Cracking the Code of the Female Fountain of Youth: From Hormones to Neurons with Dr. Jennifer Garrison

 Welcome to another episode of Superhumanize, the podcast that dives deep into the realms of health, wellness, and longevity. I'm your host, Arianna Summer, and today we are journeying into the microscopic landscape of our biology, specifically zeroing in on the secrets of female reproductive aging. This episode is not just for women, but for anyone interested in the complex dance between aging and vitality and how the body's smallest components can have grand ramifications on our overall well being.

My guest is an illustrious figure in the field of aging research, Dr. Jennifer Garrison. She's an assistant professor at the Buck Institute for Research on Aging, the world's first institution dedicated solely to unlocking the mysteries of aging. Her groundbreaking work also extends to her roles as Assistant Professor in Residence in Cellular and Molecular Pharmacology at UCSF and Assistant Adjunct Professor at the Leonard David School of Gerontology at USC.

In her laboratory, aptly named the Garrison Lab, Jennifer and her team explore cutting edge topics like neuropeptide signaling, The role of neuropeptides and aging, and particularly for today's conversation, the role of the brain and ovarian aging. Their work brings a whole new dimension to how we perceive and understand menopause, essentially shifting the paradigm and pointing to the brain as the epicenter of this life altering transition.

Now, why should you care? Because this research could redefine the way we look at aging, not just for women, but for everyone. From the rapid aging of ovaries to the global effects that menopause has on bone health, cognitive functions, and even cardiovascular well being. Jennifer's work has profound implications.

So if you've ever wondered why reproductive longevity is crucial, what menopause may signal about your overall lifespan, or how future research might completely eliminate the need for things like IVF and egg freezing, then buckle up. We'll also delve into the controversial topic of hormone replacement therapy, discuss the potential risks and benefits of having or not having children, and envision a future where antifibrotic drugs and high quality oocytes could redefine what aging means for women.

Get ready to have your mind expanded and your perceptions about aging and vitality redefined. This is a conversation that pushes the boundaries of what we know and ventures into what could be possible. Let's superhumanize.

 Jennifer, thank you so much for joining us today. It's a pleasure to connect with you.

Oh, thank you so much for having me. Good to be here. You

are someone with incredible credentials and you specialize in some really fascinating fields. I've already mentioned it in the introduction. Amongst other, you're also an assistant professor at the Buck Institute for Research.

on aging. You're an assistant professor in residence at the cellular and molecular pharmacology UCSF, and you're an assistant adjunct professor at the Leonard Davis School of Gerontology. You had an interesting start with regards to How you got into science, if I'm informed correctly. Is it true that initially you were inspired to become a scientist because you wanted to cure AIDS?

That is true. Wow, you did your homework. That is true. I had I had an unusual childhood, and many of my male role models were gay men who, I grew up on the East Coast outside of Washington, D. C., and in the early 80s many of them got sick and died from AIDS. And so I was hyper motivated to try to find a cure for AIDS.

And, as a teenager, as a... A high schooler and then an undergraduate. That was my, that was my initial goal and interest in science. I quickly learned that I'm really not adept at understanding the immune system. It, at least when I was learning it in the 90s, it was really plagued by a lot of jargon and a lot of complicated stuff that just didn't.

It just didn't work with my way of thinking. And so I continued in science. I love science and I had a real passion for it. But I went on to just pursue areas of biology that and chemistry that that resonated with me.

Your lab, the Garrison lab focuses on truly fascinating.

And from my perspective, absolutely cutting edge fields such as neuro peptide signaling neuro peptides and aging and the role of the brain in ovarian. aging. So also the aging of the female reproductive system and the latter is what I'd really love to focus on today. And I'd like to start with a question.

Why is reproductive longevity so crucial?

Ah I think for reproductive longevity and really anyone who happens to have a is it's correlated and connected to overall health and also overall longevity. So when we talk about studying aging, our goal really is to understand how to extend health span, meaning the number of years that someone is healthy rather than extending lifespan.

Our goal is not. necessarily to make people live to be 800. We want to take the lifespan that we already know humans can achieve and hopefully make as many of those years healthy as possible. And so as we're thinking about how to do that I think that over the last decade or more basic biological discoveries from scientists all over the world have really shown us that biological aging, not chronological aging, but biological aging is malleable.

