Delaying Menopause And Slowing OVARIAN AGING For Longevity with Dr. Jennifer Garrison

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 want to get top tips, insights, and strategies for optimizing your life, your health, and longevity, grab my weekly newsletter by going to llinsider.com. Today's returning guest is Dr. Jennifer Garrison. Jennifer is a world-renowned scientist who has won numerous awards for her research on aging and brain science and is a passionate advocate for women's health. Her science focuses on female reproductive aging, and she is a faculty director of the Global Consortium for Reproductive Longevity and Equality. Jennifer is an assistant professor at the Buck Institute for Research in Aging and holds appointments at the University of California, San Francisco, UCF. And the University of Southern California. Jennifer, it's my absolute pleasure to have you back on today. Thank you so much for coming.

Thank you for having me back. I'm really honored to be back again.

The honor's all mine. Jennifer, for those who may have missed our previous conversation, can you give a brief background on what your lab are working on around women's health and what you're currently focused on?

Sure. Yes. I wear a couple of different hats and I do run a research lab at the Buck Institute. And the Buck is, for those of you who don't know it, we're located just north of San Francisco. It's a research institute that's wholly devoted to understanding mechanisms of aging. And the logic there is that many of the chronic diseases of the modern world, things like cancer, diabetes, neurodegenerative diseases, these are all the major risk factors for these diseases are your age. So the idea is that if we can understand basic mechanisms of aging, those underlying mechanisms and target those, that we would then be targeting all of those diseases simultaneously and reducing overall disease risk. So as a neuroscientist, what my lab studies is how the brain communicates with the rest of the body through chemical signals that are long-range communication tools. So we're not talking about synapses and wired circuits. We're talking about this kind of chemical communication.. And what we're interested in is how changes in the neural circuits in the brain that release these chemicals and sense these chemicals, how changes with age can essentially lead to systemic aging. And we spend a lot of time thinking about how the conversation, the chemical conversation between brain and ovaries and other reproductive organs changes with age and how that might be some of the causal factors that influence female reproductive aging.

Just for those perhaps unfamiliar, what is the challenge around reproductive aging for women? What are some of the biggest issues?

Well, there's, there's a lot. Major challenge is that we don't have a lot of data. So when I talk about female reproductive aging, what I'm talking about is the fact that ovaries age prematurely. So compared to aging in the rest of the body, a female human's ovaries are aging at about 2.5 times the rate of the rest of the tissue. And so what that means practically is that when a female human is, you know, in late 20s, early 30s, when most tissues are functioning at peak performance, ovaries are already showing overt signs of aging. And that premature decline essentially manifests in a whole host of different ways. I think most people are familiar with the downstream consequences with respect to fertility reproductive function. So aging in the ovaries leads to things like birth defects and miscarriages and infertility. But on the other side, setting aside fertility, ovaries also produce this huge cocktail of hormones that are really important for general health. And those hormones, some of them are these long-range communication signals that talk to the brain. And when ovaries stop functioning at menopause, and stop releasing these hormones, that has a real dramatic impact on general health. So it leads to things like increased risk of cardiovascular disease, increased risk of stroke, increased risk of osteoporosis, cognitive decline, and a whole host of other things. So when I think about female reproductive aging, my goal is really to try to understand what causes that premature aging in ovaries. We don't know like what actually sets it in motion as a way to have therapeutic intervention points, right? The ways that we treat infertility and menopause right now, a lot of them are just band-aids. They're great band-aids, IVF, HRT, they're great band-aids, but they're not really addressing the underlying causes. And if we could get at those underlying causes, then we could potentially give women a lot more agency over how and when they decide to have children, how healthy those eggs are when they want to use them, and also just restoring health in their later years. I think those are the things that we care about.

Also, I liked from our previous conversation what we were talking about for women to think about economic equality for women, because it takes the pressure off making certain career choices earlier on. You know, I came from previously working in investment banking. You know, how many female partners are there? How many female managing directors are there? Right? There's this attrition that happens and just allowing women to actually not have to make family choices earlier and build their career out and have more economic success and equality. There's so many beautiful benefits of getting to the bottom of this and understanding it. So I think it's such an exciting area, Jennifer, and I'm so happy that you are focused on this and helping to change women's lives in the future. So thank you for sharing that. I wanna ask you next, Jennifer, your why. Why is this so important to you? Why are you so passionate about supporting breakthrough discoveries for women's health?

