Ovarian Longevity with Dr. Jennifer Garrison, PhD

Today I'm speaking with Jennifer Garrison, PhD, about her groundbreaking research on ovarian aging and its implications for female health. She emphasizes the importance of understanding the brain-ovary connection and how ovarian health impacts overall health span. Our conversation highlights the need for more research in female physiology, the challenges faced in the field, and the exciting innovations on the horizon for women's health.

Jennifer Garrison, PhD, is a renowned scientist specializing in the study of aging and female reproductive health. Her work focuses on uncovering the intricate connections between the brain and ovaries, aiming to improve health outcomes for women as they age. Dr. Garrison is a leading voice in advocating for increased research in female physiology and is at the forefront of developing innovative solutions for women's health issues.

Timestamps

00:00 Introduction to Longevity and Female Health

05:07 The Science of Ovarian Aging

09:54 Understanding the Brain-Ovary Connection

14:58 Research and Innovations in Female Health

20:05 Future Directions in Ovarian Health Research

27:05 The Importance of Biomarkers in Women's Health

30:26 Understanding Biological Age and Its Implications

31:18 Empowering Women Through Knowledge of Their Physiology

33:34 Diet, Exercise, and Ovarian Health

34:56 The Role of Hormone Therapy in Women's Health

38:10 Genetics and Menopause: What We Know

40:59 Funding Challenges in Women's Health Research

51:21 Innovative Fundraising Ideas for Women's Health

Transcript

[00:00:00.280] - KAYLA BARNES-LENTZ

Welcome to the Longevity Optimization podcast, where we discuss longevity, optimal health, nutrition, peak performance, cognitive excellence, and so much more.

[00:00:10.950] - KAYLA BARNES-LENTZ

All right, Dr. Garrison. It's such a pleasure to have you here with me today.

[00:00:14.030] - JENNIFER GARRISON, PHD

Nice to meet you, finally.

[00:00:15.350] - KAYLA BARNES-LENTZ

Yes, I know. This is probably a topic that I'm most excited about.

[00:00:21.030] - JENNIFER GARRISON, PHD

Okay, well, me too.

[00:00:21.860] - KAYLA BARNES-LENTZ

All the things. You're doing incredible work at the Buck Institute, and you're really focusing on female ovarian aging. I would love if you could talk a little bit about your background. I know you started really with the brain, but this has led you now to female reproductive health.

[00:00:40.170] - JENNIFER GARRISON, PHD

Exactly. So true. I'm actually a chemist. My PhD was in chemistry, and then my postdoctoral work was in neuroscience. When I started my lab, I have my own research group at the Buck Institute. When I started at the Buck Institute, I was thinking about aging. Buck, obviously, is an independent academic research institute that brings together scientists and clinicians across lots of different disciplines to study mechanisms of aging. When I came to thinking about aging, I was like, I'm not so interested in the downstream consequences. There's plenty of people working on that. How do we remediate once the damage is done? Rather, I was really focused on what are the very first dominoes to fall? What's the most upstream stuff that we can think about to target with respect to systemic aging. My work, my training was really around neural circuits and behavior. Thinking about the part of the brain that I call, well, that mediates the mind-body connection. So thinking about how does your brain, which truly is like the master regulator of your whole body, how does your brain talk to the rest of your body? Because it's constantly, it's both dictating what's happening, but then it's constantly listening to and integrating feedback.

[00:02:02.860] - JENNIFER GARRISON, PHD

There's this two-way chemical conversation that's going on. That's really what sets up all of your homeostatic systems, all of the things that keep you alive. So like body temperature, fluid and energy, homeostasis, circadian rhythms, but also reproductive function. When I started, the part of the brain that I think of as the coolest part of the brain, even though it's really from the From the neuroscience perspective, it's not as exciting as the cortex and consciousness. It's the part of the brain called the hypothalamus, which is ancient, and it's really deep in your brain. If you triangulated here, almost as deep as you could possibly go. It's like the size of a grape in a human. This is where the neurons that control those circuits that control homeostasis are located. With age, obviously, there's inflammation that occurs everywhere in your body with age that goes up. But in your brain, it's not uniform. In your brain, it happens in particular hotspots. Hypothalamus is one of those hotspots. Just during normal aging, inflammation goes way up in your hypothalamus. This is also the place that I think of it like the brain's WiFi. It's making and using a lot of these long-range chemical signals that we sometimes call hormones.

[00:03:33.260] - JENNIFER GARRISON, PHD

Hormons is like a loaded word because it's a very vague word that just means any chemical moiety. It could be a protein, a peptide, a lipid, a small molecule, A gas. Any chemical, really, that mediates communication between two sites that aren't connected. It could be distant tissues, it could be cells that are nearby each other but not actually connected. Anyway, this part of the brain makes tons of these hormones that travel back and forth and that mediate this WiFi. I thought, well, maybe that age-related inflammation is changing the way those neurons that control homeostasis are said or are talking or receiving information, and that that might be some of the things that we think about that happen during normal aging. When you think about what happens to a body over decades during normal aging, the things that change are exactly those homeostatic systems, energy and fluid homeostasis, circadian rhythms, body temperature regulation, and reproductive function. Reproductive function is one of the earliest things to change. I'm sorry, that was a long-winded way of saying that's where we started. I love that. We were hunting down the mechanism by which one of these long-range signals impacts aging and that brought us to the reproductive system.

