Epigenetic Clocks in Patients with Cancer with Dr. Christin Burd

Cancer acts as an accelerator of aging. Furthermore, we know that cancer and cancer therapies can elicit aging-associated cognitive phenotypes and reveal or exacerbate underlying cognitive deficits, increase the risk of physical impairment, heart disease, diabetes and other chronic health conditions, and accelerate the hallmarks of aging. 

Dr. Christin Burd and her team, from The Ohio State University, have been asking key questions about just that… age-acceleration in cancer. To understand this further, they have been researching cancer therapies, T cells, senescence, and p16 and how they are related to epigenetic aging. 

T cells, senescence, and p16 are all known to play important roles in cancer development and progression. T cells are key players in the immune system's response to cancer, while senescence is a process that limits the proliferation of damaged cells and is implicated in aging and cancer. P16 is a tumor suppressor gene that is often mutated in cancer cells. By studying the relationship between epigenetic clocks and these key factors, we hope to gain a better understanding of how cancer cells develop and progress, as well as how they may be treated. Aging biomarkers, including epigenetic clocks, may provide important answers to some of the most pressing questions in cancer research today.

In this week’s Everything Epigenetics podcast, Dr. Christin Burd speaks with me about the importance of biomarkers and epigenetic clocks for older adults with cancer, as epigenetic clocks are currently not trained on cancer populations. We also discuss the development of a new ‘p16INK4a epi-clock’ (that I am most excited about) which may allow for the measurement of different aspects of aging using the same platform. 

Being an educator at The Ohio State University, Dr. Burd is passionate about diversity, equity, and inclusion (DEI) initiatives in science. Dr. Burd continues to focus her research on identifying mechanisms to prevent melanoma and improve clinical outcomes in older adults with cancer.

In this episode of Everything Epigenetics, you’ll learn about: 
- How Dr. Burd became interested in cancer and what led her to the career she has today
- Aging as a risk factor for cancer 
- What cancer therapies are causing aging and how that process can be mitigated 
- The collaboration between TruDiagnostic and Dr. Burd’s team
- Ohio State’s CARE Clinic
- The main mission of Dr. Burd’s ;lab 
- Why we need biomarkers for older adults with cancer
- Using T cells to measure Epigenetic Age
- How T cell Epigenetic Age relates to clinical measures of faulty, cognitive decline, and toxicity risk
- Details of the cohort Dr. Burd is investigating
- How cancer therapies are related to Epigenetic Age
- How cancer patients Epigenetic Age relates to outcomes 
- Senescence markers and how they are involved in Dr. Burd’s work
- The pros and cons of senescent cells
- How to measure senescent cells
- If T cell p16INK4a levels and Epigenetic Age are equivalent measures 
- How p16 levels are currently measured
- How to get involved in the field of science 
- Dr. Burd’s advice on navigating the transition from highschool to college
- The grant application process and why there is a lack of understanding here

Where to find Dr. Christin Burd:
Dr. Burd’s profile at The Ohio State University - https://u.osu.edu/burd-25/
Twitter  - https://twitter.com/christinburd

Transcript

[hannah_went]: 0:00

Welcome to the Everything Epi Genetics podcast, Dr. Bird, I'm excited to have you here today.

[christin_burd__she_her_hers_]: 0:07

Now this is great. I'm so happy be here with you and to talk a little bit about our research together.

[hannah_went]: 0:13

Yeah, absolutely so. I don't know if I've ever told you this before, but I'm actually from north of date in Ohio, So grew up as a buck, Really small small town called pick Wad, But you know, loved watching Ohio State Um, growing up all of their sport. So when I remember first, like talking with you or sending emails back and forth with Know True diagnostic, I was like this is a dream come true. I can't believe we'll be working with you know someone with your experts from from S. U. So Before we hop into more of the research in our larger discussion today, can you just give our listeners some background information about yourself and you know, especially your expertise and cancer. What led you to become interested in this and in the career you have today?