Let's be honest, part of it is probably selfish. I do happen to have a pair of ovaries and I'm not super excited about all of the things that are gonna happen to me when they stop working. But setting that aside, in addition to my research lab at the Buck Institute, a few years ago, we started this global consortium. And we call it the Global Consortium for Reproductive Longevity and Equality, GCRL. It's a big mouthful, but we think that all of those words are important. And so this is truly a global effort to build out the ecosystem around this area of research. And our mission is to facilitate and also accelerate translating those discoveries that are made in the research lab into women's hands faster. Products, therapies, diagnostics, biomarkers. And so how we're approaching that now is to fund basic science research, to actually give grants to scientists all over the world, and also to build resources to help them move things into the clinic faster. And the reason that we chose to focus there is because there's been a real lack of funding and also a lack of data in the space. And you touched on the word equality. It really is, I think, an issue of equality, both financial and societal. The fact that women go through this reproductive decline in the middle of their lives truly does influence every aspect of their lives as adults, whether they want to have biological children or not. Every decision that I had to make as an adult about my career, about family planning, about my health, there's this ticking biological clock in the background always. And men simply don't have that. There's also the fact that when women start to go through perimenopause, as they're approaching the menopausal transition, there's a whole host of vasomotor symptoms that manifest as things like hot flashes and brain fog that dramatically impact a woman's ability to do her job, to function in her daily life. And again, men don't have to deal with these things. So that's why we think about this as an issue of equality. I genuinely think that this is the most important thing that I could be focusing my time and attention on right now, because it's not an unsolvable problem. Understanding where and when and how and why ovaries start to age prematurely. This is a knowable piece of information. It's probably a complicated answer. It's probably a constellation of cues and timers that maybe happen at different times. But again, these are answerable questions. And if we can discover these things by doing the research, then that opens up a whole world of potential interventions and therapies that might increase a woman's ability to have a healthy baby at 40. There's just so many things that if we can understand what's happening, there's so many positive benefits that will come from that for literally half the population. Literally half the population. It's not rocket science. These are knowable questions. And so we really just have to do the work. There's been a total lack of funding in the space. And as a scientist, I can't work on a research question if I don't have a grant to fund my lab. So the grants that I get to fund my lab are usually about specific projects. And if I don't have a grant to fund the research that I want to do on female reproductive aging, then I cannot work on it. So giving out money to scientists and trying as much as possible to bring as many creative scientists all over the world into this space to focus their considerable intellects on this problem is something that I think is achievable. And if we do it, it will have an incredible impact on the world.

Beautifully said. For people listening, I think many people are more familiar with the business space and investors, but scientific funding is very specific. So can we take a bit of a deep dive into scientific funding?

How does it actually work? Yeah, I would love to. And I'm always surprised at how even my family, even my friends, people who have known me for decades, who watched me through all my training, have watched me open my lab and do my research, even they don't really understand day to day what my world looks like. So I really appreciate you asking me that question. So scientific research happens on the academic side. It happens at universities and at independent research institutes all over the world. And so universities, you mentioned USC and UCSF, everyone's familiar with universities. Then independent research institutes like the Buck Institute. Other examples might be the Broad, which is in Boston at MIT, the Salk Institute in San Diego, the Max Planck Institutes in Germany. These are all independent research institutes that do academic research, have educational programs, but they're really focused just on science. It's not a whole university. But in general, the way that labs are set up is the same across institutions and across the world. And so there's a lab head. I'll use my lab as an example. So I head the Garrison Lab, literally, at the Buck Institute. And there are 24 labs at the Buck Institute, and each one is headed by a different professor. And we are all working on scientific research questions that we personally think are interesting and that we have the training and the expertise to address. No one is telling me what to work on. That is entirely my choice. However, the sticking point is that I have to be able to fund my research. So when I open my lab at UCSF or at the Buck Institute, I have to bring in all the funding for it. So that means I have to fund my salary. Everyone who works for me, their salaries and benefits, all of the money for the supplies, for the equipment, for the reagents, all of that, I have to find that funding. Now, most universities and institutes will provide some portion of my salary, the lab head salary, in exchange for, you know, some service. So for example, if I teach graduate students, some tiny portion of my salary might be covered by that. If I sit on committees and I do other service for the institution, that will cover some portion of my salary. But just in general, I have to go out. It's almost like when I opened my lab, I was given space. And so that's the other benefit of the institution is that they give you space that comes along with a lot of administrative support. So they have a grants department that helps you submit grants. They have an HR department that helps take care of onboarding and offboarding and handling your employees. They have a finance department that pays the bills and things like that. In our case, they have a wonderful facilities team who maintains the physical space. So those are the benefits of being there, but to actually fund my lab, I have to bring in all that money. And so the way that I do that is I apply for grants.

In essence, if somebody's trying to kind of understand from the outset, from a more business perspective, it's almost like you join an accelerator, right? Like you're a startup with your own idea, but you have to find the external funding all by yourself. So you're given the space, you're given certain support systems, but it's all otherwise up to you to make it happen.

