Female Reproductive Longevity & Fertility with Dr. Jennifer Garrison - Podcast

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Welcome to another episode of the Longevity and Lifestyle Podcast. I'm your host, Claudia von Boeselager, here to uncover the groundbreaking strategies, tools, and practices from the world's pioneering experts to help you live at your best and reach your highest potential. If you haven't done so already, please subscribe to the podcast and share with those you love. My guest today is none other than Dr. Jennifer Garrison. Jennifer is a world-renowned scientist who has won numerous awards for her research on aging and brain science. She is the faculty director of the Global Consortium for Reproductive Longevity and Equality and an assistant professor at the Buck Institute for Research on Aging, and also holds appointments at the University of California, San Francisco, and the University of Southern California. Welcome, Jennifer, to the Longevity and Lifestyle Podcast.

Thank you so much for having me, Claudia von Boeselager.

Jennifer, I'd love to start with a quote and also to set the stage a little bit for our exciting conversation that I've been looking forward to for a very long time. So you said that studies show women who have later menopause tend to live longer and have an enhanced ability to repair their DNA. But women with natural menopause before the age of 40 are twice as likely to die early compared with women going through natural menopause between the ages of 50 and 54. So I'd love to kick off just digging into female aging, fertility, and reproductive aging specifically. Can you expand a little bit why this is your area of specialty, and what is it that women need to know about this area.

Absolutely. That's quite a, that's quite a quote to kick off with. To be clear, that's not my work. That is the results of several studies that were looking at correlations between reproductive span. So that's the age at which a woman goes through menopause and her overall lifespan. Now, I would say that those are average numbers. And so I always want to back that up by, by telling women that even if you go through an early menopause, that doesn't necessarily mean that you're doomed to live a short life. In general, female reproductive biology is really incredibly distinct and stochastic and variable at the level of the individual. So what we're talking about here are averages, just to— of course, to be clear. I work on— I am a neuroscientist, but I work on understanding how the brain communicates with the rest of the body and how that changes during aging. And that led us to reproductive aging, thinking about how the brain talks to ovaries and the uterus and other reproductive organs. And the reason I, I, I find this area of science so compelling is because we don't know that much about it. So this is an area of biology that has really been long neglected. And if you don't know anything about ovaries, and to be honest, I didn't know that much about ovarian function until 5-ish years ago, even though I happen to own a pair. If you don't know that much about ovaries, they're fascinating.

Share with the audience why they're so important above and beyond just pure reproduction.

Yeah, there's so much to understand about them. The first thing to know is that they're incredibly complex, right? Unlike any other organ in the body, they go through this like dramatic dynamic remodeling every single month during adulthood. Every single cycle that a woman goes through, there's this huge macroscopic dynamic remodeling of the tissue that happens. And so they're incredibly dynamic, but they're also the first system in the body to age. So ovaries are essentially aging at something like 2.5 times the rate of other tissues. And what that What that means in practice is that a woman's ovaries are already showing overt signs of aging in late 20s, early 30s, which is when most of the other organs in a woman's body are functioning perfectly, almost at peak performance. And so that comes as a shock to a lot of women. And we, we think that if we can understand why ovaries are aging prematurely, that will have direct implications on understanding aging in the rest of the body. There's, there's misconception, I think, that, that women somehow have the ability to rejuvenate their ovaries or extend their fertility by preserving eggs, by taking reproductive hormonal birth control. And that's just not true. So women are born with all the eggs they're ever going to have. Somewhere around 26 weeks of gestation, a female human has about 6 or 7 million eggs in her ovary. By the time she's born, that number drops to about a million. By the time she goes through puberty, that number is somewhere between 300,000 and 400,000. And then once she starts cycling, every single month that she ovulates, she's going to lose about 1,000 eggs every single month. And so those numbers drop. And it's not just the numbers, but also the quality of the eggs changes and goes down with age during adulthood until somewhere in her 40s or 50s, she will essentially run out of eggs and her ovaries will stop working and she will go through menopause. And menopause is a funny thing. It's a single day. We often, when we're talking about menopausal symptoms, we're talking about either perimenopause, so before menopause, or postmenopause, after menopause. Menopause itself is just the day on which a woman has not been, has not had a period for 12 months. So it's just a single day in time. Ovaries are doing a lot of things that are important for health. I think most women are pretty familiar with the consequences of ovarian aging on fertility. Not as many women are familiar with the consequences of ovarian aging on overall health. So ovaries are also secreting a whole cocktail of different chemicals and hormones that are important for general health.

Yeah, I'd love to dig into a few things. And when we were talking about egg freezing as well, and I had some questions from the audience in advance of our conversation asking like, what is the ideal age and when is it too late to look at egg freezing? Was one as well. So maybe we could just look at egg freezing as a topic.