[christin_burd__she_her_hers_]: 0:57

Yeah, sure. so as you mentioned, I grew up in Ohio. I grew up in Cleveland Heights and went to Cleveland Hights high school, which is now famous for the two Kelsey brothers. That was the same high school I went to for the Chelsea Super Goal. Face off. They're a little bit younger than I am, but not too much we'll say, And that's where I really got interested in science, and I think a lot of students get interested in science and high school, but they don't know what to do with it next and I was one of those people. I went to college thinking I want to use science to better the world and really had no idea how to do that. I think I tried out. You know a lot of different majors, trying to figure out where my fit was in those different majors thinking. Oh, you know, you have to be a physician or physical therapist or something like that to make an impact on people's lives, But when I got into laboratory, I just fell in love. It was an eye opening, an amazin Situation where people were interacting and talking about the science and trying to figure out figure out really complex problems and how to solve those and no complex. No problem is more complex. I think that cancer, I mean, this is a cell of our own body that has basically changed itself to become kind of evil nemesis. And how do we distinguish? How do we teach our bodies to find those evil Among our healthy normal selves Very challenging. how to come out in this. And so that was the big thing that drew me to cancer research was just the complexity of the problem, the number of people that are affected and just the wonderful cancer research community that's out there.

[hannah_went]: 2:47

Yeah, that's that's great. That's such a good way to explain it as as well you know, the cells of our own body. Really, you know, betraying us, so to speak, I think is

[christin_burd__she_her_hers_]: 2:57

Yeah,

[hannah_went]: 2:57

a good way to put it, but you couldn't be more right regarding the science major comment, right, I was the same way I went. You know animal science than biology. I was like. that's probably too general. Do I do bio chemistry? chemistry? I mean, physics. Who know so well, We'll talk about that at the end there, and maybe you know what will help navigate some people going through Same thing, Because that can can be difficult, but moving more to our our conversation, an Epi, genetics and cancer. You know, In twenty twenty you, you actually published a paper on nepigenetics as it relates to age and cancer, so I'd love to hear a little more just you know what you're doing now, and the main mission of your lab, as it currently stands, you know to give our listeners a little bit more insight, True diagnostic and dor bird, You know all of the work that you've bee. And we've been. We've been doing some things for quite some time, and we'll talk about those projects here soon, too.

[christin_burd__she_her_hers_]: 3:53

Yeah, so I have for a long time been interested in the connection between cancer and aging and aging is a respect for cancer. When you get older, you're more likely to develop cancer. but cancer therapy is also accelerate aging, so it's kind of this circular issue where you get older and you're more at risk for cancer than you get treated for cancer. And that makes you even older, And that causes other problems for Health span. And so we've been really interested in understanding both that initial part. You know what about aging makes you more at risk for cancer. But then also what therapies are causing aging. How those that process might be mitigated, And you know it's really wonderful to see so many cancertherapies coming out and patients have options, And I think now we really need to think about. You know, During the course of that selection of options, what is the long term effect of each one of those therapies

[hannah_went]: 5:00

Hm.

[christin_burd__she_her_hers_]: 5:00

for people? Not just you know, here's four different potentially curative options, but which option is going to give you the best healthy outcome Long term, And so that's kind of where we started to partner together with two diagnostic, because you have such a wonderful cutting edge biologic clocks that we can use the epitone Profiles, and you know great vio and thematic support meaning that we can take some of the knowledge about the changes in the epogynom and then dig through it to try to understand what the underlying process are that are causing that change. And I think that's what's really amazing with partnering with you is that we can get at the biology. What is causing these changes, not just measuring them, So that's been a fantastic collaboration.

[hannah_went]: 5:53

Yeah, I know you've been in touch with Vrundwarkhe's. our head of Violent Fromatichat, True diagnostic, and then Ryan Smith, as well. So so some colleagues and we'll continue to learn insights as these interpretations grow and we're able to uncover more. So super excited to be working with with you on that. I want to talk a little bit more broad picture, and then we'll go really into the specifics, because there's so much exciting work that that you're doing, but we, we essentially are Using the Epi genetic metholatian markers and interpreting them for age outcomes In some other insights as well. But you know why do we even need these bio markers in in the first place for for adults with cancer. I know you. Maybe you can connect that then to the therapy outcome or different? Uh, yeah, cancer therapyes,

[christin_burd__she_her_hers_]: 6:44

Yeah, so I'll give you the perspective from our clinical team.