[00:05:03.470] - JENNIFER GARRISON, PHD

That's not where we meant to go, but that's where we ended up. About six years ago, we had a donor come to us and ask at the Buck Institute if we would start a center to study aging in the female system through the lens of those organs that we call reproductive organs, but I would love to stop calling them that. What should we call them? We should call them ovaries and fallopian tubes and uterus. Okay. Because I think calling them reproductive organs has allowed all of history, everyone for the last century, to really pigeonhole all of women's health through the lens of fertility and make it small. When what we're talking about is half the population, and women's health is not a niche subcategory of medicine that's related to reproduction. It's much bigger than that. So, yeah, don't call them reproductive organs.

[00:05:56.400] - KAYLA BARNES-LENTZ

Good. Well, I'm glad. Now, I'm going to be bringing it down. Yeah, sorry.

[00:05:58.530] - JENNIFER GARRISON, PHD

That was really long.

[00:05:59.250] - KAYLA BARNES-LENTZ

No, I That is Todd answer.

[00:06:00.670] - JENNIFER GARRISON, PHD

You should interrupt me.

[00:06:02.340] - KAYLA BARNES-LENTZ

No, I love listening. Well, first of all, thank you to that donor because we're so grateful for them.

[00:06:08.370] - JENNIFER GARRISON, PHD

Yeah, that was the genesis of all the work that we are doing. In fact, that was the Bia ECHO Foundation. Since then, of course, we've had lots of other donors come in, and we're grateful to all of them. We rely on philanthropy, so we're not a company. We're not selling anything. But that was really the beginning of me, honestly, thinking about my own body. I was in my early 40s. To be honest, I had never really thought beyond practical things that I had to deal with on a monthly basis related to my menstrual cycle and vague biological ticking clock kinds of concerns that impacted most of the decisions I made as an adult. I had never really thought about how my ovaries work or what they do, which is really embarrassing, actually.

[00:07:05.130] - KAYLA BARNES-LENTZ

But it's really common. I think I'm an outlier really thinking about this because of the space I'm in. But no, it's such a good point. When we talk about ovarian aging, I'm very familiar with the 14 hallmarks of aging, right? What of those hallmarks or what is the process of ovarian aging?

[00:07:25.010] - JENNIFER GARRISON, PHD

Well, so here's the thing. Ovaries are no different than other tissues in that, what we know about them so far, and again, we don't understand everything about aging either, but the processes, the pathways, the molecules, the things that we know about aging in other tissues also hold true in ovaries. Things like MTOR signaling, NAD signaling, all of these things are really important and clearly play a role in ovarian aging. They're not different from your other tissues in that sense. What makes them very different, though, is that they're aging faster. What's happening in the rest of your body is accelerated in your ovaries by at least two fold. Ovaries are aging faster than the rest of the tissues in female bodies. That acceleration essentially sets up both an inequality, but also it means that at baseline, males and females are different in terms of their health span. Females live longer than males on average, but females have a shorter health span at baseline, and it is directly because of aging, this accelerated aging in your ovaries. Yeah.

[00:08:39.260] - KAYLA BARNES-LENTZ

Does that make sense? Yeah, it makes so much sense. Where are you at in the research? Why do we think, is it the brain then? Is it the brain telling the ovaries to age this two?

[00:08:49.350] - JENNIFER GARRISON, PHD

Let's be clear. First of all, I'm totally biased, so of course, I'm going to say yes. I think that that brain ovary axis of signaling is really the key. However, the answer is we don't know. For most things in women's health, we don't know the answer because we literally haven't collected the data or done the work. We have ignored female physiology for all of biomedical research history until very recently. We're coming from, I would say we're like a century behind where we need to be in terms of understanding. The answer to most questions is we have no idea. What we do know, the things we know are related to what happens when either ovaries stop working properly or when you take them away. Whether you remove them surgically or whether they go through this dramatic change in how they function either at and after menopause or in younger women who have primary ovarian insufficiency or failure. But I have historically been guilty of this, but I'm trying to change the narrative here. We have to stop bookending the conversation with fertility and menopause. Those are two really important aspects of ovarian function, no question. But that's not all they do.

[00:10:10.140] - JENNIFER GARRISON, PHD

Ovaries sit like your brain. Ovaries sit at the center of a complex signaling network, and they are talking to almost every tissue in your body. They're talking not just to your brain, but to your heart, to your bone, to your liver, to your skin. All of those axes of communication are different and complex, and I don't mean to trivialize them, and we don't understand them. But what we do know is what happens when ovaries aren't working or you take them away. And so nowadays, I try to call them the architects of health in female bodies. When you have function in ovaries when they're not working properly at any age. In a girl who's 10 or in a woman who's 85, that uncovers different health risks, different disorders, and different diseases, depending on who you are as individual. In that girl who's 10, if her ovaries aren't functioning properly, she might have issues going through puberty, or if she's gone through puberty, she might have irregular menstrual cycles or issues with her thyroid or crazy acne. That's all related to ovarian dysfunction. For a woman in her 20s, underlying ovarian dysfunction might uncover risk for things like polycystic ovarian syndrome, PCOS, or endometriosis, because even though that originates in the uterus, it's really about a conversation between uterus and ovaries.