Sure. And I should just Total disclaimer, I am a PhD scientist. I'm not a medical doctor. And so I am not giving any kind of medical advice. So everything that I'm telling you is either science-based or it's just my opinion. And egg freezing is a really controversial topic in my opinion. I think there's been something like, I don't know, IVF has been marketed as a talisman for all reproductive aging issues in women. I think it's really over-marketed and I think, you know, it's an amazing procedure. It's incredible that we can do this, but it's definitely not a panacea in terms of a solution. It's a Band-Aid. And a lot of women, I think, today are sold this false narrative that if they freeze their eggs, they're going to have this insurance policy and they don't need to worry about their fertility because at some point they'll be able to thaw those eggs and have a baby. And while that's true in some cases, We don't really very well on the science side understand how to freeze eggs. We do it and we have some success, but I think the numbers are something like you need to freeze 15 or so eggs to get one that works on the other side. And so those aren't very good statistics. That kind of speaks to our inability or our lack of knowledge around really what makes a good egg. And I think egg freezing is a good option for some women and not a good option for others, and there are a lot of risks associated with it. You're basically hyperstimulating your ovaries to produce a lot more follicles than they normally would. We don't truly understand what the consequences of that hyperstimulation are on a woman's body, certainly not long-term. And then it's an invasive procedure. It's not just like getting a shot, it's actually an invasive procedure, and there are risks associated with it. Having said all of that, I think that there are guidelines about the ages ages at which a woman can and should freeze her eggs. The older a woman is, the fewer quality eggs she'll get. And yeah, I think it's a really, it's a really fraught issue because I think IVF came out of cancer research, not reproductive aging research. And I would love— part of what we're trying to do is to fund scientific research in this space so that we can get rid of the need for IVF. That would be my moonshot goal, is to just get rid of the need for it, but please, I would love to discuss further, especially I'd love to hear your questions and thoughts around it.

Yeah, no, I think it's so helpful. And I do have a lot of audience members and I think people see the trends that there are a lot of companies that are now even supporting, or a bunch of companies supporting female employees to do the egg freezing. And I think that the point you made is so valid that it's not the be-all and end-all, right? It's not. You're 100% guaranteed to have 100% success if you do the egg freezing. And I think it's such an important awareness that people have as well. And at the same time, your overall health will play a huge role in that as well. So you can't freeze your eggs and then completely destroy yourself and your health and be partying all the time and not sleeping or whatever it is as well, and expect in 10 years' time to be completely in a great state to get pregnant and to have children as well. So I think there's almost that misconception that, as you were alluding to as well, that it's 100% guarantee if you freeze your eggs, you're fine. So I I think that's important. And there were some questions around what is an ideal age. Obviously people say the younger the better, right? But just that understanding of the whole health consensus around it also.

It's so true. It's so true. Yeah, I really, I call it the anthem of IVF and it's really misleading. And I think one of the things we're trying to do is just to change that narrative, to just let women know that, that yes, this is an option, but it's a pretty serious procedure and you really don't have any guarantees on the other end. Certainly I think the statistics are better if you freeze embryos, but But it's the same thing. I was— and women come to me all the time and they say, I had 30 eggs frozen and guess what? I thawed them and nothing came of that. And now I'm approaching 40 and I don't have any other options for biological children. And that can be really devastating. I think it's important that we educate women. And what you said about other factors is so right. The eggs in our ovaries, they're certainly undergoing some kind of a decline with age, but for the most part, they're quiescent. They're not doing very much, but the environment of around the eggs, right? Both the microenvironment inside the ovaries, but also the macroenvironment of the woman's whole body and how it functions, how the system functions. That really does have a dramatic impact on, on, on egg quality and also on a woman's ability to get pregnant.

Yeah. And I think one huge thing is obviously stress levels, right? And I know especially people working in tech or in, say, banking, finance, high-stress environments— not to say in other areas it's not as high stress, but I guess obviously an individual ability to deal with stress also, but I used to take stress that seriously. I could cope on little sleep. It was okay. My foolish twenties, just think I'll be fine until it starts catching up with you. And I think that for people and a lot of my, my people reaching out that were interested in with questions from my audience to think of it as a tool, but the environment around it is just as important as well. Jennifer, I'd love to ask you, like, what are some supplements, or what are some things that you are seeing in your research and research you have been looking at that are very supportive of increasing the longevity, if you will, of fertility for women?

I wish that I had some suggestion or recommendation for a magic pill. Honestly, the things that I've seen and the things that I do myself that are most beneficial are the same things that are beneficial for aging in general, right? The same pathways and mechanisms that we know about so far that control aging in the rest of the body, those things are also operating in the ovaries. And so it makes sense that things like diet and exercise are actually probably the best and most comprehensive interventions that someone can apply. I think that's not to say that we won't discover things that, that, that will become treatments. And I have a lot of hope that in the next few years that the research will yield targets and pathways that we can think about for therapeutics that would basically improve the quality of women's fertility and hopefully extend reproductive span so that we can, we can let women have a little bit more flexibility and choice in when they decide to start a family, if they want to start a family, and so that we can preserve those hormones, those, that cocktail of chemicals that are so important for general health. I think there's a lot of conflicting evidence about supplements and nutraceuticals and things like that. And so I personally, beyond making sure that I get all of my daily vitamins, and for me sometimes that means supplementing vitamin D because I certainly don't get enough direct sun. I'm melanin challenged. And so I wear a lot of sunscreen, which means that even when I go out in the sun, I'm probably not making vitamin D. So that for me is important. I monitor my vitamin D levels with my doctor, and I also have some predisposition to not being able to make or metabolize some B vitamins. And so I also pay attention to those. But again, like female health is, it's so multivariable and it's so different between individuals that this is really a place where personalized medicine and a woman's conversation with her healthcare providers is really important because what is right for me is likely likely not to be the right thing for you or for someone else. And I always encourage my friends and my sisters to really to find a good physician and to, to take all these things up and check them out on an individual basis.