[hannah_went]: 6:47

Okay,

[christin_burd__she_her_hers_]: 6:48

So here at Ohio State, we have a clinical team that works in a specialized clinic called the Cancer and Aging Resiliency clinics, or care. And what the care clinic is is some multi disciplinary clinic, Meaning that there are lots of different types of practitioners that visit the clinic, And so a patient will come in and we will holisticlly look at their health, so we'll look at the kind of medicate And they're taking to make sure there aren't interactionts. will look at their cognition, will look at their physical function and fitness will look at their social support networks and try to build those and increase those. But at the same time we're going to look at these umbiomorkers and of aging, and one of the reasons we want to do that is that we recognize that patients are often excluded from clinical trials Or excluded from particular therapyes based on their chronologic age. So just you know what your ages on your birth based on your birth certificate. But we all also know people who are eighty and running marathons right. So these people are probably more fit than I am. And so we really need to think about how we're making those cut offs so that we can insure that we're giving the best therapy to everyone. Also That in the individuals who may be more at risk or more frail, that we're not causing long term disability by a particular treatment option. So this is really where these bio markers are critical and decision making. We can't just assume that a clinician can look at a patient and decide O. this patient is gonna do really well in this therapy. And you know they'll come out great. There was a study done in older adults over Sixty, and they asked older adults we if we had a cancer. All these older adults had cancer and they asked them if we had a cancer cure for you that would cause disability. Would you take it? and seventy per cent of them said No, They did not want to live with a long term disability And so thinking about that right. Is it worth it to cure your cancer? If you can't live Your own, Um, and I think for older adults, quality of life really matters, And that's why these aging buyer markers are really going to help us improve the quality of life for our patients.

[hannah_went]: 9:24

Yeah, that's that's interesting. So you're using these Epi genetic markers as a way almost for inclusion and exclusion criteria for for different studies with the people who have cancer. Of course, Is that correct? a way to claim that,

[christin_burd__she_her_hers_]: 9:37

So that's how we want to do it. I mean, right now we're working to pair that and look at outcomes to figure out. Will it be more informative for physicians? For the most part, What we're finding is that a lot of people are being excluded that shouldn't be,

[hannah_went]: 9:53

Hm,

[christin_burd__she_her_hers_]: 9:53

and so I think it will lead to more inclusiveness, which is great, but also we do want to prevent. you know, those small number of people who we wouldn't predict would have a really terrible reaction

[hannah_went]: 10:06

Hm,

[christin_burd__she_her_hers_]: 10:06

to their therapy If we could tell them. You know, Yeah, we can still give this to you, but you know, maybe it would be better to use this other therapeutic option that's known to have fewer design effects. Um, so those types of decision have to be made on the fly every day in the clinic, and they're often just clinician specific. you know. they're just. they. call it the eyeball test

[hannah_went]: 10:29

Oh,

[christin_burd__she_her_hers_]: 10:30

right there, Just looking at the. They're just looking at the person and thinking. Oh, you know how frail or fit is this person we need buy Markers. We need quantitative measures. We don't want people just giving us a once over

[hannah_went]: 10:42

Yeah,

[christin_burd__she_her_hers_]: 10:42

and making dispense.

[hannah_went]: 10:44

we need to remove the guesswork right that

[christin_burd__she_her_hers_]: 10:46

Yes,

[hannah_went]: 10:46

I've all that makes me cringe. almost. Um,

[christin_burd__she_her_hers_]: 10:50

it makes them cringe too.

[hannah_went]: 10:52

they know it. so I think it's just

[christin_burd__she_her_hers_]: 10:53

eh,

[hannah_went]: 10:55

and you know, incorporating something better right, kind of just to make those studies even better have better insights right to make changes in different assumption. So know that's that's great to hear that that you all are working on that. for for that reason, um, Changing subjects are going a little bit deeper. I could say a lot of the work you're you're now doing is with with T cells right. So that's a big part of what you know to diagnostic your team have been collaborating on. So what about T cells? Can? Can we use these types of cells to actually measure Epi genetic age? And you know we may have some some listeners who aren't super familiar with T cells as well, So if you want to give an introduction to C, T cells, that would be great.