And since aging is the number one risk factor for many of the chronic diseases of the modern world, we think about targeting aging as a way to target many of these age related diseases simultaneously. And as we're, thinking about how to extend healthy longevity, I think. If we don't also think about understanding and extending reproductive longevity in females, then we will make inequality between the sexes worse, not better.

And that's because aging in the female reproductive system is It's really, I think, understood by most people as having the downstream consequences that we observe in terms of challenges with fertility and birth defects and things like that, miscarriages. But on the other side of things unrelated to reproduction aging in the ovaries, essentially.

changes a woman's risk factors for her overall health. So when ovaries stop working in the middle of a woman's life that really has profound impacts on her overall health. And so from my perspective it truly is an issue of equality and it's something that we have neglected for a long time.

I love that you see this as an issue of equality, Jennifer, and what you're saying actually also goes hand in hand with some of the things a, another guest I recently interviewed Dr.

Steven Austin said that he's a biologist focused on aging, especially in wildlife. And

I know, Steve,

Great. Yeah. So he basically said that, nature doesn't really care about us living really long. Nature cares about procreating. And so as soon as we're not capable of reproducing anymore, that's also when, in a lot of cases, these diseases.

Start setting in 'cause it's directly tied to aging. And so what really, I'm curious, why do ovaries age faster than other parts of the body?

Yeah, that's a, that's the key question. And I would say that's the thing that we really don't understand. So obviously ovaries are one of the organ systems that distinguish males from females.

But we really. don't know that much about how they function, and we certainly don't understand how and why they age prematurely. But what we do know, and what is obvious to every human on the planet, is that if a female is lucky enough to live to midlife and beyond, then they absolutely will be impacted by reproductive aging, right?

It's characterized, we can we can describe what happens. It's characterized by a decline in the quality and the number of eggs that are contained in the ovary. And this happens it's one of the most robust signatures in human health that it will happen to every single woman. who reaches midlife, no woman will escape menopause.

And ovaries, we think about them a little bit like the canary in the coal mine for aging. So they're aging at about two and a half times the rate of the rest of the tissues in a woman's body. So what that means is that when a woman is in her late twenties and early thirties, when the rest of her organs are functioning, at or near peak performance, her ovaries are already showing overt signs of aging.

And what we want to understand is why this happens, number one there aren't very many species that go through a menopause in the middle of their lives. And so it's not a biological imperative, so we don't know why it happens and how it happens. So what are the triggers, the causal factors that are underlying this early aging in ovaries?

And I think if we could answer those questions, then we could potentially intervene to try to mitigate some of these negative health consequences and risks that happen as a result of ovarian aging.

That makes complete sense, Jennifer. And you just mentioned there's not many other species that have this type of menopause in the middle of their lives.

Can you name some of those that

do? Yeah, actually, it's really, it's a very small list. It's humans and some toothed whales. So shortfin pilot whales, belugas, killer whales, and narwhals. So one could argue the coolest whales

And and then there's some debate about whether rhesus macaques, which is a species of monkey goes through menopause they have some features of menopause, but other features they don't have. And then I think I heard recently something about maybe giraffes go through menopause, but there's very few species that really go through a true menopause.

So we are definitely in the minority and we do not understand why this is an area of active research to try to understand what the differences are between the species that go through menopause and those that

don't. Yes. And I also would be interested in what your take is on, of course, menopause.

There's a lot of talk about menopause and it's actually also a market within the supplement industry or wellness industry currently that a lot of, famous individuals such as for example, Gwyneth Paltrow or others who have made themselves a name and that's fear are talking a lot about, which is great.

Thank you.

It's amazing. I think it's incredible how much attention this area of biology is starting to get. And I think it can only be good, whether they're saying things that are that are right or wrong. I think that the attention in this space is really important. Yes,

that it becomes a normal part of the cultural conversation.

And also something, what I'd like your take on is, I think something that really is not talked a lot about, even though there's people that say, this is actually also very interesting. It's a little segue off from our main topic, but is that men actually go through something similar that's called andropause.

But it's really not in the zeitgeist and most people are not even aware of this, that these shifts and hormones and bodily functions also take a toll on men. However, with men, there's still the propagation, of course, that as a man, you function until perfectly until you're. 267 years old.

So what is your take on that?

Yeah, so I think there is no question that aging occurs in the male reproductive system as well. No question about that. The real difference between Aging in the female system and aging in the male reproductive system is that, and males aging in their reproductive system is synced up with aging in the rest of their body.