For sure. Yeah. And I highly recommend as well, like, a functional medicine practitioner, because I love reminding people that those blood test ranges we see is actually a white man in the '60s in the United States. And I don't think many women are particularly—

you don't have to preach into the choir here. I did a whole webinar basically begging entrepreneurs to think about how to make a women's reproductive health diagnostic panel with the tools we already have. Because you're right, the part of the— I think part of the challenge is that you want to find a healthcare provider who can take those numbers and really interpret them through the lens of female health. Yeah, so important.

I love that. That's a good idea to do a worldwide challenge on women's diagnostic.

We have most of the tools available. We just need— we need someone to really aggregate them in a way that that, that does what I said, which is to consider a woman's body as a holistic whole and to try to optimize every part of the system in service of reproductive health. And then in parallel, to be able to measure those reproductive hormones more than we're doing now, which is right now we take the static snapshot at day 2 or 3 of a cycle, which is so meaningless. There is no such thing as a 28-day cycle. So day 2 of my cycle is something completely different than day 2 of your cycle. So what are we measuring anyway? But I think we need a way, an affordable way to monitor those hormones at a much higher resolution and then take all that information and put it into a package that actually gives women some information about where they are and what they can do to modify those things that are a little bit off.

I love that. We'll have an offline conversation about this because I have a few ideas.

I will say, aside from pills and supplements, I will say that I do prioritize my stress levels, right? So I, I have, I get massages, I have an acupuncturist, I definitely, I see a chiropractor, I definitely do things to, yeah, self-care. Yeah.

And I think particularly women who are in very sort of the jobs where they're like, okay, I want to focus on my career, I want to put in those extra hours and I'll freeze my eggs now and worry about fertility and conceiving later. Do still incorporate the self-care. I have to say that as well. Like I've learned from not doing it for many years to actually realizing the importance of it as well and just to reconnect with self. So yeah, thank you for expanding on that point as well. I think it's so important. I'd love to also discuss hormones, right? It's a very big sort of trend at the moment and bioidentical hormones in the UK that they call them partially body identical hormones and especially around perimenopause and with research saying that can happen from the age of sort of 35 and even I think post partum, right? So after having children, and I now researching this a bit more, really realized that this was happening to me, that my estrogen levels were completely crashing, which is not unusual after having children. And just to help women, like, how do you optimize for female longevity, women's health longevity through hormones? And what are some of the things that you are seeing that can be helpful? And as a follow-on point to that, how soon should one, or should a woman, consider looking at HRT if, for example, the estrogen levels are very low post having children, already mid-30s?

Yeah. Okay. So that's a, there's a lot to that question. So let's unpack. Let's unpack. Let's start at the beginning. Hormones is the topic. Thinking about hormones before menopause and in women who are of childbearing age. If you go and Google hormones cycle estrogen, what you'll find are graphs that show you over a 28-day— 28-day— over a cycle, they'll show you what happens to the hormone levels. And it's called a cycle because there's multiple different hormones. And hormone is a kind of a— it's a little bit of a confusing word because it really just means a signaling molecule that can travel over long distances. So it could be a steroid hormone, could be a peptide, could be a small molecule, could be a protein. And the ones that most people are talking about when they talk about reproductive hormones are steroid hormones. And the word steroid just means it's the name of a chemical. So I have a PhD in chemistry, so I'm just going to geek out here for a minute. But at a minimum, your audience should understand at least this. If you Google steroid, what you'll see is this beautiful ring structure. And it's just a, it's a scaffold and it's the basis for a lot of different compounds that we know about, like estrogen, testosterone, progesterone are the three that most people are aware of, but there's dozens of them. And essentially they they all have the same core structure, but then they're different around the edges. And those differences allow them to do different things in the body. And so estrogen, progesterone, testosterone are the ones that, that are most commonly replaced in hormone replacement therapy. But if you— in young women where everything's still working, at least to some degree, the levels of those hormones over time change dramatically. And those changes are really important for their function.

Right.