[00:11:30.180] - JENNIFER GARRISON, PHD

Again, that we don't fully understand. Again, then for a woman in her 30s, we're totally familiar with the downstream consequences of ovarian dysfunction with respect to infertility, miscarriages. Then for a woman in her 40s, when ovarian function starts to fluctuate. It doesn't just go down in a nice stereotypical way that we see on that average curve. It's going like this at the level of an individual. That uncovers all of those 135 and counting symptoms that we associate with perimenopause. Then at and after menopause, it uncovers risk for cardiovascular disease, osteoporosis, autoimmune disorders, stroke, neurodegenerative disease, all those things that we talk about now. It's really about health. It's about maintaining health across female lifespan.

[00:12:22.020] - KAYLA BARNES-LENTZ

What do you think the possibilities are in terms of extending ovarian health? I've seen some interesting, I think, research on Rappamiacin, potentially extending the- We funded parts of that.

[00:12:35.910] - JENNIFER GARRISON, PHD

If I had to sum it up in one sentence, my goal, both with my own research in my lab at the Buck Institute, but also with the global consortium that we are in the center that we have is to try to understand how ovaries work, full stop.

[00:12:55.030] - KAYLA BARNES-LENTZ

What do we know now about?

[00:12:56.300] - JENNIFER GARRISON, PHD

Almost nothing. But in service of trying to to sync up aging and ovaries with aging in the rest of a woman's body as a way to extend female house span. The question of what's driving it, what are those underlying drivers? That's the trillion dollar question. Why is it so different between individuals? At an individual level, ovarian function is so stochastic. It's not just that graph that we see with the single inflection point in the cliff. That's on average. But at the level of the individual, lots of healthy young women go through periods of infertility and dysfunction that are unexplained. Lots of older women have periods of hyperfertility that are unexplained. There's just a lot that we don't get. But the goal, it's not to end menopause, which is a distraction from the real conversation because menopause is about menstruation, and we're not talking about extending periods forever. What we're talking about is maintaining that endocrine function of ovaries, the signaling network, all of that stuff, to maintain it for as long as possible to stave off all of those things that happen when ovaries aren't functioning properly. Does that make sense? Yeah. Where the research is, which is the question you asked, I would say we're at the very beginning.

[00:14:15.280] - JENNIFER GARRISON, PHD

To be quite frank, it's primitive. We're at the stage. We've been funding... The center is there to be the hub and the center of the universe with respect to this new scientific field that we're building, which is at the interface of longevity science, which you're very familiar with, and reproductive biology, which is a really mature field and has historically been focused around maternal fetal health and reproductive biology in the sense of fertility. Honestly, a lot of research has been around making more, bigger, better farm animals. Interesting. We're lucky that it started there with this Yeah, trying to make more bigger, better animals because that means that a lot of the early foundational work was done in these large mammals, like cows and sheep and horses, like these large mammals that have reproductive systems that are much closer to humans than, for example, like mice. In some ways, some of that early foundational research being done in large mammals means that we have better information than we might have if it had started the way that most biomedical research starts, which is in lower organisms. Not that those organisms don't have great... There's great questions you can ask there, but they're very specific.

[00:15:39.040] - JENNIFER GARRISON, PHD

Anyway, what we're trying to do is to make this new field, which we're calling reproductive aging, but again, I think we need another name for it. But it would be at the interface there and thinking about how aging, specifically for females in female reproductive organs, really influences aging in the rest of the body.

[00:15:59.240] - KAYLA BARNES-LENTZ

You're looking If I read correctly, you're looking at younger women with rapidly declining ovarian health, to get an understanding of maybe what's happening with them, to them, understanding what's happening on the big picture.

[00:16:13.820] - JENNIFER GARRISON, PHD

Well, we're funding research Search. We fund grants to scientists all over the world. The reason we are where we are, they're obvious now, but societal taboos around talking about female bodies, which I think are largely being shattered. That's That's a fun thing. But then there's this data desert. There's a gap in data that we've been talking about that's just profound. That is directly because there has been no funding, no funding on the governmental research funding side. That's really what drives investment as well. There's been very little funding on both sides. We're trying to fill that gap until the NIH, it's a big ship to move. Until they step in and really take over, we're funding grants to scientists. For example, that study you cited, which is happening at Columbia University, one of our grantees, Yushin Sa, partnered with a doctor there to set up what turns out to be the very first clinical study in women, where the endpoints they're measuring are not for fertility, they're for ovarian aging. It doesn't really matter what the results are. They're still in the middle of that study and everything's blinded, so there are no actual results. But even if that study, even if that molecule fails, it's a landmark study because it plants a flag, and it's the first of what I hope will be many clinical trials for interventions that would change over in aging.

[00:17:49.860] - JENNIFER GARRISON, PHD

That's really exciting. But that's just one of... We funded 49 scientists so far all over the world, and there are so many discoveries that have come in the last four years. The pace of discovery is much faster and much better than I could have ever hoped for. We're really at this inflection point that I think is both exciting and also like, thank fucking God. I know. We need this.

[00:18:13.650] - KAYLA BARNES-LENTZ

It's a wild That we're talking about the first ever.