So if you just consider like organ function over time, there's this kind of gradual decline out in the 80s and 90s later in life that happens in all of your organ system. And aging in the male system happens synced up with aging in the rest of their bodies. So I think it's super misleading.

Andropause is real, but it's super misleading to make any kind of equivalency between what happens in males and females. There is a decrease in testosterone in men that starts to happen sometime between age 30 and 40. And after 40 it declines at a rate of about 2 percent per year. And so that there, that, that decline in testosterone and the decline in reproductive function, it's really gradual and it happens, at the same rate as the aging in the rest of a man's body.

So I think it's It's, some people will call it the male menopause, which is deeply misleading because it suggests that those symptoms are some results of a sudden drop in testosterone middle age, which simply isn't right. And it's also I would say. It's a sort of thing that, that in some ways diminishes what's happening in the female system.

There really isn't any equivalency. Having said that though, it's real and I think it's very interesting and certainly once we've figured out female reproductive aging, we will move on to male reproductive aging. Great, thank you. It's like an insidious form of gaslighting in a way because because it, It really diminishes what happens to women at menopause.

It's dramatic and it's precipitous and it happens right in the middle of life and it's just not the same thing.

Thank you for clarifying that for us, Jennifer. And we're, of course, back at the, with the issue of equality. And so is it true that you can make a prediction on overall lifespan based on when a woman enters menopause?

Is that correlated? Is

that correct? That's correct. We don't understand why, but there are now many studies. Showing that there is a correlation between age at natural menopause. This is important to say we're not talking about menopause induced by chemotherapeutics or things like that, but age at natural menopause does correlate with a woman's overall lifespan.

And, again, we don't understand why, and if we did, if we could understand why, that would be a huge hint in terms of, what the underlying causes of reproductive aging in women are. But it's fascinating that it exists, and it's maybe of interest to the men in your audience that women who go through menopause later in life tend to live longer.

And that extends to their male brothers. So there's a genetic component there that we don't fully understand, but that clearly impacts both sexes. Interesting.

Fascinating. And how about, so I mentioned, menopause is getting talked about a lot today, which is fantastic. And there's also another term that's popped up in the recent two or three years more into the, awareness of the general public, and that is perimenopause.

And How to, manage perimenopause and by managing that in certain ways, also potentially pushing menopause out further. What are your thoughts on

that? Yeah I guess it's important to define menopause here. Menopause is a single day in a person's life. It really is defined as the day on which you haven't had a period, a menstrual cycle for 12 months.

So it's a single day and everything before that day is characterized as perimenopause. And everything after that is considered postmenopause. So perimenopause is a period. Period of time that can extend up to 10 to 12 years. It can be very short or it can be very long and it really does change and fluctuate depending on the individual, but it's a period of time leading up to menopause when the number of eggs and the quality of eggs has declined to a point that the hormone levels that are normally being orchestrated by the ovary, they're slowly going down.

Basically, ovarian function is going down, but it doesn't, at the level of the individual, it's not just a single dive off a cliff. It's really fluctuating in a really dramatic way and it's fluctuating and also declining at the same time. And so at the level of the individual, perimenopause is characterized by a whole host of really dramatic.

Symptoms that extend from basal motor symptoms like hot flashes to things like cognitive decline and brain fog and, these are not life threatening for the most part symptoms, but they do greatly impact a woman's quality of life. They greatly impact a woman's ability to function and potentially do her job.

So it's a time that's characterized by by a really dramatic and important period where, you know, we don't understand how to mitigate those symptoms. We don't understand we don't fully understand why there's so much variability between individuals. That would also give us a clue about what the underlying causes are, if we could understand why it's so variable between individuals.

But, women are coming up against perimenopause, women of my generation and your generation and the generations just right up in front of us. And. Rather than, accepting it as a natural part of life, saying, Wait a second. This is not okay. And trying to find solutions that will help them get through this period.

Certainly. And I am most grateful for all the work you and your team doing, Jennifer. It's much, much needed. And as you said, these symptoms can for some people be also not just vexing and uncomfortable and impede. To really function at your highest level and experiencing the highest form of wellbeing, but they can truly also be debilitating.

Yes. They can be very debilitating and there isn't a lot of education for women around what they can expect during perimenopause and menos. And most women end up discovering, what perimenopause is when they start experiencing symptoms, and that is not okay. And, many women don't get sufficient information or potential, Interventional sort of therapies from their physicians, which is also

not okay.