Exactly. You've got the framework to have employees. It's almost like you're a small business. It's like I'm a small business and I have to go out and find all the funding. So if you take who's in a research lab, if you take my lab as an example, and this is true across the board, There's me, and I'm not actually in the lab at the bench most of the time doing experiments. I certainly train people, but most of what I'm doing is managing, getting the money, you know, having my trainees bring me data and helping them work through what the next experiment should be. So really thinking it through. But in my lab, this is the way that research labs work. There's several different types of employees. So starting from the entry level, we have employees who are there to really support everyone else. So they do things like order supplies and make solutions and do really basic stuff. Those roles might be filled by people who only have undergraduate degrees or who are even undergraduates in training who are doing internships or come in for part-time jobs. Then we have a lab manager who would be someone who's more just keeping an eye on everything, making sure that things are working properly, making sure that everyone has what they need, making sure the equipment is serviced, things like that. And then we have graduate students. So those would be either students who are working on their master's degrees or students who are working on their PhDs. And so the way that you get a PhD in science is that you work in a lab on a research project and you publish papers. PhD doesn't require much coursework. It really is hands-on, taking a project, making it your own, and carrying it through all the way from start to finish until publication. And that usually takes somewhere between 3 and 5 years. So I have PhD students in my lab who are all working on their own independent projects. And all of this is under the umbrella of my research program. So they're all sort of based around ideas that I have. And then I work with my trainees to come up with projects that they think are interesting that also fit into our research umbrella. And then I have postdoctoral fellows. So once you finish your PhD, if you want to continue down the path of becoming either an industry or an academic researcher, you go to a different lab, potentially working on like completely different things, and you do another project that could take anywhere from 2 to 5 years where you take it from start to finish. And this really broadens the training. So it broadens your scientific knowledge, it broadens your background. So postdoctoral fellows are people who already have their PhDs from somewhere else. Who've come to get even more training. And so they're more senior, they're more experienced, they cost more. And then sometimes we have like senior research fellows who would be people who have finished their postdocs, but want to continue working at the bench, doing experiments rather than going on to become a PI or lead a group. That's who's— and, you know, undergraduate interns as well. Those are the people that are working in my lab.

So they're all conducting different parts of research in collaboration with you and you're helping them and guiding them, but you're busy focusing on funding and organizing that they can actually be paid.

Exactly. Yeah. So I meet with people once a week. We talk through their data. We talk about what they should do next. We have a lab meeting every week where everyone comes together and talks about what they're doing so that as a group, we can help people troubleshoot, you know, science, 90% of science is an experiment didn't work. That's actually what I tell my PhD students. Your job is to learn how to fail repeatedly over and over and over again and not get discouraged by it because that's how science works. Most of the things we try, most of the things we think of are not quite right and you just have to keep iterating. Perseverance is the key trait that you need to be a successful scientist. So there's different kinds of funding. So as trainees, PhD students, and postdocs can apply for fellowships. And so they can actually apply for their own grants. I do try to help my trainees apply for those, but the funding rates for those can be pretty small. They're very competitive. And funding rates for a postdoctoral fellowship, for example, which would cover a salary, they're very prestigious awards usually, and they tend to be in the 5 to 10% funding range, meaning that 5 to 10% of the incredibly qualified people who apply for them will actually get the awards. While I encourage my students and postdocs to apply for those, we don't count on them because, you know, it's not very probable. But when they do get it, it's wonderful because it really helps them establish a track record of being able to get independent funding, which is important for being able to get a job afterwards. But most of what happens in science funding is that I apply for grants either from governmental bodies. So in the US, that would be like the National Institutes of Health or the National Science Foundation or the National Academy of Medicine. And in Europe, there are similar governmental funding bodies or from private foundations. And I'm sure everyone is familiar with places like the Gates Foundation or the American Heart Association. There's many, many different private foundations that give grants to scientists and they tend to focus on one disease or one topic. You know, there's the Cystic Fibrosis Foundation or the Leukemia Lymphoma Foundation. And they're really focused in on awarding money to study one particular disease or one particular problem. At the NIH and at these governmental funding bodies, the grants are awarded by different institutes. Are you following me?

I'm following you 100%.

I don't want to get too far in the weeds, but I really want people to know how this works. It's hard to understand why there's a problem with science funding without understanding how it works. There's no question that lack of funding, you know, just the levels of funding overall is an issue, but there's a much more fundamental problem. Even if we had tons of money, there's actually a much more fundamental problem with science funding right now, which is that the grants that get funded, like if I want to get a grant from the NIH, generally speaking, the most common grant funding mechanisms, there's, you know, NIH has many different kinds of grants that give away. And they're all different amounts of time and they're all different amounts of money. So some are very small for just a few years, some are bigger for more years, but for all of them, the grants that are awarded are really addressing what I would say is incremental science. To get a grant from NIH, generally speaking, I have to submit an application that is extremely well thought out, which is good. Extremely well detailed in terms of like exactly what steps I'm gonna take to address the question I'm interested in, which is all good, but it also needs to have a huge amount of preliminary data. So almost like the project has already been done and there's just a little bit more to do to tie it all up in a neat bow and publish it. So the amount of preliminary data and the amount of detail in terms of exactly what you're gonna do is required to get funding. And what that does is it selects for science that is incredibly incremental. Like it's just a little, it's just learning something just a little bit more than we already know. Not big blue sky risk-taking stuff. It really constrains what I can do. And unfortunately, science doesn't work like this usually. Usually you do the first one or two things and the results are not what you thought they were going to be. And so many times what should happen is that you should take that information that you've just gotten and pivot and go in a different direction. However, in order to get grants renewed from the NIH, you have to show progress on the aims that you wrote about.

From the original one.

Okay.

So it doesn't take into account, like you were saying, the perseverance is really important cuz 90% of the ideas are gonna be different.

