa: Right. And then as I said the higher cancer risk for some of these.

Rhonda: So different types of environmental things that can affect aging, a lot of focus of your research has to do with various types of stress. Whether it's diet related or it's psychologically related stress.

Elissa: Right. So one way to think about all of those environmental things is to think about the exposome, 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 exposome. 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 telomeres, all of the ones that 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 BPA and Roundup. And these, a lot of these chemicals in plastics, etc., 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.

Rhonda: Yeah, I think I actually read a... skimmed a recent publication of yours with the cadmium.

Elissa: Yes, the metals.

Rhonda: The lead.

Elissa: So who knows.

Rhonda: I mean, we're exposed to that in chocolate and rice. I mean, that stuff is definitely...

Elissa: Oh, yeah, arsenic.

Rhonda: Arsenic, right.

Elissa: 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 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 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 milieu and those are related to shorter telomere.

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.

Rhonda: And it was quite a bit of coffee, right.

Elissa: Yeah. We just enjoy a mixed latte.

Rhonda: Back to the sugar-sweetened beverages you mentioned because I did read that study, 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 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. And so that was quite disturbing.

Elissa: Right. You know, that sugared beverage finding has been replicated many times by now. And it's not surprising because liquid sugar has been more of an effect than sugar in food. It does cause, you know, a big metabolic disturbance immediately. And so if you're drinking that every day, you should expect to have...across the spectrum of aging biomarkers to have them be accelerated. And so, 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... this university banned all sugar beverages. It's because... I mean, it's just so ridiculous.

Rhonda: That's awesome.

Elissa: Yeah, it's awesome, it's amazing.

Rhonda: Go UCSF.

Elissa: 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... so bottom line is that it reduced drinking dramatically, and it reduced waist size just getting rid of it at work. People could still have it at home, they can still bring it to work. So those are kind of things...

Rhonda: Limiting the access.

Elissa: 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.

Rhonda: Right. I remember reading... and this was an animal study where should these sugar-sweetened beverages activated dopamine pathways and like a reward pathway in the brain. Similar to like some very bad recreational drugs. I mean, not the same...it wasn't as robust but like Methamphetamine. I mean these things. And I mean, you know, that is definitely I would say pretty scary that there's an addictive aspect to the sugar as well.

Elissa: 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.

Rhonda: And I think you just brought up a really good point. I mean, if medication is doing one thing where it's sort of like maybe extending a couple of years of your life because you're not gonna 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 asleep.

So it is really important to address, you know, the problem, what's causing you to, you know, be at a higher risk for type two 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 gonna be improved ...

Elissa: That's right.

Rhonda: ...if you don't fix it.

Elissa: 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 the hedonic addiction, that Metformin is doing 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.

Rhonda: 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 associated 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 have shorter telomere. 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 talk a little bit about that.

Elissa: 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, 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 stressors that we have as adults which are things like caregiving, or job stress, or domestic violence in relationships, so things that go on for years and years. So those are the types of things when we do see telomere shortening and inflammation. And all the rest like work stress is not related to telomere shortness.

Rhonda: Really?

Elissa: 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 that 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 gonna show up as much or more consistently, you know.

Rhonda: That's good to know. What about rumination when you're like constantly thinking about something that's maybe...

Elissa: So I would say that rumination is part of chronic stress. That is when things happen and we carry it with us, moment to moment, day to day, where can we keep ourselves in a stress state. So 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 know, you can't be present and be ruminating at the same time.

Rhonda: Right. So you think that... because you know, oftentimes, you know, with something high stress, if I'm working on a project, definitely work-related, I do tend to ruminate. But I mean, it's not like, I'm ruminating on it for a year, so that...do you think there is 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, versus like a very traumatic type of stress that's like, you know, the financial stress or something?

Elissa: I think that 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 perceptive cognition or perseverative perceptive thought processes, they have accelerated biomarkers of aging, telomere length, and inflammation. So what is that?

Rhonda: What is that type of...

Elissa: 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's should be a 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're already in a stress state. Their cortisol is higher.

Rhonda: That's what I was gonna ask. Are there any other type of markers?

Elissa: Whereas some caregivers wake up and they feel positive, they're looking forward to the day. They feel joy. They look better in their telomerase enzyme, in their cortisol. So waking up states are really important to notice.

Rhonda: So like a pessimistic view versus optimistic could you kind of simplify that as?

Elissa: 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 shorter telomeres, 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, you know, that's my pessimistic thought, that's how I work.

Rhonda: I actually find that a good workout, a very good like, you know, if I do a really hard intense run, or a sprint, or a 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 it helps alleviate that.