Not at all. It really strikes me that something that is so important and fundamental that it's not at the very least in the most basic ways addressed in biology class at school, just so this becomes part of the awareness and that this is something that happens in life. And so that there's at least an intellectual lead into the.

topic

later on. Yeah, there's a dramatic need for education both on the part of individual women, like we should be educating women, in their early 20s about their bodies and about what, what will happen to them later in life. So that, that not because we want to encourage them to have babies when they're young, but just.

Because as they move through their adult lives, we want them to be armed with all the information they need to make informed choices about their careers, about their health, about their families, everything. But on the other side, I think we could do a much better job educating physicians. I don't think there's a very much information included in the first four years of medical school, at least in the US around women's health in general, much less reproductive aging.

And I think that there's a huge opportunity there. We're spending some time on that with the consortium that I lead.

Fantastic. It's an incredible opportunity. And it just ties into with it ties in with other things that have just not really gotten addressed until the very recent past.

Something that comes to mind is education on what the clitoris exactly is.

Knowing what your anatomy is, how it works. Where it is, what it's for.

It boggles the mind.

It boggles the mind, I

agree. Yes, and of course, if you look at the more esoteric, spiritual side of things, we've, lived in a culture for the longest time that has propagated youth and youthfulness, especially as something that women must be in order to be revered accepted members of society.

And if you look at other forms of societies and older cultures where the maiden or mother crone, all three of these emanations of the woman as her being were revered. I think we hopefully are getting slowly closer to this. I see this all across, whether it's in literature, whether it's an. pop culture.

You look at Hollywood movies and actresses of a certain age reprising leading roles and standing fully in their womanhood unapologetically. So it's a beautiful thing. We still have a lot of work to do on all these fronts. And science is of course leading the way in so many ways. I know that some people in the audience are probably really curious about, okay, we understand there's this thing called menopause. There's perimenopause. Is there any way, are there any tools or, exams or tests that can help us assess where we are right now within this reproductive

health? I will first, let me just say that I agree with you wholeheartedly that that we need to spend, we need to have a shift in the way that we, Revere and appreciate women who are in the second part of their lives.

I think there is a shift that's happening, there are societal taboos that are falling around talking about women's bodies and the things that happen to women's bodies, but there is still this, I don't know, this silent It's almost like a discrimination against women of a particular age once they pass a particular age that isn't, that's not shifting as fast, I think, as the taboos around talking about sex and periods and menopause even.

So I'm with you on that. In terms of having tools to essentially eliminate a woman's either fertility status or to tell her where she is in her reproductive span, right? Because, reproductive span is just, the time between. Between when you start your period and when you go through menopause and we have almost no Tools to tell you where you are in that trajectory And that's horrifying and really it's disappointing and it's also super frustrating as a woman But I would say that these things are changing.

So I think that on the horizon those are the most Those are the lowest hanging fruit that we can achieve as scientists and entrepreneurs. It's just coming up with a way to redefine diagnostics to rethink the fields and to rethink how we how we measure. a woman's trajectory, right? The tools we use right now are really I would say rudimentary.

We take temperature, we do blood tests on a particular day of a cycle that may or may not be, almost certainly is not 28 days. So we take this very sort of static picture of what is an incredibly dynamic and fluctuating system. And this is a place where I think we should have An easy a noninvasive way to know where you are in that trajectory.

And I think that we can do that pretty quickly. But right now, there's really nothing great out there. There's a lot of stuff under development. So there's, I would say that the message is positive. There's quite a few companies working on this. I know there are some academic labs working towards finding better biomarkers and diagnostics.

But truly we are missing even that most fundamental thing, just being able to know to take measurements to know where you are in your reproductive span. We really don't have those tools right now, unfortunately.

What do you think the time span is on

that? Oh, I think it's going to happen very quickly.

I hope within a few years, we'll have things that will be much better tools than what we have available to us. Now, certainly, when I was, when I started learning about this space a while ago now, but when I started learning about this space, I obviously had questions about my own And I have to say, I have not found anything.

I tried lots of things and I haven't found anything that really gives me a definitive picture of where I am.

Let's hope this the day comes sooner than later when we have tools at our disposal and Jennifer, you are, I would dare say you're on a mission to eradicate moon flaws.

I want, moonshot goal.

Huh. And certainly that's a good, that's something that people latch on to. But I really, what I want is for us to devote dramatically more research funding and dollars both on the academic side and on the private industry side towards women's health, period. It is, it's criminal how little money goes towards understanding the health the diseases and the health.