Every year you write a progress report, you can, in the progress reports say, okay, I want to change the direction and change the aims. But every step of this grant writing and grant maintaining process requires a huge amount of energy to do the administrative component, to write the thing, to say like, I need to change the aims and here's all the reasons why. Every single bit of it takes so much time and effort. And to give you a sense, like my research lab is not huge. I have 8 to 10 people, depending on whether or not you count the undergraduate interns. And I have 3 postdoctoral fellows and 3 fantastic PhD students and a couple of technicians who are people who have graduated from college and still trying to decide what they want to do with their lives, whether they want to go get a PhD or an MD, or whether they want to do something else. So it's like a nice transitional period. And to support my lab, I have 8 different grants. And they're all for different amounts of money and different lengths of time. And so there's this patchwork of funding that supports my lab. And at any given time, I have to look at the whole picture and decide, you know, okay, there's going to be a— in 2 years, there's going to be a gap because this grant ends. I never know whether it'll get renewed, and some of them are not renewable. And so I need to start applying for funding now to fill that gap because it also takes about a year from the time you apply NIH to actually know whether or not you're going to get the funding. And so I'm constantly writing grants to try to fill these gaps. And I spend a huge amount of time on writing grants because most grants are not funded. So there's the time that you waste trying to fit whatever it is that you're doing into whatever the framework is for the grants that people want to fund. You have to kind of take what you're doing and make it fit in this little box. And then you have to do that over and over and over again. So it's really like a time-wasting process. And I will say that writing grants, thinking through what you're doing, coming up with new ideas, the process itself is really valuable, but only if you spend less than 30% of your time doing it. Especially many young lab heads will spend upwards of 70, 80% of their time just writing grants because they're terrified that they won't be able to get funding for their labs. It's a really inefficient process and it really excludes the kind of science that we want people to do. As a lab head, as a scientist who's been trained, you know, I have 20+ years of training. Like I know more about my research and what direction it should take than anyone else. So giving scientists the freedom and saying, we trust you to take your work in whatever direction it needs to go. So funding like the lab instead of the project would be a huge leap forward. That would make a huge difference.

What does that mean? What would that look like?

Yeah. So, um, there's a couple of examples of this that exist in the world and they are by far the most successful examples of science funding that I personally know of. And I define success as these are the labs where the big discoveries are coming from. These are the labs that ends up winning Nobel Prizes. So in the US, there's an organization called HHMI, which is the Howard Hughes Medical Institute. And it's a very unusual funding mechanism that's been around for decades. It literally is Howard Hughes's legacy, what he left to the world. And what they do is they're basically driving science discovery by cultivating this community of scientists and giving them the resources they need to make the breakthroughs. So what they do is they fund researchers at their home institutions. So for example, you can become an HHMI investigator anywhere in the US. So you can be at Yale, you can be at UCSF, you can be at any institution. And they also have international grants. But once you become an investigator of HHMI, what happens is you sort of become like a visiting scientist in your own university. So the university no longer pays you. You're an HHMI employee, but you still have your lab and you are embedded in whatever university that you work at. And what they do is they fund the entire lab. So they fund the investigator, they don't fund a project, and they give the investigator enough money to run their lab, to pay their people, to buy equipment, to buy supplies, not a huge lab. So they can still apply for more grants and build their lab even bigger, but they give them enough money so that they can run their lab without having to apply for other grants. And they're not telling them what to work on. They're saying, we see what you've been doing. We trust you. We think what you're doing is amazing. And you take your research in whatever direction you want to go. And that really frees people up to be creative. It frees them up to take risks and it frees them up to follow the science and the results where they take them. So over the last, I don't know how many decades, I think it's been at least 30, probably 40 years that HHMI has been around. They funded something like 250 researchers over that time. And of those, 34 are Nobel Prize winners. That's a huge percentage. And if you look at the most impactful research that's being published, you know, the papers that are coming out, particularly from investigators in the US, Many of them are coming from these labs because they have that freedom. The other piece of the HHMI funding that it's funding this science and not a particular project. The other piece that's really innovative and that makes a huge difference is that they fund these researchers for 7 years. So it's renewable and they have 7-year runway before they go up for renewal. And if for some reason they don't get renewed, which can happen, there's a 2-year wind-down period. And so it's really 9 years of funding, which is a decent runway to get something really impactful done. Most grants are 2 to 5 years at best, and sometimes they're renewable, but again, you don't know if you're gonna get renewed until you get right up to the end of it. So there's no insurance policy that you'll have that money going forward. And so what happens is you get a 2-year grant, you do whatever project you said you were gonna do on whatever topic.. And at the end of those 2 years, if that funding ends, then you have to pivot and start working on something else. And so this kind of like constantly reworking the direction of your work and this kind of disjointed funding, it's really detrimental to progress. What we need is funding for the science and not a particular project. And also this kind of sustainability, this insurance policy, that those are the things that I think foster the kind of innovation that we want to see.

What type of funding is going into something like that?