[00:18:17.270] - JENNIFER GARRISON, PHD

Oh, you can't even... Oh, my God. We funded grants. We funded grants very broadly because we don't know what we don't know, and we don't even know where to look for those driving factors. It could be one thing that happens during development. It could be one thing that happens during puberty. It could be five things that happen at different time points. We have literally no idea. We funded a lot of really broad research. Some of the things we funded four years ago were the first OMIC studies, the first single cell sequencing or things like that in ovaries, both in mice and in humans across ages. We literally, just a few months ago, and from that initial work, tons of other people have come into the field, which is so great. But from that initial work, we had to have a meeting about three months ago where we brought together, I think, more than 60 different scientists from all over the world who now have been doing large-scale omic studies, whether single-cell or a single-cell with spatial data. We had to get together for four days in a room because right now, it's very difficult to impossible to compare across them.

[00:19:29.970] - JENNIFER GARRISON, PHD

Because we've never actually decided as a field what to call a cell type in an ovary. That's where we are. Can you imagine saying that about your heart? Oh my gosh. Or your liver? No. No. We did for over four days, and this was for The Copian tubes for uterus and for ovary. It was wonderful. It was sponsored by the Chan Zuckerberg Initiative because they have these large-scale tissue databases for researchers where they for human and for mouse and across aging. They're amazing. They didn't have reproductive organs for females for a long time. They're doing that now, but they sponsored it. We sat down for four days, and now we have a framework within which we can compare across data sets because we named some of the cell types in the ovary. We have an ontology for what to call cells in the ovary. I'm so excited. Can you share what that was so we all know? I mean, yeah, it's not simple. Ovaries are pretty complicated. In the In the grand scheme of things, they're like a microcosm that reflects female physiology, right? We're complex. We have to treat-In all ways we're complex. In all ways.

[00:20:38.540] - JENNIFER GARRISON, PHD

Female physiology is the most beautiful and complex thing in all of human health, and that's also true for ovaries. If you think about it, there's so many different things happening. It's not like your liver, where if you were to slice through it, it's pretty homogenous. You can pretty much tell what's what. There's a couple of different cell types, and they all They have very prescribed functions. But the ovary, I think of it as a ball of balls, so all different size balls. But then if you think about the trajectory of going from the most primitive primordial follicle, which is the thing that's just sitting there for decades, waiting, waiting, waiting. Once it gets recruited to grow, every month you have a thousand of those that are recruited to grow during your cycle. Once it gets recruited to grow, it takes about a little over a year to go from the point of being a quiescent primordial follicle to something that could be ovulated. There's that time scale. Why? It's changing across a year. But then there's also the time scale of 28, which is a total myth, but whenever your cycle is, 30-ish days or 26 to 30 days.

[00:21:58.810] - JENNIFER GARRISON, PHD

There's also that time scale where things are going through. That's the tail end of this developmental window. But each month, a thousand primordial follicles get recruited to grow. Every month, and so you can imagine, if you think about what that means in your ovaries at any given time, there's just so much dynamic stuff happening, like this macroscopic remodeling at the level of the tissue. Then there's also at the microscopic level, at the cellular level, the cells that... The egg is the egg, But the cells that surround it in the follicle, the ones that are closest to it, are called granulosa cells. A granulosa cell in a less developed follicle will go through the same cell will change identity. It changes shape, it changes what hormones it makes. It changes everything it does across both of these traject. There's so many different changes in cell states, and it's beautiful, but also a little complicated. Yeah. We're just now mapping out what the ovary looks like. Wow.

[00:23:07.170] - KAYLA BARNES-LENTZ

Okay. All right. Well, that's where we're at.

[00:23:09.540] - KAYLA BARNES-LENTZ

Hi. We're taking a short break from the podcast to discuss a new community that I have launched. I want to preface this by saying that I will continue to post content on my social platforms and conduct interviews on this podcast that are both free and applicable to both sexes. But as a woman, I have unique insights and perspectives on female health. I recently I finally launched my first ever paid offering, and this is a female-only health optimization and longevity community. If you are a male, you can skip this portion of the podcast or you can forward this information to a female that you think would be interested. I set out to create the most valuable longevity optimization community for women. I have spent over the last decade dedicating my life to human optimization and have dived deep into the female-specific optimization and protocols. This is a place I want learn everything you need to know about optimizing your health, longevity, and mindset. I made this a community only for women because I wanted us to be able to be open, which I didn't feel could be done in the comment section of my Instagram. I also love the idea of women sharing protocols of what's working best, and everybody within the community can offer valuable insights to each other and support.

[00:24:23.070] - KAYLA BARNES-LENTZ

Members get weekly and bi weekly Ask Me Any Things, exclusive content and protocols like articles videos, and a whole host of courses. You'll receive up to date, Female Longevity is Science. You'll also get community in connection with like-minded women, access to virtual and in-person events with me, and your membership will help support female human studies in the very near future. You can learn more about this membership on my website, KaylaBarns. Com.

[00:24:54.790] - KAYLA BARNES-LENTZ

If we think about what do you feel is potentially the most promising? If we look at It's a case of rapamycin, right? It's an immunosuppressant, and what do you think the mechanism could potentially be there?