Elissa: Yes, absolutely. Your N of 1 is also been shown up in, you know, studies of exercise and studies by Eli Puterman 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 ask partly because we're at a meeting here on women's health and I've just, you know, recently been scouring the human literature trying to understand hormones, and aging, sex hormones. And what have you learned?

Rhonda: It almost never comes up and it's certainly a question that has remained unanswered in my mind for several years. And, you know, over the years I've heard a variety of hypotheses, you know, ranging from immune system differences to differential effects of testosterone on a variety of different tissues, particularly the immune system. But it... You know, you started out this podcast, you mentioned the average lifespan in United States for men was about 78 something and women was about 83, you said. And I did want to stop and ask you right there why? Why is that?

Elissa: So I've recently tried to read everything I could about this, to understand it. So this sex gap in longevity is robust across cultures across countries. I mean, this is a fundamental thing about human biology.

Rhonda: Species yeah.

Elissa: Women live longer, why? You know, it's kind of obvious of like, well, there's two X chromosomes, there's something protective about that backup copyies. 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 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. Examples, women have much longer telomeres, like hundreds 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 length, so there's probably a masculinization 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 energies 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 these beautiful models 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.

Rhonda: Are there any people that are really specializing in that field that you know about?

Elissa: 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 life span, meaning your menopause is a lot later, you're likely have longer telomeres. If you give birth later, like in your 30s instead of your 20s, sorry, your last birth, you have longer telomeres. Those are also related to longevity too, having the longer reproductive life span.

So there are clues, like this is really important, we should understand the sex differences. They're big, they're obviously related to hormones but we really don't actually...don't know how to act on them. We don't know you know...

Rhonda: I didn't know that the differences in telomere length between men and women were present at birth or male and female.

Elissa: 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 telomere length at birth is impacted by the mom's health, her mental health, her nutrition, her physical health. So that's another whole world of like fabulous, important knowledge for us to act on.

Rhonda: 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 a caregiver, 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. 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?

Elissa: 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, telomere length, the immune system, how much it's prime for inflammation, those are so important at birth. 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 shorter telomeres at birth in the cord blood. So that one has become...

Rhonda: What kind of stress during pregnancy?

Elissa: 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, mourning, 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 health through epigenetics. And so now that we know that there's, you know, important epigenetics the 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.

Rhonda: 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, you know, it's my life. But when you start to think about your unborn child, I think people become a little more...

Elissa: Oh, so motivated.

Rhonda: Motivated.

Elissa: So you with your immense knowledge on aging, what did you change when you got pregnant? Did you and your husband do anything differently?

Rhonda: We've been really focused on good nutrition and good lifestyle for quite 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 these studies in humans. But there was a study published a couple of years ago, I don't know if you've read it, I don't remember, it was one of the top journals like in Sscience or Nnature or maybe Ccell. But what was looked at was sperm DNA in men that were obese and men that were not obese, so healthy men. And there was a variety like over 500 genes were changed in terms of like how their expression right, so their epigenetic were changed. And a lot of these genes had to do with metabolism, had to do with cognitive function.

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 were like. So it was really...

Elissa: Amazing.

Rhonda: A very interesting kind of pilot study indicating there definitely seems to be a causal like, you know, obesity is changing a lot of the way these genes are in sperm DNA. Which is what you're passing on.

Elissa: Oh my God.

Rhonda: And there's tons of studies...

Elissa: Huge.

Rhonda: Showing male mice that are obese have offspring like female offspring that get type one diabetes because they get like an autoimmune thing. Or, you know, so there's been lots of animal study, of course, you can only translate so much of that. So I felt like that human study was a really, you know, a good pilot study to really kind of show this is happening in humans. You know, and certainly make people think men aren't off the hook either, you know. And that's oftentimes are, you know, I think that I'm not sure a lot of men are aware of the fact that their lifestyle actually does matter.

Elissa: Right. They're becoming more important than we think.

Rhonda: Right. And the telomere length and the DNA, or the sperm cells that also plays a role in offspring as well or do we know that at least from animal studies?

Elissa: 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 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 that a covariate covariance. That's something that shapes telomere length.

Rhonda: And what's the effect in the offspring? Is it shorter or longer?

Elissa: Longer.

Rhonda: So longer and...

Elissa: So sperm telomere length is longer and that can affect the offspring telomere length to be longer.

Rhonda: Are there studies that have looked at whether or not having a longer telomere length to start predicts, you know, healthy aging or?

Elissa: 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 partly prenatal environment and, you know, health of mom and dad and their germline, you know, epigenetics. So that is one of the biggest determinants of their telomere length in late life. 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.

Rhonda: So you guys going to look at that?

Elissa: Yeah, I mean...

Rhonda: Someone should.

Elissa: Yes, absolutely.