Yeah, they have a little over 60 investigators right now in the US and their budget last year for that was $678 million. It's a lot, right? I mean, it is a lot. It costs a lot to run a lab. It's at least a few million a year for each investigator. And you know, they do fund things like equipment, but they really facilitate every aspect of what a researcher needs. They really do. And it's amazing. And so that would be like, the ultimate gold standard. And so where we are here and where those very lucky HHMI investigators are, how do we bridge that gap in between? Because obviously, you know, giving everyone HHMI level funding isn't really practical. So from my perspective, right, in 2020, we started the GCRL. We are giving away grants to scientists. We gave away our first grants in 2020 to 23 scientists all over the world. They're 2-year grants.. And so I've been thinking a lot about like, how can we take what we're doing and at least try to instill some of the sustainability so that we can foster these breakthrough discoveries that we want people to be making. So we skipped a year of funding because of COVID because so many people had to close their labs down, but we're literally just about to give away the second round of funding. And just to give you a sense, it's as much money as I can raise philanthropically, but around $7 or $7.5 million for these first two rounds, each one. I'm so proud of what we've done in terms of being able to stimulate the field. We had the first international meeting last June where we went from a handful of people working in this area to over 100 people who, a lot of them are coming from outside, from different areas of science, who think this is an interesting problem. And now that there's funding available, are actually trying to work on it, which is spectacular. And we had the second International Reproductive Aging Conference that literally ended 2 days ago. And again, there's so much interest in the space. It's really that we just need the resources. So I'm thinking through what we want to do going forward with each subsequent round of funding. My vision is that we would still have a new call for grants that we're always going to be trying to pull in new people and fund new scientists to work in the space. And also specifically that we'll always be funding postdoctoral researchers. So we fund fellowships because we want to grow the next generation of leaders in this space. So we'll always have that track where we're giving away new grants to scientists all over the world. But what I'd like to do is to have a second parallel track that existing grantees or former grantees can apply to that would give them a little bit of this sustainability. Right. We have them write projects, but if they run into problems or if they get results that tell them to take a left turn, we give them the freedom to follow the science wherever it takes them. We don't tell them they have to work on this thing they told us they were going to do. As long as they're making progress and as long as it's related to discovering those underlying mechanisms of reproductive aging, we give them carte blanche to do whatever they want. So that piece we've solved. But the sustainability piece is really tricky. So the goal would be to have this track where they could continue to get funding to work on whatever it is they're doing. So that's the vision. And now I need to raise essentially what would amount to an endowment so that we can do that. And so that's what I'm spending most of my time on now is really just trying to raise philanthropic dollars to facilitate that second pot of money because we have an amazing seed funder who's given us so much support to get these first two rounds of grants off the ground and will continue to support us at a certain level. But in order to get to the sustainability track, I'm trying to raise quite a bit of money.

What's the target number you're working towards, Jennifer?

I mean, at a minimum, from my perspective, I think we want to continue with this model for at least 5, hopefully 10 years. And in that timeframe, I expect major discoveries to be made. That might pivot the way we're thinking in 5 or 10 years. It might be that we decide like, hey, the NIH, you know, we spend a lot of time actually now petitioning and lobbying these funding bodies to start to pay attention to this research area. So I hope that that will start to bear fruit and that NIH and NSF and all of these other funding bodies will start to wake up to this as an important area and that they'll start to increase the amount of money they're putting in.. And as they do that, and as the discoveries are made, as the IP is generated, I keep telling people that, you know, this is an amazing area for investment, but there is no IP that's going to give you any therapeutic value that just doesn't exist yet because we haven't done the science. But in 5 or 10 years, as we move towards getting those discoveries, generating that IP, and having these other funders pay attention to the space, I think that we can pivot from doing just basic science to starting to invest in those early-stage companies that might be coming from those researchers that we funded. And then hopefully we'll get some sort of a feed-forward model where we can make it a sustainable funding model as well. But right now, I think the minimum that we need for this is going to be in the $50 million range to really have that minimum 5-year runway. And more than that would be great. That's why I'm calling it an endowment.

That's a great term as well. And this is work that will affect half of the world's population.

So a worthy cause, right? If you take a step back, it actually will impact everyone in the world who's aging because ovaries are so interesting, right? If you think about it, it's like a time machine. Ovaries give us inside of a human, a model for accelerated human aging, right? There's so much interest in the longevity space on trying to find interventions that will extend healthspan lifespan. One of the big elephants in the room is how do we test those longevity interventions? Right now we use animal models or cell-based models, and I think the best animal model we have right now is either a monkey or a dog. But ovaries give us the opportunity to test interventions in a human model, right? You can imagine doing clinical trials for longevity or healthspan interventions that use women in their 30s with really measurable endpoints. Things like pregnant, not pregnant, measuring things like bone density and hormone levels, really not very invasive things to monitor ovarian health, which is then a proxy for aging in the rest of the body. If we can understand why ovaries are aging prematurely, if we can really get at what those mechanisms are, that will tell us something about aging in the rest of the body as well. So this becomes an important thing for not just women, but also men.

Where's the best way to reach out to you or to find out more about exploring potential donations or getting involved in the endowment?