[00:25:06.700] - JENNIFER GARRISON, PHD

Who knows? Certainly, a very reasonable hypothesis would be that it's an immunosuppressant at high doses It's an immunosuppressant. At low doses, which is what we're talking about, it probably has some anti-inflammatory properties. Obviously, inflammation with age is a real problem, and it's a hallmark of aging. But who knows? At low doses, it's not so clear what it's doing necessarily. There's so many things like that. I mean, it's the norm, not the rule, that we typically don't know how drugs work. To know the mechanism with some certainty is like, that's not the minority of things. The vast majority of things that we use as drugs, we don't understand how they work. Take the GLP-1s, for example. We know what GLP-1 does normally in physiology, it's a neuropeptide. It's important for satiety, but the GLP-1 drugs mimic levels of the hormone that are 10,000 times what you would normally find in your body. So who knows what the mechanisms are that are happening there? We don't know.

[00:26:16.210] - KAYLA BARNES-LENTZ

Interesting. Well, I can't wait to find out. I know.

[00:26:18.920] - JENNIFER GARRISON, PHD

This is the thing. We don't have enough time to go through all the 49 different grants that we've given away and then also walk through all the things happening in the center that are exciting. But suffice it to say there's a lot of cool stuff happening. I think we're still at the stage where the lowest hanging fruit and the things that are going to be available to women in the next one to five years are going to be biomarkers, diagnostics, products. Those are super important. I call those bandaid solutions because they're not truly moving the needle in terms therapeutics or interventions. But those will come. But the science that we're doing right now is absolutely essential and really generating the IP to fill that drug pipeline because it's empty right now. We don't have any drugs that are anywhere near ready for prime time for this, but it's coming.

[00:27:23.710] - KAYLA BARNES-LENTZ

I'm excited. When it comes to, are there any biomarkers that you can look at now that's going to... We Yeah, I know. Amh for maybe the amount of follicles or eggs you might have, but is there anything you can look at to understand your ovaries?

[00:27:37.000] - JENNIFER GARRISON, PHD

Amh will tell you about the follicles that are developing, right? How many follicles are developing. That's great for fertility. There's a handful of other things that we understand with some precision, but we're frustratingly not there yet in terms of having what we should have had for the last 50 years, which is a women's health diagnostic panel. You should be able to go to your doctor for your physical or your pop smear and have a panel of biomarkers that will tell you, number one, where are you in that trajectory? Until we can extend endocrine function of ovaries, you should at least be able to know where you are because it's so variable between individuals. It's not like you can look at your watch and say, Well, I'm 32. On average, I'm this many years from menopause, but at an individual level, you might be 14 years off of that curve. Those kinds of things are coming, but we don't have them yet. It truly is because we haven't collected the data.

[00:28:42.540] - KAYLA BARNES-LENTZ

Where are we at? The Omex I'm very familiar with TruDiagnostics, who is doing a lot of the biological age testing. I did see that they rolled out, I think, some organ testing. I'm not sure how accurate it is at this point. Are we going to have something like that for ovaries?

[00:28:56.670] - JENNIFER GARRISON, PHD

That's the hope, right? That's the hope and the promise. I think for all of those biological age tests, they're incredibly useful research tools. I think that I'm of the opinion that using them in humans is really premature right now because we don't know what they mean. The question is, I think we've answered the question, can you measure biochemical or cellular features that tell you something about the rate of aging? I think the answer is yes. There's lots of different things that we've measured that we think might tell us something about the rate of aging. But what it's telling us and what it means for all of these tests is we don't know yet. That's why I think it's premature to give them to people because at the end of the day, it's a lot. It's expensive, and we don't really have a good handle on what it means. That's not to say that in six months, there won't be a landmark study that really gives us a handle on that. But it's because it's hard to do these experiments in humans. What you really need is longitudinal data, and we don't have that time. So the question is, how much large scale data can we collect across all of these different markers that we think are measuring rates of aging in different ways and then make sense out of it?

[00:30:24.790] - JENNIFER GARRISON, PHD

There's a lot of hope, but I do think it's a little premature to sell people that they can know something about their biological age. The reason I say that is because, I mean, I'm sure you've done this yourself. You're one of the most tested people on the planet, so maybe you should be talking about this, but you can take the same test at different times of the day or across different days and get completely different results.

[00:30:49.940] - KAYLA BARNES-LENTZ

I like the data, but I'm also really heavily leaning on those tried and true, like grip strength and gait speed. How easily can you get out of a chair You're not touching something when you're older? I'm excited for it all. I do pretty much all the tests just to see what happens. Of course. That's all you can do at this point.

[00:31:08.710] - JENNIFER GARRISON, PHD

For women, they ask me people. I'm not a medical doctor. I'm a PhD scientist, so I don't give medical advice, but I can tell you what the data says, and I can also tell you what I do. I think at this stage, the best and most powerful thing that women can do is to arm themselves with information about their own physiology. Especially young women, I think part of those societal taboos that have been shattered, one that still lingers is around menstruation and menstrual cycles. Certainly, I would have never talked about my menstrual cycle publicly when I was younger, and I thought of it as a nuisance and just something that I had to deal with and get through. I just assumed that I was going to have some underlying dysfunction, pain, or bloating, or dramatic mood swings I just took that as part of what I had to suck it up and deal with. But I think that we can project a different message now to younger women, and that is that your cycle and understanding, like really at high resolution, exactly what your cycle looks like, you should think of that as a superpower.

[00:32:19.170] - JENNIFER GARRISON, PHD

I agree. You can harness that. If you really understand how your body works, you can take advantage of every single one of those highs and lows. Oh, yeah.

[00:32:27.740] - KAYLA BARNES-LENTZ

I do.