Things that impact women. And in terms of research, like What we fund in science creates what we know and the research funding for women's health for reproductive aging, in particular, but for women's health in general has been poultry. We're talking about half the population and, the money devoted to, All of women's health at the National Institutes of Health, which is the largest biomedical research funding body in the U.

S., has been at the level of maybe 15%. And it inches up each year, so it's getting better, but that is not nearly enough. And for reproductive aging, that number has been like a rounding error, less than 0. 1%. And we know there have been really beautiful and comprehensive studies done. The one that comes to mind is the WHAM report, which shows that for every dollar you, you devote to women's health research funding has huge knock on effects in terms of economic impacts.

I think it was. I hope I don't misquote them but it was something like if you were to invest 350 million into women's health, which is not very much, the NIH budget is, I don't remember, well over 30 billion a year. If you were to devote 350 million into women's health, that would generate 14 billion in our economy.

And it's not just that there's an economic incentive, it's that there are so many. There are so many sex specific differences in how diseases impact males and females. 80 percent of the people in the U. S. who have autoimmune disease are women. 80 percent of the people who have osteoporosis are women.

Women are four times more likely to have heart disease after menopause. There are so many things that if we could, if we could understand them, it would make a huge impact in quality of life and health. health consequences and outcomes for half the population. It's just, it's a no brainer at this point.

We just need to do it.

It's the right thing to do. And even if your heart's not in the right place, just think about the economic impact. So I'm always Machiavellian about these types of things. For me, personal, personally, it's also a heart matter. People are just not there. All right, but let's give them

the economic facts.

Yeah, the economic argument is deeply compelling. It's really dramatic when you start to, to dig into the numbers. Yes,

absolutely. And there's a few things that we can already do today if we so choose in order, if you, for example, mentioned heart disease and the likelihood how many more, many fold goes up after menopause.

Let's talk about hormone replacement therapy. Is this something women should be better informed about?

Oh, I certainly think that, yes our education around this particular issue is it's non existent, really. I think we're fortunate. And again, the message is positive that there's a lot more attention being paid in this space.

There's a lot more dialogue in the public in the, Public sector about menopause and ways to treat menopause and HRT is obviously the frontline treatment that we have to mitigate the symptoms of menopause and H hormone replacement therapy or HRT has, I think, gotten a really, it's been maligned.

And this. There have been many studies since then that have shown with tens of thousands of data points on women that that HRT, assuming you don't have any underlying health risks, that would, that would suggest you shouldn't take HRT. But for most women, HRT really is the best Band Aid.

We have to mitigate those health consequences of menopause now, I should say, and it's really important to understand for your audience that I am not a medical doctor. I'm a PhD scientist. And so I do not give medical advice. But what I can tell you is what I think about the data. And I can tell you what I know about the biology.

And so when we think about hormone replacement therapy what is it exactly? It's it's basically trying to add back some of the beneficial chemicals that your ovaries make that are important for general health. And so most people have heard of estrogen, which is one of the, it's the major component of HRT.

Most HRT also includes some form of progesterone or progestin which is another steroid hormone that most people are familiar with that does a lot of different things. And some HRT will include a low dose testosterone. But, the reason that it's important It is because your ovaries are making not just things that are important for fertility and not just, it's not just about the eggs.

Your ovaries also make this whole cocktail of chemicals that are important for signaling to every tissue in your body. And that sort of cocktail of chemicals or hormones. It's like an orchestra, and it's it signals to your brain, it signals to your bone, it signals to your heart and when your ovaries stop functioning at menopause, they stop producing all of these hormones, and so HRT is designed to try and add some of that back to mimic those positive health benefits. And if I'm going into too much detail, just stop me. Not at all. I love it. I think unfortunately the way that HRT is administered, at least in the U.

S. and I think in most other countries it's administered a little bit like a sledgehammer. There's only a few doses available and a lot of women take HRT and maybe it's the wrong dose or, maybe it's the wrong, set of components in the HRT, but they experience side effects and then they stop taking it.

And this is really a place where individualized treatment and personalized care is going to become really important. Because if you think about, before menopause, if you think about how your reproductive. organs are functioning and particularly your ovaries are functioning normally. There's this incredibly complex cycle, right?

Our monthly menstrual cycle is characterized by this beautiful symphony of different hormones that change over the period of your cycle in different directions, right? Estrogen goes like this. Progesterone goes like this. And there's 10 other hormones that change in different ways. So it's this incredibly complex, very dynamic pattern.