And anyway, so in younger women, I think issues with the levels of hormones can lead to infertility, can lead to undiagnosed conditions like PCOS. And so it's important that younger women keep an eye on those things. Now, after childbirth, certainly getting the system to reset and get back to normal cycling is again, something that's very variable between individuals. And when those hormones are at the wrong levels at the wrong times, it can dramatically impact your mood and your emotions. And that's because the part of the brain that regulates reproductive function, the part of the brain that those hormones are signaling to, is also the area of the brain that controls things like mood and emotion. So that's, that's why these things are all tied up together. That's why during our periods we experience mood swings. That's why during lactation and postpartum you might experience depression. And so it's really important to know that those are biologically based disorders and it's not all in your head. It's, these are real things. They're treatable and it's important to recognize them and talk to your doctor about them if you think you're experiencing them.

Yeah.

Okay. So that's in young women. That's what's happening in young women. Perimenopause, which a lot of women either don't know that's what's happening to them, or they have some sense that that might be what's happening. But then when they talk to their doctors about it, a lot of times doctors will just say, yeah, there's not much we can do. So. Good luck. And sadly, that's true, right? That's one of the reasons we're, we're funding research around the space is because we really don't know that much. But perimenopause is a period of time that can last anywhere from 1 to 10 years. And on average, that's 4+ years. And what's happening during that time is as the ovaries start to slow down and basically head towards stopping functioning, hormone levels can go all over the place. And again, that can lead to changes in your mood, changes in your ability to think leads to brain fog. It can lead to hot flashes. There's a lot of vasomotor symptoms that accompany perimenopause that we kind of sweep under the rug. But these are things that dramatically impact a woman's quality of life dramatically. And so if you feel like you're experiencing some of those things, it's really worth going to your doctor, having those hormone levels measured and asking whether or not starting some small amounts of hormone replacement therapy might be beneficial. So more and more I'm seeing doctors prescribing hormone replacement therapy starting in perimenopause. And there is— stepping back for a second and thinking about hormone replacement therapy, there has been a huge controversy around it that stems from a study that was published in 2002 that was based on a data set from the Women's Health Initiative in the US. Which I'm sure you and most of your female listeners at least are probably familiar with. And unfortunately, that initial study that was published got picked up by the popular press, and the headlines that were like Technicolor really brought forward were completely wrong. And again, I did, I actually did a whole webinar on this as well because I wanted to, and I did this with an OB-GYN as my co-host. And the reason I wanted to talk about it on a webinar was because so many women send me questions about it. And I wanted to show them, number one, as a scientist, how do I look at the scientific literature? How do I evaluate a paper when it's published? How do I decide? How do I look at the data that's in the paper and how do I decide whether or not it's, it's believable? What kind of statistics do I need to see? What kind of reproducibility do I need to see?

But also just to make the point as well, and I really implore people to look at who funded the research. And if you see that it was a pharmaceutical industry that, a pharmaceutical company that will benefit from a certain outcome of the study, then always just read with caution is what I recommend. But sorry, Jennifer, to cut you off.

I haven't even touched on this yet, but the global consortium that I co-founded and direct, one of the resources that we're trying to put out both for patients, for clinicians, for everyone is a knowledge hub. So in this knowledge hub, the way we're envisioning it is that it will be a resource for women to go to if they want to learn something about reproductive health, right? So that could be disorders of the reproductive system. It could be about the science around it. And what we're going to do is some of the content we'll write ourselves, but a lot of it we're going to curate because I have so many friends who will send me an email and say, oh my gosh, I just got diagnosed with PCOS. What do I need to know? And if they go into a Google search, they're going to go down. There's so much information out there and they have no way to filter it, no idea what's reputable, what's not. What's real, what's just garbage. And so what we can do is we can put it through the lens of science and medicine and say like, this is reasonable. Like what they've written here is actually correct. And then beyond that, we want to also have a section that would be about real-time research. What's going on right now? What are the big questions? What do we understand? What do we not understand? And what's happening right now? So stay tuned for that. We're doing kind of a beta version of it right now, but I think that'll be really important. Coming back to HRT and the WHI study, I think the study itself was flawed in the way that it was set up. And so the conclusions were really, in my opinion, not sound. And since then, since that study was published in 2002, there have been dozens of other studies, including from the dataset that they continue to collect data on, that basically showed that those initial headlines were wrong. And so I think a whole generation of women suffered because overnight Doctors stopped prescribing HRT, women stopped taking it. And as far as menopause goes and the negative health consequences of losing all of those health hormones, HRT is the best bandaid we have. It's not perfect by any stretch of the imagination. And I think this is an area of active research where I think there's a huge potential for improvement and innovation right now, like today, while we wait for those therapeutic, those discoveries that are going to lead to therapeutic HRT is by far the best thing that a woman who's going through menopause can think about. And again, it's an individualized thing where your genetic background, your risk factors really matter. And that's a conversation you need to have with your physician. But for women who don't have a predisposition to things like breast cancer, it really is the best option. And unfortunately, it's been applied like a sledgehammer. Like it has this kind of one-size-fits-all kind of mentality about how it's administered. And that's unfortunate because a lot of women will start it, have side effects because guess what? They're getting doses and cocktails that aren't right for them. And then they'll suffer because they're not replacing those really key hormones. So what I always say is it's important to talk to your doctor and to really see where you are personally. The last question you had was around age of starting HRT. And there are, I think there's really solid research out there to show that it's important to start HRT as close to menopause as possible. Some women even slightly before they go through menopause. And the reason for that is all of those hormones. So estrogen, progesterone, testosterone, and I will say a lot of HRT doesn't include that third piece. So you really need, if you have a uterus, let me back up. If you still have a uterus, um, and hopefully most women do, if you still have a uterus, it's important to include progestin or progesterone compounds in the HRT because that protects against endometrial cancer. But a lot of HRT combos don't include testosterone. And testosterone for women is actually really important for a lot of different things, including sexual health, but also overall health. And if you're taking HRT and you don't have testosterone included there, you might talk to your doctor about it. And then I think there's pretty good science to show that if you don't start HRT very close to when you start to lose those hormones, what happens is the receptors— there's two pieces to hormonal signaling, right? There's the hormone itself, which is traveling from one place to another, but in the target tissue, in the cells where it's trying to signal, there has to be a, like, catcher's mitt to, to basically to send senses— it's like a sensor to sense that the estrogen or the progesterone or the testosterone is there. And if it's not there for a long time, those sensors, they get downregulated, and eventually they stop being made. And once they stop being made, they're not coming back. So you need— essentially, if you don't have those hormones for several years, they go away, the sensors go away, and you don't get them back. And then if you add in hormones without the receptors, that can have a negative consequence. So the research that I've seen says that you should really try to start within 6 years and that after 6 years, in fact, after 10 years, that it can have a detrimental effect to add back HRT. So there is a window of opportunity there.