[00:32:28.310] - JENNIFER GARRISON, PHD

Yeah. I do. That's the message I think we should be broadcasting now is you have a superpower, and you should just learn how to use it.

[00:32:36.130] - KAYLA BARNES-LENTZ

I love that. I'm norvég in the next quiz here. The Natural Cycles app. I learned so much. Then I even program my workouts around your peak strength, ovulation.

[00:32:47.830] - JENNIFER GARRISON, PHD

Yeah, athletes have been doing this for a long time.

[00:32:49.260] - KAYLA BARNES-LENTZ

Right. I love it. Well, super exciting. I can't wait to get more info. If women are wondering how can they, if possible, I know we still need a lot of data, but extend any ovarian reserves, ovarian health. What was your recommendation be?

[00:33:06.310] - JENNIFER GARRISON, PHD

At this point, what we can say is that, like I said, all of the pathways that we know about that function in the rest of your body are also functioning your ovaries. It's just accelerating. And so anything that impacts aging in your other tissues is going to impact your ovaries. That means that diet and exercise are by far... Thinking about how you move your body and what you put into it are by far the biggest levers that we have to pull. And I wish I had something more satisfying to say, but that really is the truth. I do think that with respect to ovarian function, certainly sleep is one of the biggest things that impacts your physiology. Again, just arming yourself with information, knowing for the things we can measure, exactly what your normals are so that if anything moves off of normal, you can spot it immediately. You can have that knowledge and that certainty that it is different than it should be. Hopefully, that will give women more agency and more confidence to go to their doctors because a lot of times, because we don't know what we don't know, I think physicians are very…

[00:34:23.420] - JENNIFER GARRISON, PHD

They tend to be really conservative. If a doctor tells you, Well, don't worry about that. It's normal to move around. Of course. Most women will be put back on their heels and be like, Okay, well, whatever, and then not get the care that they need. I think if you really know what's normal and you see it move and you have that certainty that there's something different that you can push back a little bit better.

[00:34:53.730] - KAYLA BARNES-LENTZ

What do you think about early intervention of HRT in a perimenopause state? Could that potentially extend?

[00:35:00.790] - JENNIFER GARRISON, PHD

Again, we need more data, but there's, I think, a lot of promising preliminary data to suggest that that's the case. I don't call it HRT anymore. What do you call it? Well, because if you say replacement, hormone replacement therapy is- Yeah, for the end of the case, they're gone. Well, I would say that for women who are in their 20s who have primary ovarian failure, which means that they go into menopause overnight for reasons we don't understand. It's right. You think it's so sad. And the medical community treats it like a medical emergency and really throws the kitchen sink at it. When exactly the same process happens 20, 25 years later, we call it normal and tell women to suck it up.

[00:35:44.200] - KAYLA BARNES-LENTZ

There's also a That's so sad.

[00:35:45.760] - JENNIFER GARRISON, PHD

There's a cognitive dissonance there that's mind-blowing because it's the same process anyway. But it's a tragedy and a medical emergency when you're 20, but when you're 45 or 49 or 52, it's just Suck it up. Sorry, but I want to answer your question because I can really move around, and I don't mean to. I just call it hormone therapy or menopause hormone therapy because replacement makes it sound like there's something wrong with women add in after menopause? Why not? Ovaries are still doing something after menopause. I think most women don't realize that. Again, we only know what happens when you take them away. But in postmenopausal women who have their ovaries removed versus who keep their ovaries, the women who have their ovaries removed have poor health outcomes. There is still something happening there. It's just very different from what they were doing before. But the question of whether trying... To be clear, hormone therapy is an amazing bandaid. It's the best bandaid we have to treat all of those health conditions that are related to hairy and postmenopause. But it's primitive. It hasn't really changed. There's There's been no innovation except for the introduction of the estradiol patch, patch versus oral.

[00:37:06.530] - JENNIFER GARRISON, PHD

There's been no innovation since it was introduced. Part of that has to do with all of the misinformation around the PHI study. But I think there's a lot of opportunity for innovation there. While it's a bandaid, we can make it a lot better. But I do think that there's certainly a lot of evidence that making sure you maintain those two hormone levels is beneficial. If you can start it sooner, then... That's a conversation with the doctor.

[00:37:44.380] - KAYLA BARNES-LENTZ

Yeah. Absolutely. I've read that if you have children after the age of 30, you have, I can't remember the exact stats, but an exponential increase in potential lifespan. Same thing if you have children over 40, have Have you read about this at all?

[00:38:02.140] - JENNIFER GARRISON, PHD

Well, so there's a lot of studies like that. Really, you can think about the age at which you're having a child as a proxy for age at menopause. Age at natural menopause is really just the day on which you haven't had a period for 12 months. But obviously, you can't have children if you're not cycling. There's a correlation, and we don't understand causation, but there's a strong correlation between going through menopause later on average and living longer. There's a positive correlation between women who go through menopause later tend to live longer. But it's important to say that that's a statistical average across a large data set. At the level of the individual, again, everything's stochastic. It doesn't mean that if you go through menopause early, you're going to die young. But that correlation is really interesting because it extends to male brothers. There's an underlying genetic component of age and natural menopause that's shared between sexes that's important for longevity. Understanding ovarian function is important for more than just women. I love that. Again, the age at which you have your last child is a correlate for your ovarian function and for your age at natural menopause.