And if you don't get the right amounts and if If you hit the system over the head with a giant bolus of hormones that maybe don't quite match what you personally need if you're up here, but what you really need is down here, then that will lead to side effects. So I think there's a lot of opportunity right now today.

to to personalize and to think about how we administer HRT to women. I also think it's important to say when we're talking about HRT that it is not for everyone. And that is a conversation that a woman needs to have with her physician. There are some very important things that would contraindicate taking HRT.

So there's a lot of, there's things that in your health history or in your genetic background might make it might not make it the right thing for you to do. And it's really important that that any kind of discussions about HRT are really had with a medical doctor who specializes in these things.

Absolutely. Thank you for pointing that out, Jennifer. And I would like to know your perspective on bioidentical hormone versus, HRT, the conventional.

Yeah, it's funny. It's such a strange word bioidentical. All of the hormones that are in HRT are Bioidentical. I think it's just a question of whether the hormones are in the HRT are manufactured by a pharmaceutical company or whether they're compounded in a compounding pharmacy.

And I think when you're. Doing compounding you can play around more with the levels. You can also potentially put more stuff in there. So more than just those canonical three that we talked about so there's lots of different forms of estrogen. For example, there's lots of different forms of progesterone.

There are other kinds of hormones like D. H. E. A. And other things like that you could potentially put in there. So when people talk about bioidentical, they're really talking about compounded hormones. And unfortunately, in the US, at least compounding pharmacies aren't regulated. And so I think there's a huge spectrum of quality.

And and there's just a lot of variability that you don't get when you're talking about. Standard that's prescribed from a pharmacy that comes from a pharmaceutical company and I'm not arguing for one over the other. It's just that's what it comes down to. And I think that we regulate drugs.

We like to regulate drugs, we have the FDA because we want, there to be some standards around health and safety. And I think that's a good thing. I think there's a huge opportunity right now for Entrepreneurs and companies to think about what goes into H. R. T. And how and when it's administered.

I think that that there's a big opportunity for for innovating a little bit in ways that will hopefully potentially, results in a much better outcome for larger numbers of women. And what I mean by that is that in addition to just having estrogen or progestin, there are a lot of drugs out there that are called CIRMs selective estrogen receptor modulators.

And what a CIRM is, essentially, it's something that acts like an estrogen or or, any steroid hormone that can selectively activate basically a signal like estrogen, but only to certain tissues, right? So can be selective for different receptors and. Feel like I'm starting to talk a little bit too sciencey here, but not at all, but there, there's just a lot of opportunity out there in terms of thinking about what goes into HRT and how we administer it.

And I'm a, I don't, I, I. I, I think that the debate around bioidentical or not is a red herring because it's really more about whether you're getting, what the purity and the quality and the standards are around the, whatever the compound is that you're getting.

And I think, I think I always tend to err on the side of safety. I think it's really important that we collect data in double blind studies for all of these things, and that's what we use as our guide for what works and what doesn't work and that we, we defer to all of the regulatory bodies that we have set up to help us understand what's safe.

Does that

make sense? Yes, it makes sense. Safety first. Absolutely. And no worry here about getting too sciency. I love that. And I know the audience is also all over it. Okay. I actually would like to get even a little more sciency. And one of the posts on your website, it was actually talk. I think it was a guest who talked about the use of.

Antifibrotic drugs, and also the harvesting of high quality you need to educate me on this

oocytes. Oocytes? Oocytes is just another word for egg. Ah. That's the science y term for eggs.

Ah, yeah so basically using these antifibrotic drugs And using these eggs to extend the reproductive lifespan and women, what is

that?

Yeah if we step back and just think about what is aging in the ovary? What does it look like? It truly is just this decline in the number and the quality of eggs. Or oocytes, if you want to sound, science y. So over time, and there's this, there's a chart that we all know, which is like over time, the number of eggs and also the quality of eggs goes like this.

And when you get to the bottom of that curve, this is where menopause is. And so there's something about we don't really understand why, but there's something about running out of eggs that causes the ovary to stop functioning. And so if you think about it from the numbers perspective female humans are born with all the eggs they'll ever have which is really in stark contrast to what happens in the male system where men can make millions of sperm every day all the way up until they die.

Now they're not always, they're not going to be the same quality and maybe the numbers will go down a little bit as they get older, but But they can make sperm new sperm after, after they reach adulthood. We cannot make new eggs. When I was in my mother's womb at around 26 weeks of gestation, I had 7 million 6 or 7 million eggs in my ovaries.