And I wonder, thank you so much for expanding on that. And I wonder, because I, and I'll tell my personal side of things here. So I'm 40 and I was— you don't look 40. Thank you. I'm biological age of 26, according to GlycanAge. So I'm trying to get 20 years old, but I'm actually participating and I put myself as a a bit of a guinea pig with a clinical trial that GlycanAge is doing together with Dr. Louise Newson, who has the world's largest perimenopause clinic, who I'm sure you're familiar with as well.

I do know Louise, yeah.

Yes, exactly. And so I decided to sign myself up for this because there is no research around starting HRT, body identical in the UK HRT, and repeated testing was showing that I had pretty much no testosterone since this is now mid-30s. So I think my levels were so depleted. I was struggling to get through the day, which is part and parcel with it as well. And then I did the Dutch test, DUTCH, for those interested here in the UK, you can just order it online. You do it yourself.

This is the, just for everyone who's listening, this is a way to measure your hormones at a very, at a really high time resolution. The problem with those tests is that they're so expensive. That's what I was saying. We need to find a way to lower the price of those things for everyday women.

I think as well, a lot of people are like, oh, these things are expensive. It depends. Maybe in the US it's a lot more than here in Europe. However, the lifetime value of that—

I agree, but some women just can't afford $500 or $600 out of pocket.

Yes, it's $270. Exactly. Yeah.

So it was a different price point.

So I think in the US that they're good at charging, right? But depends where you are in the world and listening as well. And there are other tests and potentially your insurance might cover it. It depends on your country where you're listening from. But what was clear from that was that my estrogen levels were not optimal. My testosterone was pretty much nonexistent. And so I decided decided to sign myself up and I'm taking very low dose of estrogen and testosterone. And straight away, within a few days with the testosterone, I didn't have this complete like exhaustion midday already. That helped a lot as well. And with the estrogen, one of the benefits is that my biological age is reduced by 4 years since I started taking it. So I think that already is great and love to understand the correlation also with ovarian aging, if at all. I don't know if that's the case. I know that there isn't that much research around taking it too early, but have you seen anything in terms of picking up or starting low doses of bio or body identical HRT to prolong the healthy lifespan, the fertility lifespan? Have you seen anything around that?

Certainly there's evidence that replacing the hormones that are lost when your ovaries stop functioning is beneficial for overall health. What's missing and what, what should have already been done, but what hasn't really been done in a rigorous way, is long-term longitudinal studies that monitor women starting before menopause all the way through. And it's really, it's a travesty that we don't have that data. And that's, that's the reason that we started everything that we're doing is just because these are not, these are like the questions you're asking are very reasonable and we should be able to answer them. We just don't have the data. So we need to collect that data and, and we're correcting a century-long error. And just ignoring women's health. So yeah, unfortunately these days, a lot of the answers that I give people are, we don't know, we need to collect that data. Luckily there are people like Louise and others who are, who really understand that this is important and who are starting to generate these large-scale datasets that, that can help. And yeah, I have high hopes.

I'd love to jump into looking at what you are doing amazingly with the Global Consortium of Reproductive Longevity and Equality. Can you explain what your mission is there and the different sort of project and research areas that you're looking at?