[00:39:23.230] - JENNIFER GARRISON, PHD

All of those things are true.

[00:39:25.490] - KAYLA BARNES-LENTZ

Got it. Do we... You know how we have the blue zones and the longest lived people, and we're going to follow them around and do some research. Do we have the age of the woman in the latest menopause, or are we able to research?

[00:39:39.220] - JENNIFER GARRISON, PHD

This is an interesting question. When we first started working in this space many years ago, and I started giving talks about this, I got so many emails, and I had so many women coming up to me after I gave my talk saying, You should study me because I'm 56 or I'm 58, and I'm still cycling. I was like, Oh, cool. At first I was like, Oh, yeah, totally. Then I started collecting these stories and collecting this information, and I realized that sometimes women think they're cycling and they're not. But also, again, it comes down to this, we don't understand the interindividual variability. I actually don't think it's unusual. I actually think that there's just this huge range. To be called normal, age in natural menopause can span 14 years. So 51.7 right now is the average, don't quote me, it's something like that, is the average age. But it's a velleyshape curve, and there's lots of people out here, and there's lots of people out here. Again, we don't understand why it's so variable at the level of the individual. But if we did understand that, that would give us a clue about what those underlying drivers are and push us towards having the knowledge that we need to do these interventions.

[00:41:02.400] - JENNIFER GARRISON, PHD

It's all very tantalizing and exciting. But I actually don't think... I also used to have women telling me that they had miracle babies. I'm like, Oh, I had a baby when I was 50. I had a baby when I was 49, naturally. I'm like, That's not a miracle. That's your biology. It's just that's how little we understand ovarian function, quite frankly.

[00:41:28.520] - KAYLA BARNES-LENTZ

Are there any... You You do a genetics test, right? You can either detox better or worse, and you might have the MTHFR. Are there any gene correlations with any of this?

[00:41:38.130] - JENNIFER GARRISON, PHD

Yeah, there's been some really... So age and natural menopause is... It slips a little back and forth, but something like 20% of that is determined by your genetics. There have been several landmark studies published in the last few years, mostly out of labs in the UK, some in the US, around what contributes to that, at least from a genetic standpoint. One of our grantees, actually, what she published was that something like more than 90% of the hits that they got, so it's a GWAS study, a Genomide Association study. They find places in the genome where above a statistical threshold, this loci, this part of your DNA is totally... What's here totally determines, helps determine age of natural menopause, right? Almost all of those spots were outside of coding regions. Normally, we think about when you do gene association studies, you're looking for genes. You're looking for hits that are inside of protein coding regions, genes. These are all outside of genes. Most of the hits fall in these regulatory regions. It's much harder to find specific genes that are... Because these regulatory regions can influence lots of different things nearby, but they can also influence things that are really far away, and it's a much harder problem to solve.

[00:43:19.520] - JENNIFER GARRISON, PHD

It's interesting. Yeah. It's cool and interesting, and there's a lot of landmark studies, but it's not like they could say It's like, Oh, it's APOE. All these mutations in APOE are associated with older age of menopause or earlier age of menopause. No, no. All the hits that they find, most of them are outside of the genes. They're in these regulatory genes that can influence all kinds of things.

[00:43:47.860] - KAYLA BARNES-LENTZ

Would that be in the apogenome?

[00:43:50.840] - JENNIFER GARRISON, PHD

Well, there's things like that, too. But no, we're talking about coding changes at the DNA level, but not inside of genes. Because most of your genome is actually not made up of genes. It's made up of all this regulatory stuff, which turns out to be important, unfortunately, and trickier to study.

[00:44:07.660] - KAYLA BARNES-LENTZ

Absolutely. I've heard before that there is essentially you can do a telomere test of an ovary. Is this, do you know anything about this?

[00:44:16.490] - JENNIFER GARRISON, PHD

I mean, telomeres are just... You know what a telomere is? Yes. Yeah. So telomeres are just these pieces of DNA that get shorter every time your genome is replicated inside of a cell. There's a lot of controversy around whether your telomere length is related to hallmarks of aging. Early studies said, yes, telomere shortening is one of the things that drives aging, but there are more recent studies showing that actually it has nothing to do with aging. This isn't my area of expertise, so I'm not going to make a call there, but every cell in your body has telomeres. Then It's always different.

[00:45:00.460] - KAYLA BARNES-LENTZ

I'm the one in the old... I'm throwing out different ideas. It's like, we need to know this.

[00:45:06.360] - JENNIFER GARRISON, PHD

Yeah, I think... Honestly, I think, again, for me, it comes down to... I think that there's lots of tantalizing data, especially in animals, but also in humans, that what's going to be important is actually not the egg itself or even the follicle necessarily around the egg, but that the somatic tissue, the rest of the ovary, the nest, so to speak, the rest of that tissue is what's going to be important for finding, discovering the things that we want to discover.

[00:45:43.700] - KAYLA BARNES-LENTZ

That's where we're really focused. I guess. I agree. So, okay, how do we get more funding to this cause? Because we were thinking about it. My friend who was with me last night, we were trying to break it down. Okay, if I have 400,000 1,000 followers on Instagram and they all donated $5. That would make a huge difference. We did this with a lot of... I knew a lot of other women in the space, as I'm sure you do. How did we make that happen? How much would make a big impact?