By the time I was born, that 1 million. By the time I went through puberty, which is, arguably the first time I might ever want to use my ovaries, but probably long after that by the time I went through puberty that number had dropped to about 350, 000, give or take, and then, and all of these numbers are obviously on average, and then once I started cycling I, Lost and do lose about a thousand eggs per month.

And so you just, however many you started with, you just go through these declines and then at some point, or somewhere between 40 and 54, you run out of aches and your ovaries stop working and you go through menopause. So when you

losing eggs, what exactly does that mean?

Every.

Every month essentially your your cycle starts to rec it recruits about a thousand eggs to start developing. And only one of those will get ovulated, or, if you're gonna sometimes two get out, but. Only one gets ovulated. And those other 999 that were recruited and started to grow, they they basically die and are resorbed through atresia.

And I think many women don't understand that, and they also think that if they're taking, for example birth control, that they're somehow preserving their ovarian reserve, they're, like, saving up their eggs. But actually just because you don't ovulate that one, You still have the 999 that are dying.

How that, how and why that happens, we don't understand. But in addition to just the numbers game, the quality of the eggs declines with age too. And if you think about it, it's crazy that it even works at all. That we can store our eggs for. 30 years. And then, in a pristine, they have to be maintained in a pretty pristine state to be able to generate a new human.

But they're stored for, decades before they're used. And and so over time, the quality of those stored eggs goes down. And so what we know is that if you can if you can extend if you can push out, if you can change that number of eggs that are present in the ovary.

If you can make it a little bit bigger a little bit later, that's one strategy, that's one strategy we could imagine might push out. Reproductive aging. So the, I think that the research that you're referring to comes from one of our center members and also one of our grantees. We haven't talked about that yet, but someone, we gave a scientist, we gave a grant to, to study reproductive aging.

And what she found is that over time, with age, that the environment around the egg, right? So there's the egg itself, which is mostly just sitting there, quiescent not doing much, but the environment, it's the environment around the egg that's really changing. And so what she showed is that the, both the micro environment around the egg and also the macro environments of the ovaries themselves with age, that the mechanical properties of the ovaries, like literally how stiff it is.

changes. So it gets stiffer and stiffer with age and becomes more fibrotic meaning that it, fibrosis is this thing that happens after injury and also with age where the tissue becomes stiffer and it gets It's, it changes like the biomechanical properties and in this case what they're thinking is that because they discovered that, the ovaries become more stiff with age, that maybe if they use anti fibrotic drugs, that could be one way to reverse some of those some of those age related changes and possibly improve ovarian function.

But that's what they're testing now.

Understood. Yeah. So for women, let's say in their 30s or 40s, who would like to, take care of their reproductive health and also potentially extend their reproductive span, are, is there anything they can do? that you can recommend?

Yeah, again I'm not a doctor, so I don't make any health recommendations.

I, I think things that improve aging in the rest of the body certainly have been shown to improve aging in the reproductive system. And the very best, the most incredible treatments that we have for age related decline are Diet and exercise. And I know people don't want to hear that. But truly, if you were to do a clinical trial, a controlled clinical trial of where you were testing any anti aging drug that we think about any of them against just diet and exercise will win by orders of magnitude.

Optimizing, women's health. One of the things that irritates me so much about the way we treat women's health is that we relegate it to a sub, like a niche subcategory of medicine, and we tend to treat women by their organ systems, right? Like we focus on, Thyroid or uterus or whatever, we break it down by organ system rather than thinking about a woman's body as a functioning whole, as a functioning machine where every single part of the machine needs to work synchronously and each part needs to be optimized, right?

And if one part is out of whack, then that will by definition impact everything else. And I think diet and exercise are one of the ways that you can really impact the whole system at the same time. That's, it's not very satisfying, but that truly is what I would recommend.

I'm with you wholeheartedly there, Jennifer. And one more question that I have is with regards to women and childbearing. Now, does a woman put herself more at risk when she doesn't have any children at all? And another follow up question to that, does a woman put herself more at risk when she has, let's say, more than three or four children?

I'm not sure that we have definitive data To say I think the answer to the first question is no. I don't think that you put yourself at risk by not having children. And in fact, there are some studies that I'm aware of that that. They're really looking at having a child, the age at which you have a child as a correlate for reproductive span.