Rhonda: And not just lifespan but like you said, you know, look, does it predict cardiovascular disease, does it predict dementia?

Elissa: 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, mid-life determines older health. So now they fund studies of mid-life. And they even funded us and our colleagues to look at pregnancy now, to see telomere length, how it's transmitted and affected at birth from social and economic disparities, race, sex, stress, how all of those shape telomere length 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.

Rhonda: It's kind of like having runway, right, you want to have something to start with. But you also just...I've just thought of an important factor with a lot of nutrition studies that are looking at telomere length and, you know, 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 you know, they're... maybe they have a lower socioeconomic you know, background so they can't afford.

Elissa: And it is a factor. Education...

Rhonda: 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.

Elissa: Yes. So, it is, it has to be a covariatecovariant and chronological age has to be a covariatecovariant, 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...

Rhonda: So the more educated, the longer the telomeres or?

Elissa: Yes, exactly, positive correlation. My colleague, Janet Wojcicki, 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. But those who did not graduate high school had babies with shorter telomere length. So we couldn't figure out anything that could explain, the covariance, you know, everything we could and they are all low income. So the education is probably filtering in so many different ways of promoting better health.

Rhonda: You’re making me feel good about my Ph.D. So to just 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 one 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, you know, what sort of factors in the lifestyle not only can delay but even possibly reverse, so activating telomerase for example?

Elissa: So there are supplements out there, they haven't been studied much.

Rhonda: TA-65.

Elissa: 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 want to see...

Rhonda: I've been concerned about that.

Elissa: You want to see the long term studies. Cancer doesn't just take one year, they follow people on one of those telomerase activation 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 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, Janice Kiecolt-Glaser, 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 the 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.

Rhonda: Oh, that's interesting. I take omega three for a variety of reasons, you know.

Elissa: Yeah, me too.

Rhonda: Brain health. So basically, I think I remember the study. The blood levels omega three did seem to positively correlate with longer telomeres.

Elissa: Yeah.

Rhonda: That's right.

Elissa: Exactly.

Rhonda: I remember that. I think vitamin D...there was another one also with 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 better telomere length as well.

Elissa: Important hormone, yeah.

Rhonda: What about exercise and meditation, so telomerase activation.

Elissa: So these lifestyle things...and Liz 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 Puterman, 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, you know, it's just one study but it's a hint that we can improve our circulating immune cell telomere length. Exactly how that happened, we don't know. Is it per cell? Is it a refreshing of naive cells in the 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 telomere 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 of weight a year or two later, right? 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 a 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 telomere length. So that was pretty exciting because there's many meta-analyses showing higher BMI, shorter telomere length. So what? Can we change that? Can we move that? What is it? Is it 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.

Rhonda: 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, this sugar-sweetened beverages and the different types of chronic psychological stress, are all 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 and meditation. Sleep also is a part of the repair process and things like that. And lack of sleep accelerates it.

So it seems as though there is, you know, like you're talking about just not 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...metabolically they looked insulin sensitiveity.

Elissa: So important

Rhonda: 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.

Elissa: Amazing. Such an important point. We're so kind of, you know, bedazzled by BMI and blinded by it. And that's not really where the action is.

Rhonda: Yeah, it's actually a really...I'm glad you brought that point up. So looking at things like HbA1c, your three-month blood glucose levels.

Elissa: And these glucose monitors, I mean, by next month, I hope to have one. But like to able to...

Rhonda: Which one, the continuous one glucose monitor?

Elissa: Yes.

Rhonda: I'm actually trying to get one too. That's so funny.

Elissa: I mean, what could be better than to know...

Rhonda: To know what you...

Elissa: End of one right? What diet do you personally respond to?

Rhonda: Perfect. Yeah, because there is definitely a very personalized response to a variety of different foods. There was this study, I think the Weizmann Institute, I 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 are given simple, you know, sugars, they were given complex carbohydrates, bananas, and they were given like 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 microbiome.

Elissa: So, important.

Rhonda: So some people, 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 polymorphisms.

Elissa: And this is a company too, right?

Rhonda: They did start some company I believe. I don't remember what the company was.

Elissa: Yeah, what I've heard is it's probably one of the most sophisticated models out there for this glucose monitoring, but it was developed on Israeli, so it might be really specific to them.

Rhonda: 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-sweetened 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, lipopolysaccharide.

Elissa: Right. 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 all 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.

Rhonda: Well, 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 biology 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 happen in the gut and like corticotropin-cortical tropic releasing hormone activates like macrophages in the gut, and that actually causes them to have an inflammatory response, and this jacks up endotoxin in the blood, which is an inflammation, right? And you're going to have activated immune cells and things like that, which would then theoretically, I would imagine affect telomere length. Particularly leukocytes, right, in blood cells. So it would be very interesting to see microbiome also changes with...