[00:46:14.360] - JENNIFER GARRISON, PHD

We're at the stage now where we're about to do a large philanthropic fundraise in service of raising enough money to continue giving away the grants. Because we've only given away $14.5 million so to 49 scientists all over the world. We have now this track record, and you can see we're reworking our website right now because we changed our name. We used to have this long name, and the word reproductive was in there. I can't tell people to stop calling them reproductive organs. I don't have that in our name. We're changing our name to productivehealth. Org. Get it? Reproductive with a R-Cross out. I love that. Reworking our website. As soon as that's done, I'm going on a huge fundraising, I mean, tear, because I think we should have a lot more funding behind this. When we give away our grants, we've done two cycles. Each time, our funding rate was less than 8% management, meaning that there were hundreds of applications that we had that were great, that were meritorious, that we would have funded if we had more money. That's number one, we just need more money to fund more grants to push this forward.

[00:47:30.340] - JENNIFER GARRISON, PHD

But second, having been in biomedical research for 30 years and running my own lab and also applying for grants my entire career, science funding is broken. I mean, it's fundamentally broken. As a researcher, I have a research lab. I have to fund every salary, so the salary is for myself and everyone who works for me, all my PhD students, my postdoctoral fellows, my technicians, everyone in my lab, I fund their salary, their benefits. I fund all of the equipment, all of the supplies, everything. I have to raise the money for that. That's why I apply for grants from the government, from private foundations. Governmental grants tend to be for a very specific project. An NIH grant that I get, it might be somewhere between three and five years long for different amounts of money. None of that enough to run my whole lap. What you end up with is this patchwork of grants that are for different amounts of money, different lengths of time, and they might be for a very specific project. But then when that project ends, you have to apply for another grant, and so the science might shift. The other thing about especially governmental grants is that they tend to reward very incremental science.

[00:48:55.670] - JENNIFER GARRISON, PHD

It's basically the incentive structure that we have for science funding is completely misaligned with what we want scientists to do, which is to ask like moonshot questions, to think about paradigm shifting experiments, to really be creative. You can't do that if you're constantly trying to fit into a box with a grant that is for a specific project. There's only one funding model in science that I know that works, and it's called HHMI. We don't need to delve into it, but at the end of the day, people who are lucky enough to get HHMI funding, they fund the scientist in the lab, not a specific project. They give them enough money and a runway of seven to nine years to do real work. They give them the freedom to do whatever they want. You know the most about your science. You are the expert. You go do whatever you want to do. Be creative, take risks. If you look at, it's called HHMI, it's the Howard Hughes Medical Institute. It was from the estate of Howard Hughes is where this all came from. But if you look at HHMI investigators over their history, they're way overrepresented in Nobel Prize winners, in science that you've heard of.

[00:50:14.640] - JENNIFER GARRISON, PHD

If you think about in the last five years, what scientific discoveries or what things do you know about CRISPR? That was an HHMI investigator. Nobel Prize winners, most of them have had or are HHMI investigators. We can't be HHMI. They have a budget of $600 million a year. But what we can do is think about with these grants, how do we make it so that if someone's doing something that we think is worth continuing, because we're giving away at this point two-year grants. What I don't want to have happen is for those projects at the end of two years for them to die or for them to have to pivot and do something else to get some other grant. We want to have a second pot of money that is specifically for sustainable funding so that existing grantees or former grantees or center members can apply to that and keep doing what they're doing. Does that make sense?

[00:51:06.760] - KAYLA BARNES-LENTZ

Yeah. But what about this, I mean, crowd-sourcing idea? Half of the population are women. They have a lot of power. We want to invest in things that are four-way in buy with them.

[00:51:17.640] - JENNIFER GARRISON, PHD

Five dollars from 100 million people will do a lot. Right.

[00:51:22.470] - KAYLA BARNES-LENTZ

I mean, let's talk offline about how we- I have a lot of ideas.

[00:51:25.270] - JENNIFER GARRISON, PHD

We have a lot of... It has to be done in the spring, I think, but we're thinking about doing a social media campaign that would be like the Ice Bucket Challenge. The Ice Bucket Challenge raised $100 million for ALS research in six weeks. Most of the people who did it didn't donate money at all. The people who did, most of them donated $5 or So it would be the egg toss challenge.

[00:51:49.600] - KAYLA BARNES-LENTZ

I love it. I love it. I want to be.

[00:51:52.670] - JENNIFER GARRISON, PHD

Lots of ideas like that. I also think we're approaching companies, particularly I really like large luxury skincare that focuses on women and particularly focus on aging in women, companies like that. But also any companies that have products designed for women to ask them whether they would be willing to put a passive donation field in their checkout. Do you want to donate to research for women's health, a dollar or three dollars, but just a passive thing at the checkout to ask if they would willing to do that.

[00:52:31.300] - KAYLA BARNES-LENTZ

I know things like that. A lot of female brands and some great people actually that we'll talk with.

[00:52:36.980] - JENNIFER GARRISON, PHD

But this has been such a pleasure. Thank you so much. This was very fun. I know.

[00:52:40.110] - KAYLA BARNES-LENTZ

It feels nice to get down for so long.

[00:52:42.630] - JENNIFER GARRISON, PHD

I know. I can go on and on.

[00:52:44.470] - KAYLA BARNES-LENTZ

I love it. No, thank you so much for being here. Thank you.

[00:52:47.400] - KAYLA BARNES-LENTZ

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