Oh yeah, we have a website. It's gcrl.org, and on there you'll find my contact information, but people are welcome to reach out to me directly. I'm drjennifergarrison@gmail.com, and I'm happy to talk to anyone about this. I think that there's an opportunity for really rethinking how we do science funding. But part of the struggle is just to educate people and help them to understand how it works. Because there's a lot of well-intentioned people who are trying to disrupt science funding. And because they don't understand how it works and the intricacies of like overhead and, you know, we end up paying quite a bit of overhead to the institution, but that's because they take care of all of these other things for us, right? We're paying for the HR and the facilities and all of those things. And a lot of disruptive science funding doesn't pay overhead. And so that becomes a real problem for the lab because if I take a grant that doesn't pay overhead, I still have to pay that overhead out of my other budgets. And so it all comes out in the end. And so grants that don't cover overhead ends up really not being helpful. Anyway, sorry, that's a little bit getting into the weeds, but yeah, you can. Find us on our website, which is a work in progress. I'm also on LinkedIn.

I'm on Twitter. We'll link everything in the show notes for people listening. I would like to talk about also the market size and growth opportunities from people maybe more used to a traditional sort of venture investing model.

So women's health market. So this is all of women's health, not just menopause or fertility, but all of women's health this year is around $42 billion. So that's a huge market opportunity, right? And I think a lot of investors are waking up to that. And of that market, you know, the people who are making up that market, and I should say that's predicted to be around $58 billion by 2030, which in a really terrifying way is not that far away. So it's a huge market to start with and it's growing. And the people who make up that market, about 40% of them are women over 50. And that's also going to continue to grow. So of that $42 billion market, about 38% of it is focused on the menopause space. And so that's $16.1 billion is women who want menopause products and treatments and therapies. And that menopause market is predicted to be about $30 billion by 2030. So it's a huge market. I mean, enormous. But despite that, the menopause market that we have now is really just band-aids. It really is just things that treat symptoms, not causes. That's not to say that we don't need the band-aids, we absolutely do, but we're hoping that we can add in this component of therapeutics and things that really do genuinely change the trajectory of a woman's fertility and of women's health. One of the sad things about the market itself is that only about 5% of the startups that are focused in women's health target menopause, despite the fact that 40% of the women are in that demographic. So I think there's a huge missed opportunity there. And when you think about perimenopause and menopause, more than 80% of women experience symptoms. So they need those band-aids. They really do. And over 40% of women have said that they've considered leaving their jobs because of those vasomotor symptoms. So it's not just like a fluff thing. It's not like they need a face cream to get rid of their wrinkles. These are real genuine problems that industry has an opportunity to address. And I think people are often quoting the statistic that 80% of the healthcare dollars are spent by women in this demographic. That is true. If we step back and look at the funding on the research side, I often show a graphic from the NIH because it's the largest biomedical research funding body in the US. In 2018, the budget was something like $26 billion. It's much bigger now, but of that 15% went to all of women's health, all of women's health. So from conception through death, and of that about $43 million went to reproductive aging in women, which is basically a rounding error. It's not even, it's not even significant. It's less than 0.1%. And now since 2018, we've been monitoring every year and actually the funding has increased steadily. So that's a good trend. But when you look at where we are now, it's still 2% of the budget. So it's going in the right direction, but it's like laughably small when you think about the fact that we're talking about half the population. And when you think about the implications for what this kind of research can do, there's a beautiful organization who put out an amazing report. It's called the WHAM Report, which I highly recommend people to look up. W-H-A-M. They're nonprofit. And they just ask a simple question, which is if we put research funding into women's health, what is the economic benefit? And it was incredible. I'm going to probably misquote this, but it was something like, if you put in $325 million of funding into research on women's health, which isn't very much, right? I mean, we just talked about much bigger numbers. If you put in $325 million, the economic benefit is something like $14 billion, $13 or $14 billion. It's a, it's an enormous benefit. So there's so many compelling reasons to put time and attention and money into this space. There's really no reason not to.

We just need to do it. Jennifer, what are some of the most interesting or promising research being done that you're seeing? 'Cause I think you have a very good overview of what's happening in the space.

Yeah. I mean, I just saw so many incredible talks at this meeting where people are, you know, presenting their unpublished data, like the most recent results, the things that just came off the presses, you know, the day before. I think that there's, There's really exciting work that's being done on many fronts. So again, since we don't know where or what those causal cues are, it's really important to cast a wide net. So there's a lot of really exciting work being done on model development, right? Because we don't have good models for menopause since human females and whales are really the only species that go through menopause. We don't have great animal models. So developing human cell-based models and also better animal models to study these things is really important. So there's a lot of great work going on there. And then in terms of therapeutic targets and discovering what those underlying causes might be, there's a lot of promising cellular targets on the horizon. Things that are both inside the egg itself, so things like mitochondria, oxidative stress, immune sort of stuff, but also thinking about the micro and the macro environments around the egg. Because if you think about it, the egg is mostly quiescent, it's mostly just kind of sitting there. I mean, that's not totally true, but, but the things that are changing drastically are the things around the egg. So that would be the microenvironment in the follicle and in the ovary itself, but then also in terms of like woman as a whole, like in the whole body. And so we're finding a lot of the signatures that we see in aging and the rest of the tissues also operate in ovaries. So there's some really interesting work showing that the mechanical properties of the ovary, like the tissue stiffness, like how biomechanically stiff it is, change with age and how that happens and what that means for function, right? Because actually, if you think about it, every month there's this dynamic physical remodeling that happens and how stiff or not stiff the tissue is really can dramatically impact function. So looking at anti-fibrotic drugs and things like that to kind of reverse some of the fibrosis that we see in the ovary with age. There's so many things. Oh my gosh. How the microbiome interacts. With reproductive aging. I think lots of women don't realize— I didn't realize this until I read the grant application— that your microbiome actually dictates how much circulating estrogen you have in your body. So your body has to make the estrogen, but once it's there, how much is kept in circulation versus how much is excreted is entirely dictated by microbes in your gut. They have enzymes that can modify estrogen that either put it back into the circulation or put it on the path to be excreted.