[christin_burd__she_her_hers_]: 11:41

Yeah. So in our blood, so most of the epigetic clocks that have been developed, the measures that we use have been based on blood or tissue samples, and in your blood there are all kinds of different cells that are circulating. Some of them are our immune cells, and even among those immune cells, there's all different types of immune cells. There's immune cells that attack cancer cells. there's immune cells that suppress auto immune diseases. there's all different kinds of immune cells that circulate, And when you get an infection, you probably realize this, as those cells will expand and build their armies right, and then you will have swollen limp nodes, or maybe even a fever from them getting activated, and one of the key immune cells that's involved in both responding to infections as well as responding to cancer and killing cancer. cells, already cells called T cells. And so we're really interested in T cells, as as they pertain to cancer and cancertherapies, especially in munotherapies. A Lot of the munotherapies that we're using. Now, these new generation molecules they target and try to activate T cells to kill your cancer cells. And so we thought well, if you're measuring epogenetics in all the blood cells, and we know That your blood changes as far as what different types of immune cells are in there on any given day, right, we may just be measuring changes in the populations of cells that are there.

[hannah_went]: 13:22

Hm,

[christin_burd__she_her_hers_]: 13:23

What if we can focus in on a specific cell type and understand how the apogentics of that cell type are changing over time, or the aging of that cell type is changing over time, And we pick T cells because of their importance in cancer and immunity. And so that's where we began to do this research. But can you measure epigenetic agency cells getting back to your question? While we had to really partner with True diagnostic to figure out the answers, this question, and what we did was, we were able to take blood samples and then purify T cells from the same person and send them to true die Diagnostic. And they did the analysis, and then we compare their results, and indeed you can measure aging and T cells. It gives you a little bit of a different number than if you just measure the blood. So it's telling us that there is something different between the cells and the blood, But we are working together and partnering with true diagnostic to really understand what this means for patients and why these differences occur so that we can better Taylor therapies and outcomes?

[hannah_went]: 14:34

Yeah, that's just. it's so cutting edge. It makes me smile from from ear to ear.

[christin_burd__she_her_hers_]: 14:37

Yeah,

[hannah_went]: 14:38

I think the looking at the specific nowepigenetic metholationmarkers and outcomes and the different cell types is the future of genetics right. It's already been discovered that there are differences, so now we need to understand what those differences actually mean right. so I think again, I just love the work you're doing. How we can start to relate this to different clinical decisions are Or outcomes. Um, So I know you know you've even looked at these these cell Epi genetic ages and its relationship to maybe things like clinical measures of you now, fertility, cognitive decline and toxicity risk. So are there any correlations there?

[christin_burd__she_her_hers_]: 15:20

Yeah, so still building out those data sets and we are starting to see some signals where you know. in small cohorts, there are definitely associations between the genetic clocks that we're measuring and things like frailty or risk of hospital readmission. Things like that Nero cognition. So as we build these out, we're going to have to expand them to additional Centers around the United States so that we can capture larger populations, and we're starting to do that now, which is fantastic. You know, we're expanding. We're starting some clinical trials to really understand if we can validate these such that they can be used on a regular basis in clinics all over.

[hannah_went]: 16:10

Yeah, and what cohort are you using for that or or what? What patients? Can You talk a little bit more about the patients that you're You're looking at.

[christin_burd__she_her_hers_]: 16:17

So our biggest focus right now has been on my Loma patients, Because of we know that there is a lot of accelerated aging that goes on with the treatment for mialoma, which is often an autologus Bo marrow transplant. So they're taking their own mune, them celles, and removing them from the body, are radiating the person, so that that person's cancer cells are killed and giving them back their stem cells to read, Populate and remake their immune system, And that process is really dramatic and causes a lot of accelerated aging. And so we've been really focused on that particular group because we know it's It's such a problem there and then the next group that we've been looking at are individuals with what we call solid tumor, So those that don't float around in your blood, and those would be things like lung cancer And melanoma, where we are using a munotherapis. because obviously we're really interested in T cells, and T cells are what's being targeted by a lot of these uotherapies. So those are two major cohorts right now that we're looking at, and all of our patients enrolled in these studies right now, or six year old, or because we are trying to capture some of the the functional deficits that occur with a

[hannah_went]: 17:45

Sure, Sure, and I forget the name of the first cancer therapy you mentioned. But these all of these therapys you're using that was my next question. Do they show a link to Epi genetic age, or I don't know. if you can know. Maybe go

[christin_burd__she_her_hers_]: 17:57

Yes.

[hannah_went]: 17:57

over each of those those therapies.