Elissa: Absolutely, Rhonda. 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 telomere length? No one's done that study yet. But I know many are...

Rhonda: It's interesting

Elissa: Have it underway. You know, we do in several studies now, but no answers yet.

Rhonda: So some of the most important take-homes it sounds like are the low hanging fruit, as you mentioned, you know, healthy diet in terms of cutting out the processed foods, the simple sugars definitely...

Elissa: Processed meats.

Rhonda: Yeah, processed meats, and then exercise, the meditation that's something... I mean, any types of meditation do you have to sit there and chant or can you like... is there other things?

Elissa: 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 that is when people set their goal too high and they join the 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 when you have to go so far out of your way.

So a couple of things. One is do something every day that is small and manageable, that you can safety clip or paperclip 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 one 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 the 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 mean better longevity, longer telomeres, lower inflammation, all those kind of intermediary things we think matter. 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.

Rhonda: Wow, that's not hard to do.

Elissa: That's not that much. Let's do it.

Rhonda: Is there research that indicates that there is a dose-dependent effect on exercise intensity and telomere length, though?

Elissa: 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 in their 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, you know, the things that you feature on your podcast that are more...

Rhonda: Has intermittent fasting been shown to...?

Elissa: No one's looked at that yet.

Rhonda: I'm sure that's in progress, right?

Elissa: I don't know.

Rhonda: It's got to be. Wow. So yeah, not that you're aware of. So yeah, that would be...

Elissa: I mean, not with telomeres. I'm sure they've looked at it with other...

Rhonda: With telomeres. Yeah, other aging biomarkers for sure. And certainly like the mitochondrial health, like you mentioned earlier. Yeah. But cool, so...

Elissa: So the meditation 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 studied 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 looks 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.

Rhonda: So, people, they benefited from their baseline, you mean?

Elissa: We see lengthening, we don't want to be like, you can lengthen your telomeres. Because like how the hell do they lengthen in three weeks, we don't know. But it looks good. So that's for people who love meditation. Try it, you know, 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. 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.

Rhonda: What's vagal tone? What do you mean?

Elissa: So heart rate variability. 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 this 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.

Rhonda: 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. Like 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 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 were an hour long and 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.

Elissa: After the run.

Rhonda: So yeah, because...

Elissa: Or during.

Rhonda: Well, you know, there is points where I do get in the zone but, you know, it's a little different than doing the high-intensity stuff. And 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...

Elissa: Really interesting.

Rhonda: Incorporate both. 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 just sort of, you know, biomarkers of aging, in particular, are interesting to look at. And there aren't a lot of consumer available one, unfortunately.

I was talking to you about DNA damage and how as an assayasset, 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 in, you know, 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 telomere 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, and they're... I mean, is it something that... is it the end all be all? Or would you sort of say, take it with a grain of salt if you're doing something like that?

Elissa: 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 telomere 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 telomeres tested, know about the issues there of, you know, 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 risks 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 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, you'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, you know, that is not a great profile. How seriously you 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 telomere length results. I already know they're probably short and I already know what to do.

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

Elissa: You aged 20 years.

Rhonda: In three weeks. So I think I like the...

Elissa: So Rhonda, what could happen? You as a lab person, a bench person, what could have happened to your blood?

Rhonda: Well I certainly think some oxidative stress damage at room temperature could have caused something like that. So I do think that is important for people to keep in mind that there are technical issues as well. Where these things are being shipped to a lab somewhere and depending on how long they're at the post office and there's all sorts of things going on. So it's certainly like...I think that's an important thing to keep in mind.

Elissa: So the FAQ I was mentioning is on my website which is amecenter.ucsf. AME is aging metabolism emotions center.ucsf. 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.

Elissa: So that's a place where people can learn more?

Elissa: Yeah.

Rhonda: You also have a book.

Elissa: Yes. And we put a free chapter of stress and telomeres on that same web page. And the book is, you know, it's for the public but it's completely science-based.

Rhonda: What's the title of the book?

Elissa: "The Telomere Effect".

Rhonda: "The Telomere Effect", and this was co-authored with Elizabeth BlackburnBalckburn.

Elissa: Right.

Rhonda: And you're also on Twitter?

Elissa: Yes, and I'm learning so much by following you, Rhonda. My Twitter is Dr_Epel E-P-E-L.

Rhonda: Dr_Epel, E-P-E-L perfect. Anything else?

Elissa: So it's such a pleasure to talk to you. Thank you for sharing such solid information with the public on...

Rhonda: Thank you.

Elissa: ...on this huge range of topics and thank you for including me.

Rhonda: Thanks for the discussion. It was really nice to speak with you.

Elissa: Thank you.