So that's mind-blowing.

Have they identified which microbes they are? To some extent, yes. And so right away that sounds like a really interesting therapeutic target. We're talking about things at different levels, right? So at that level you still have to make the estrogen. Correct. Or provide the estrogen, right? But again, we don't know where we're gonna find that discovery or those discoveries that really lead us to therapeutics.. And so it's really important that we cast this wide net and we need like an army of creative scientists working on this problem collectively. And we also need them to collaborate and to talk to the clinicians who see the patients. And so we use our grants as kind of a lever to get those groups that don't normally interact to talk to each other. This is what I spend a lot of my time on. And then bringing in the entrepreneurial aspect as well, bringing in the early stage founders and the funders who want to commercialize these things. Putting everyone in the same room so that the entrepreneurial spirit and the creative scientists can basically work together. How we can foster this collaboration sooner is something that I think a lot about. Can you talk a little bit more about that? So, you know, I try to meet people where they are, and one thing that we've always had our eye on is helping our scientists. We provide a lot of resources for them. We built an ovarian biology core facility to help them learn how to work in ovaries if they didn't already. And one of the resources that we provided is a translational advisory board. So this is an advisory board of heavy hitters from biotech, from investment, from pharma, who know how to make drugs, who know how to move things in the clinic, who volunteer their time to look at the science coming out of the grantee labs and out of the center labs to, when they see things that are translatable, to help that move. And, you know, not everything is going to be translatable, and that's okay. That's not the goal. The goal is really when things are there to help the scientists move them. So we have a trusted investor circle where the vision would be to eventually, you know, start an accelerator and fund companies in the space. But right now there just isn't enough IP. Like there literally isn't IP on the therapeutic and the, and there's diagnostics, there's biomarkers, products, and devices certainly. But that's not what we're interested in doing. We're interested in funding those things that are really going to move the needle. So right now we're taking this approach. Where we're putting all of our resources and attention into generating the IP and to giving scientists the tools and the funding they need to do the discovery work. And so for investors, you know, a lot of what I do is I know all the early stage founders and I try to keep in touch with anyone who has an interest in the space. And so for those early stage founders who are working on the diagnostics and the biomarkers and the devices, which are absolutely critical, right? I try to connect them with investors who have an interest in funding those things at that stage. I'm actually leaving on Sunday to go to the Med ChemTech Congress in Paris. It's the first one of its kind, and it's really meant to give early-stage founders in Europe and outside of the US to give them a platform to talk to investors and to pitch their ideas. Because obviously, you know, I'm here in the Bay Area where we sit in this privileged position with Silicon Valley. Right here, but the rest of the world doesn't necessarily have that. And like I said, this is meant to be a global initiative and we really want everyone because there are so many creative, wonderful scientists and entrepreneurs outside of the US who don't necessarily have access to the same resources. So we're trying to level that playing field. But yeah, I think from my perspective, from an investor's point of view, I think the lowest hanging fruit is really to think about the diagnostics. Right. The way that we approach women's health, and when I say we, I mean clinicians, try to tell a woman where she is in her reproductive span trajectory, like, is rudimentary at best. You know, we take temperature, we measure some handful of things that, like hormones, for example, on one particular day when actually it's this fluctuating orchestra of many different things. And you really need to take a much larger snapshot to understand what's going on. So that static snapshot doesn't really help. So there's a huge opportunity to innovate there. I think every woman in the world would pay, and I think insurers would take this up if there was a reliable and accurate way to have a panel that I would say, for example, every year when I go for my pap smear, a panel, a women's health diagnostic panel that would tell me with some accuracy where I am in that reproductive span trajectory? Like, am I here or am I down here? And while that won't change anything, that kind of knowledge would be so powerful for women to take control of their lives really. Because the way that it works now is nobody knows. I'm sitting in the most wealthy area in the world. I have all of the knowledge, right? I mean, I couldn't have any more knowledge about my own body at this point. And I still don't have a good, clear idea of where I am in that trajectory. And until we can change the trajectory, having at least an idea about where you are would be so powerful. And there's many other examples of products that are, you know, potentially really useful and interesting for women who are in this stage of their lives.

And I guess once you have that diagnosis or you know where you are, then there's bound to be then peripheral things that will come from that and optimization opportunities. Et cetera.

Yeah.

So it just opens up the door and the gateway to the next round of innovation that would come out of it as well.

Exactly. It's also worth saying, especially to the men in the audience, that women's health in particular and women's bodies are incredibly complex. I really think that female physiology and female reproductive physiology in particular is the most complex multivariate signature in all of human health. And so this is a place where individualized treatment, you know, what you need and where you are is going to be completely different than what I need and what other individuals need or where you are. And so having, you know, this is a place where personalized medicine is going to become really important. And that also means that there's a huge opportunity for solutions that are not like one size fits all.