Yeah, absolutely. The Global Consortium— so it is meant to be global— for Reproductive Longevity and Equality. It's a mouthful, right? This doesn't really roll off the tongue. Powerful words. But every piece of it is important. So for us, reproductive longevity is really just about understanding what causes ovarian aging. What is the causal causal thing that sets a woman's ovaries to start aging in her late 20s and early 30s. We don't know what that causal thing is, and it's something where if we could understand the underlying causes, we could potentially develop interventions to slow it down or get rid of it altogether. And people like latch on to that last thing I just said and say, oh, she wants to get rid of menopause. And that's true. Like in a moonshot way, if I could have anything I wanted in the world, I would definitely get rid of menopause. Cause. But there's a lot of nuance to thinking about this. And really, ideally, our goal at the consortium is just to accelerate and facilitate taking those really fundamental discoveries that happen and translating them into products and therapies for women, full stop. That's it. We want to make things go faster. And the way that we do that right now is we fund grants to scientists all over the world. And the reason that we're doing that is because there has been just horrible underfunding of women's health in general, but especially women's reproductive aging. There just hasn't been a lot of money in the space. And as a scientist, as someone who runs a research lab, I can't work on a problem. It can be the most exciting and interesting scientific question in the universe, and I can't work on it unless I have grants to fund it. And so we saw this as a real, as a, as an urgent need. And with the very generous donation from seed funding from the Bia Echo Foundation and Nicole Shanahan,, who's been an incredible partner in this, and she's co-founded the consortium with me. We are funding scientists all over the world. Part of what we're trying to do with our funding is to stimulate research in the area, but we're also working on providing a lot of resources to our grantees and also to our center members. So this all started because Nicole came to the Buck Institute. She was really prescient in understanding that this was an urgent issue for women, and she asked us at the Buck Institute if we would be willing to start a center, like physically at the Buck to study female reproductive aging. And I became part of that center. And then as soon as we started it, we realized that if we were going to have a true impact, we really needed to do something bigger. And that's where the consortium came in. There's a second center that we started in Singapore. So at the National University of Singapore, the Asia Center for Reproductive Longevity and Equality. And for the center members and the grantees, we spent a lot of time thinking about what can we do as a, as a partner to help these scientists do things faster. So part of that is building a network. And I think about this as if I want— essentially, we need an army of creative scientists, but then we also need to pair them with clinicians, right? And this is a conversation that historically doesn't happen very often in science, right? Scientists tend to like to talk to each other and to be a little bit, I don't know, standoffish with other people, including clinicians and, and biotech and pharma. And so I spend a lot of time actually building out the network of people who are interested in this space. So that includes literally anyone with an interest. You, Claudia, are an ambassador. We need ambassadors, but also people like Louise Newsom, clinicians who actually have the patients, the scientists, obviously, but also fund early-stage biotech like Nina and potential founders. And we're trying to build this ecosystem in a way that, that is different. From the way that things have been done before. We have a website. You're welcome to go there. You can read about the things that we're doing. You can join our network.

Can you share the website with my audience so they know?

Yeah, it's just gcrl.org. G-C-R-L-E dot org. And that last part, I will just say the last part, the equality part, I personally really see this as an issue of equality. We're talking about half the population here, right? If a woman is lucky enough to live to midlife, she will undergo menopause. It's unavoidable. It's like death. There's no escaping it. And as we start to extend healthy longevity, which is what the Buck Institute is trying to do and what aging researchers all over the world are trying to do, as we make progress in extending healthy longevity, if we don't address reproductive longevity, then suddenly women are going to be living more of their lives after menopause than before. And menopause does have a detrimental effect on even healthy women. Risk for all sorts of things like cardiovascular disease, osteoporosis, stroke, cognitive decline. There's just a lot of things that happen that don't need to happen. So we think the things, the advances that are going to most rapidly lead to, to progress in this space are going to be through collaborations between academia and industry. So for me, the equality piece is really about the fact that every aspect of an adult woman's life is influenced by the fact that she's going to go through this reproductive decline in the middle of her life. And this typically happens right at the moment when most women are reaching the pinnacle of their careers, if they have careers outside the home. And it just, it impacts every aspect of their lives, whether they want to have biological children or not. For me, from the moment I went through puberty, the ticking biological clock in the back of my mind influenced my career decisions, my education decisions, everything. And men don't have that. They just don't. And this is something where I think if we could extend, if we could extend the number of healthy eggs that a woman has at age 40 by 1% or 2%, if we could change those numbers and push out the age of menopause by a few years, that would be a game changer for women. It would be profound. And that's just, that's like the lowest, that's the lowest thing that I hope to achieve.

What do you see as the biggest opportunity and what are the biggest challenges in achieving that, Jennifer?