So the later, if you have children, the later you're able to have a child the better that is for you in terms of, your Your relative risk of dying later. So it basically positively correlates with longevity. But again, if you can have a child later that kind of by definition means that your reproductive span is longer.

So they're interchangeable in that sense. There are some studies that looked at the. The number of Children and I think it's actually a positive thing, not a negative thing. Although at the end of the day, I would say having a child requires more than functional ovaries. It also requires a lot in terms of your uterus functioning properly and your muscles and all these things and, I imagine that at some point, the positive benefits would be outweighed by some negative consequence of, wear and tear. But but I think that goes beyond three or four. Yes.

Yes. Just imagining some women still today, especially in times gone by who would have 10,

11, 12. Yeah. I imagine that at some point, wear and tear kind of outweighs whatever we're talking about in terms of reproductive span, but I don't know that those, I'm not familiar with those studies, so I can't really say I'm,

I'm just absolutely amazed.

And I bow down to the strength the physical and the psychological. I agree. I love these women. It's incredible. Yeah. I'd like to know from you, Jennifer, is there anything you personally do just to tie this wonderful conversation up? Is there anything you personally do to enhance your wellbeing as a human being, as a woman?

Share with us. Yeah, I, again, it's going to sound really boring and stayed, but I make sure that I get enough sleep. I get a massage every two weeks. I go to yoga. I, I exercise regularly and I mix it up. I don't just do the same thing all the time. I just came back from a trip to London where I was walking something like 10 miles every day.

the city and I don't typically have time to walk 10 miles every day, but I really felt like my body benefited from just having, that sort of different. So it's just mixing it up in terms of what I'm doing in terms of physical activity. But I do think a lot about what I put into my body.

And I, I take time off and, I try as much as possible to take care of myself and I listen to my body. I think that many people get caught up in following whatever prescription, whatever list of things someone tells them to do. And at the end of the day, we really are very different at the level of individuals.

And so I think it's most important that you listen to your own body and that you follow, you follow what feels good for you. That, that would be my advice.

Thank you for sharing that, Jennifer. And for people in the audience who would like to learn more about your work yourself or who would like to connect, how can

they do yeah, I'm on Twitter and I'm also on LinkedIn. I have a lab website, which is garrisonlab. com, but I think for this audience, they probably are going to be most interested in the Global Consortium for Reproductive Longevity and Equality, which is a mouthful. Call it the G. C. R. L. E. This is the nonprofit that I co founded and direct, which is really trying to stimulate research in the space and build out the ecosystem around reproductive longevity.

And so we fund grants to scientists. But we also are spending a lot of time trying to build out the network of people who have an interest in the space. So that means clinicians. It means funders. It means people like you who can spread the word and be ambassadors about what we're doing. It means educators.

It really means anyone who has an interest. And so if that's you in the audience, then please, we want you to be part of it. That website is GCRLE. org.

Fantastic. I'll make sure to put all of this also in the show notes. Jennifer, do you also have memberships for people who would like to actively join and support?

You don't need to join anything. We do have a network and we certainly do have a lot of meetings. We're developing this knowledge hub, which is meant to be an educational tool for women and also for doctors. Certainly, we're always looking for philanthropic donations simply because as much money as we can raise, that's the money that we can give away to scientists to really study these questions.

And like I said, what we fund in science dictates what we know. And so I think from my perspective, there's not nearly enough science funding happening in this space. And so we just decided to. To give away the grants ourselves until and at the same time, we're also, doing a lot of lobbying to increase not just private private funding, but also public funding for the science and really what we.

What we need more than anything besides funding is really increased public engagement supporting the science and the scientists. I think they're the heroes of this field and as big as this issue is globally, I think it should be, this should be something we're talking about over dinner everywhere, everyone and to the extent that we can have ambassadors and people just talking.

About, talking about what happens in women's bodies and then talking about how little research and how little funding there is for it. I think those conversations are what's going to help push things forward faster. That's what we're hoping for. Yes, those

are this is vastly important.

And as you said, it's half of the population. Guess what? The other half of the population is directly influenced by the well being. Of the first half of the population. Everyone has a mother. A lot of people have sisters. Best friends. Women friends. Anyhow, it benefits us all. That's really what I think is so important about this.

To all get on the same page here. We're all in this together. Thank you so much for all the work you're doing as a scientist, also with regards to lobbying and an activist, a spokesperson for this. It was such a pleasure to connect with you, Jennifer. Thank

you so much. This was a great conversation. I really appreciate it.