And we are at that space of precision medicine. Personalized medicine is becoming more and more available thanks to technology. So it's just uniting those and then getting the funding in, right, to create those Nobel Prize-worthy major breakthroughs as well. So thank you so much for sharing all these different aspects today. Where can people follow what you're up to? Is there any other ways people should get in touch with you, or where would you like people to follow you on?

I'm on Twitter. I'm @JennGarrison, J-E-N-N-G-A-R-R-I-S-O-N. I'm on LinkedIn. And we have that website, juciralee.org. Like I said, it's a work in progress. We love feedback too. We're trying to build a knowledge hub that has information for women and physicians that's filtered through the lens of science and medicine. And where, you know, we're nonprofit, we're not trying to sell anybody anything. It's kind of a double-edged sword that there's so much interest in this space now that, you know, when women go to the internet to find information about PCOS or whatever it is they're dealing with, oftentimes what comes up are like factoids that when they click on them will take them to a website that's trying to sell them something. So we're trying to curate a space for information and cutting-edge research and all that stuff. That's literally just there to give you the information and not anything else. But we also have videos and links to pieces in the media. There's been a lot of media pieces recently. Yeah, just information. We have a white paper, we have a mission statement, all the buttons and information about how to reach me through email are there. And I'm happy to talk to anyone, like really literally, I give talks in person all the time. Particularly to non-science audiences. I give talks all over the world, and I'm also happy to talk to people on Zoom. Part of what we're hoping to do by building out this ecosystem is to galvanize and to really motivate ambassadors, like non-scientists, thought leaders, people like you, people who are passionate about this and who can spread the word about what we're doing, but also just spread the word about this space in general. You know, I think there's a slide sometimes that I show, and I've seen other people show that says like, why didn't anyone tell me? And it's gut-wrenching piece of what everything we're talking about is that many women don't understand these basic things about their bodies until something goes wrong, until they go to use their ovaries and they're not working, or until they come up against perimenopause and no one's ever told them, a doctor, nobody has ever told them that these things are going to happen. And it's a terrible shock to most people. So just educating women about their own physiology is a big piece of this. So we want ambassadors, we want anyone who has an interest to be part of our network and our community.

Beautiful. And I wanna ask you one question. I was reading and then had it in my newsletter today about the study on rapamycin for extending ovarian aging.

What is your view on that? Oh yeah. From Yuxuan Xu and Sev Williams at Columbia. Yeah. So Yuxuan was one of our inaugural grantees. Yuxuan got a grant from us which funded some of the really innovative and the first ever single-cell sequencing, single-nucleus sequencing on human ovarian tissue from young, middle-aged, and older women that really, I mean, these are the first datasets. I mean, that's horrifying to say, but the first datasets like that. And then she took that initial work and she applied for a bigger grant to do this intervention study in humans. So a clinical trial to ask whether or not rapamycin has an impact on ovarian aging. I think it's great. I don't think just in general, this is a much larger conversation. I don't think that rapamycin will be an intervention. There's a lot of reasons why you definitely don't wanna take rapamycin, even low doses of rapamycin. I mean, who knows actually, you know what, I'm step back and say we don't know. But I think, you know, if that trial is really important because if it's successful, then that tells us that mTOR inhibitors are a viable path to potentially modulating reproductive aging, ovarian aging, that would be huge. And there's lots and lots and lots and lots of different kinds of rapamycin-like molecules that aren't actually rapamycin that have, you know, the features that you want to keep and get rid of the negative side effects that you want to get rid of. So that would open up a whole therapeutic avenue, right? So it's amazing. And I'm very proud to say that we nucleated the work that led to that, right? We also funded a project in our first round to Mary Zielinski at the Oregon Primate Research Center. And that was the first preclinical study of rapamycin and mTOR inhibitors in rhesus macaques, which is maybe the best non-human model of ovarian aging. And, you know, those are foundational studies. You have to do these preclinical research studies to feel confident to go into humans.

Jennifer, do you have any final ask recommendation or any parting thoughts or message for my audience today?

Specifically for your audience, I would say I'm not a medical doctor, so I don't give medical advice, but I do think it's important to remind people always, especially women, that the interventions that we think about that have the biggest impact on healthspan that we know about right now as aging researchers are diet and exercise. And people don't want to hear that, but they are incredibly powerful. And if you were to do a clinical study that compared head-to-head diet and exercise interventions with rapamycin or metformin or NAD boosters or keto diets, whatever, all of these things that we hear about in the news with respect to healthspan and longevity research, if you did a head-to-head clinical trial, I promise you that diet and exercise would win by orders of magnitude. Everyone has it in their ability right now to think about how to optimize those things. And for ovarian health and reproductive aging, it's exactly the same story. We know that the things that impact aging in the rest of the body also impact ovarian health. And so I would just encourage people to think about that.

Thank you so much, Jennifer, for coming on today. Yeah. As always, a pleasure to speak with you and look forward to staying in touch with you. Yeah.

Thank you.

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