Yeah, the biggest opportunity, I think there's two opportunities that I think are really achievable right now. One is to make this something, to make this a topic of discussion that is on everyone's mind and not just women. This is an important thing for men to understand as well, and not simply because they have females in their lives that they care about. This is important for men because there's a genetic component here that's important for longevity for both men and women. And there's an economic component here, which we haven't discussed at all, but cost of menopause is profound and it's growing, right? The number of women in menopause by 2025 globally will be more than a billion, which means that's over 10% of the world's population by of that's going to be women actively in past menopause, and there are healthcare costs associated with that. And finally, as I mentioned before, understanding why ovaries age prematurely is going to tell us something about aging in the rest of the body in both men and women. And so this is something— the opportunity here— we are at a historic moment. There is a groundswell of interest in the space, and we're at a historic moment where we can actually change something for real in, in women's lives. And so I want this to be— I want this to be conversation that is had around every dinner table. I want everyone to understand what ovaries are and how they work and what happens with age. That's opportunity number one. Opportunity number two is to really change the world. Like, we have the opportunity to discover something that will make a difference in the lives directly of half the world's population. That's profound. The challenges are what I already mentioned. Funding is a huge challenge, and particularly for basic research. I think one of the things we're trying to do with our grants, like I mentioned before, is to really think about them differently. I'm measuring progress not in papers published and talks given at meetings. I am measuring progress in how quickly we can move something into the clinic, whether that's a product or a therapy, and, or many products and many therapies. And I think one of the big challenges in funding scientific research is that me as a scientist, I have to get many different grants to fund my lab. There's none that are long enough, there's none that are large enough to actually fund all the science in my lab. And I'm basically like a, a lot of people don't understand how science funding works. I'm basically like a small I have to bring in the money to fund all of my people's salaries, all of the equipment, all of the supplies, everything, my salary. I bring that money in. The institute where I'm housed kindly gives me space and support for grants and HR and facilities, and I fund my research. And so what we need really is sustainable funding because what happens right now is that I have this patchwork of grants. Grants that are partially overlapping and different lengths of time and different amounts of money. So many different patchwork grants, and I'm constantly having to apply for new funding to fill the gaps. And what that leads to is really incremental progress, right? Because every few years I have to slightly pivot my research program to fit a call for funding, right? Because I need to be able to get that money. And you know what we need is sustainable funding. We need to fund science scientists. We need to fund the lab and the scientists themselves, not specific projects, right? Because what happens with grant funding is I'll apply for a grant that is for this little tiny thing that, that some foundation or the NIH thinks is important, when really, like, I know what's important and I need to be able to follow where the research takes me, right? When I get an experimental result that disproves my hypothesis, I need to be able to pivot to do something else. And beyond that, I need to be able to, to think creatively, and I can only think creatively if I have a runway that is, that's like in sync with how science works. And it takes more than a few years usually to get really important results. So we're trying to think about how to structure our grants. And for the next few rounds, what we're going to do is we're going to have a pot of money that's for new grants because we want to keep bringing people into the space, but we also want to have a pathway for existing grantees to get sustainable funding. So yeah, funding. And the other challenge really is that there has been a systemic bias both in society with taboos around talking about women's health, talking about periods, talking about menopause. That's been, that's been forever really something, a conversation that's been hard to have. We're trying to remove those taboos, but there's also been a systematic bias towards males in biomedical research, a sex bias. And that's also changing. But again, these things have really held up progress.

Progress. Yeah. And I think some of my listeners will know I did an episode on unleashing women's superpowers by understanding the female biorhythm, that the FDA in 1977 actually made it illegal to have women of childbearing age in clinical research. And even though that was reversed in 1992, the gold standard had been set. So a lot of research is not around women as well. So what I think, what I hear sometimes is like, oh, but the menopause, it's just part of being a woman. But why Why could that be optional? Can you expand on that?

Sure. We're one of only 5 species in the animal kingdom that go through menopause. So it's us and 4 species of whale that go through a true menopause. And that tells me it's not a biological imperative. There's plenty of species that don't do it. And I also want to make a distinction here because a lot of women, they'll say to me, I don't want to have a period forever. Ever. And I'm like, me neither. I want to separate fertility— having a period is really important for setting up your uterus every month to be ready for a potential pregnancy. That's what it is. And when you have your period, you're shedding essentially the uterine lining that was built up in anticipation of a potential pregnancy. It requires a lot more than functioning ovary to be pregnant. And I think that it's probably going to be possible to separate the beneficial effects of having those hormone on your health from being fertile until you're 70. Although I have to say, I also think it's none of my business. If you want to have a baby when you're 70, that's your business, not mine. But I do think they're separable. And yeah, I think there's no reason to think that we need to have menopause. One of the scientists that we hired into the center, her name is Dina Amira at the Buck Institute. She is an evolutionary biologist who's been working on questions around the evolution of female physiology for her entire career. Career. She studied the evolution of pregnancy, the evolution of menstruation, and now she's looking at the evolution of menopause. And she's just finished a popular science book, so a book for the general public about the evolution of the female form, which will come out in the spring. And I did a webinar with her because these questions about, like, why do we even have menopause? That's a big question. And if we could answer that question, we would be a lot closer to knowing what those causal factors are for ovarian aging. Listening to her talk about this is fascinating.

Fascinating as well, especially I think, I don't know when the lifespan of women shifted from below 40 to above 40 and then why that wasn't incorporated. So it's when that sort of menopause first historically appeared when humans became older or females became older as well.

Yeah. There's more nuance to it than that though. I used to, yeah, there's a lot of kind of simple explanations that we could reach for that probably have some truth to them, but it turns out to be more complicated than that.

Okay, I'm sure it is. This was—

yeah, and I'm not an expert in this space, and so I try very hard not to, to basically to send people to talk to Dina about this.

Exactly. I would love to ask you, Jennifer, what would— in an ideal world, you could get all the funding you want— what would be some of the most exciting aspects of improving women's health and female aging that you would most look forward to if you could create it all?

Ah, if we had infinite funding, the kinds of— you can go to our website and see the grants that we're funding. We had our first round of funding in 2020. We skipped a year because of COVID because a lot of people had to shut their research labs down, but we're literally on the brink of announcing the next round and we'll be giving away grants every year. The kinds of things that I think are most exciting right now are really in the biomarker and diagnostic space. I genuinely think we can do a much better job of helping women understand where they are in their own reproductive span trajectory. At a minimum, I should be able to know how close or far away I am from menopause. Come on, that's not possible right now. I think finding a clock, or maybe several different clocks, for ovarian aging is going to be really important. I think doing the discovery to understand what the signatures of ovarian aging are in humans. That stuff is fascinating. And the goal really is to find those therapeutic targets, to find those— that causal factor. Or maybe it's a bunch of different things that work together, right? Some constellation of cues or timers that's important for setting that reproductive decline in motion. I think that— I think that those exist. We just need to figure out what they are. I'm really excited about, about, about the cellular targets that we have on the horizon. I want to caution people to, to really to be clear that we are in early days here, right? Like we really are at the beginning of a discovery piece and we need to focus on the basic research to do the R&D to generate the IP. I think on the 5-ish year timescale that, that we will have made some of those discoveries and then we can start to look towards towards commercialization and privatization. But right now what makes sense is funding basic research. So yeah, I, I think it's frustrating to me that this stuff hasn't already been done, but I'm also really heartened by the interest. There's a level of excitement and enthusiasm from everyone that makes me very optimistic about what's happening right now.

So exciting. Jennifer, for my listeners interested in understanding women's reproductive longevity better, what is a good online resource or book, for example, that you would recommend they start with?

Yeah, we did. We have a white paper that we wrote for a non-science audience that's maybe a good place to start. Yeah, it's online. It's on our website, gcrl.org. And then obviously I'm going to recommend Dina's book when it comes out, which is really bigger than just reproductive aging. It really focuses a lens on all of female physiology. And then we're including links to resources on our website for trusted partners that we really think are putting good information out. For example, the National Menopause Foundation, which was founded only 2 years ago, if you can believe that. It's the first nonprofit like we are. It's the first nonprofit organization that's just for women, just for patients. It doesn't have any links to any professional societies or any other commercial entities. And they've done a really beautiful job of curating a community. There's a, there's a community you can join to talk to other other women. They also have a podcast called The Positive Pause, and they, they link to resources online. And yeah, I would start there. And I think anyone who's interested in the space, whoever you are, we— like I said, we need ambassadors. So if you're interested in joining our network, please reach out, get in touch. If you're an investor, anyone who, who wants to— who has philanthropic dollars to give, we're always looking for as much money as I can raise. That's money that we're going to give away to scientists. For entrepreneurs in the space and for investors who are interested in companies, I do, I do spend a lot of time matchmaking, but the truth is I don't see a lot on the therapeutic side right now. It's all on the product side. At some point in the future, we will try to stimulate accelerator-type support for private companies in the space, but we just aren't there yet. Like, we really don't have the IP necessary, and there's precious few companies that I can of maybe 3 or 4 total that are doing something really relevant and important on the therapeutic side. I'm also— I spend a lot of time talking to direct-to-consumer companies who have products for women, and we're trying to— we're asking them whether they would be willing to include our QR code for direct funding, like adding a little line at the checkout workflow that says something like, would you like to donate money to research aimed at understanding ovarian aging or making menopause optional? So I would love to collaborate with anyone who's interested in helping us.

Wonderful, that's brilliant. And where can people follow you and what you're up to online, social media handles, etc.?

Yeah, I'm on Twitter, my handle is Jen Garrison, J-E-N-G-A-R-I-S-O-N. I'm on LinkedIn, Dr. Jennifer Garrison, and we have an Instagram for GCRLee and a Twitter handle as well for GCRLee, it's GCRLee1. So yeah, and I would love to hear from anyone. I'm very happy happy to really to give talks and to connect with anyone who has an interest.

Excellent. Thank you so much, Jennifer. I'm going to link all of those in the show notes. Do you have any final ask, recommendation, or parting advice for my—

I would just say learn, do as much as you can to learn about where you are, and if you're interested, please reach out. I think we have an opportunity to really change things, and for the most part, this is women women self-organizing. The person who is my, my right-hand person— I have two right-hand people with the consortium, and one of them is a man. So if you're a man interested in this space, also get in touch.

Amazing. Jennifer, thank you so much for coming on today. It's been an absolute pleasure.

Yeah, thank you so much for the opportunity and the discussion. I really appreciate it.

Thank you, Jennifer.

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