[christin_burd__she_her_hers_]: 18:00

Yeah, So really interesting for each cancer type and for each person can the therapyes have become more and more individualized right. So there are a lot of different decision making points along the how we decide who gets one. One of those is the genetics of the tumor, So what types of genetic mutations are present? Another is a person's cronologic age, which Like to eliminate, and then the type of cancer. Obviously, so we have people receiving all types of therapyes. What we have found is that for individuals receiving chemotherapy, if you take the measure, their epogenetic age before they start chemotherapy, and then even long after, like years after they received their last dose of chemotherapy, Epogenetic aging is very prevalent. You can see that in their blood, and we also see that with munotherapy, which is pretty new observation. I don't think a lot of people have looked at this yet, but that may mean that people who have been cured of their cancer with immunotherapy, may be at risk for other types of age related diseases. The one thing that's super interesting though is that we've seen some patients are treated with Uhdmethalation inhibit, So their cancer type is actually treated with a drug that inhibits den metholation. And we see that those individuals appear to be doing better after therapy, so we're wondering, You know, is it improving their epogenetic age? And if so, how and could that be applied to healthy people, too? If this drug were implemented for a short term and Healthy individual, would they potentially reverse aging? And we'll probably talk about that more later, our goals and reversing aging. But yeah, that's one really cool finding we've had is that there are some very specific targeted drugs that seem to have kind of an anti aging effect.

[hannah_went]: 20:17

Gotta interesting. So you said that drug. Let's yeah, hold on to that point for

[christin_burd__she_her_hers_]: 20:21

Oh

[hannah_went]: 20:21

a second. You said that drug is going to remove metholation.

[christin_burd__she_her_hers_]: 20:26

Yes,

[hannah_went]: 20:26

Okay, so give you the expression

[christin_burd__she_her_hers_]: 20:28

yeah,

[hannah_went]: 20:28

of those gens in keeping those gens turned turned on. Essentially, Yeah, that'd be

[christin_burd__she_her_hers_]: 20:32

Hm,

[hannah_went]: 20:33

interesting. Have you done anything in a healthy cohort? Then with people without cancer in that drug?

[christin_burd__she_her_hers_]: 20:37

We. we have. not. So this is really the first piece of first observation of this in a cohort. Not many longitudinal studies have been done meeting that you take the same person and you follow them over time as they start therapy and continue therapy. So we have one of the now. Our clinic is really nice, and that we can have patients come back time and time again and really follow what's happening with them. And that's what's led to this kind of unique Iscovery. And you know, as we try to understand the mechanism by which that is happening, and collaboration with true diagnostic, we really hope to bring that forward to apply it to more people.

[hannah_went]: 21:21

That's exciting. I think a lot of times when you're you're treating these. Um, I don't know the right word to use. You know, maybe more diseased based populations are cohorts and you're trying different therapy. Seeing what works you see. some really great effects like they're doing now with the lytheum and in people with by polar disorder, They actually, you know, think maybe lodoslytheum could have some some reversal with these epigenetic age clocks. Even the lytheum has been studied for a very, very long time in aging, So it's great that you have This cohort. Especially with the care you all. do. You're able to get them back in the clinic and do some longitudinal testing like you mentioned.

[christin_burd__she_her_hers_]: 22:00

Yeah, and then pare that right with how are they feeling? Whether

[hannah_went]: 22:04

Hm.

[christin_burd__she_her_hers_]: 22:04

what is their function like? So I think it's really important that we show that these epogenetic markers are improving the physical function and lives of these people as well. So that's what he is nice about longitudinal studies.

[hannah_went]: 22:19

Yeah, of course, yeah, and I can't believe I know I didn't comment on it, but yeah, you said. the seventy per cent of people who took that survey said they would you know, not want a therapy if they were to be disabled later on, right to get rid of that cancer. So I think that's huge, too. right. They, they want something that works and you know they want to be cured. They don't want to have any any side effect, So really paying attention to what the patient wants right is definitely key.

[christin_burd__she_her_hers_]: 22:47

Yes,

[hannah_went]: 22:48

So how do you? How did the patient Epi genetic age relate to different outcomes? I know you may have hinted on this a little bit, but can you expand that?

[christin_burd__she_her_hers_]: 22:58

Yeah, so we have not seen any dramatic change that's associated

[hannah_went]: 23:03

Hm?

[christin_burd__she_her_hers_]: 23:03

with the outcomes yet. of course all of our studies are somewhat limited. And how long we've been following people? You know, a lot of cancer studies really require five years, sometimes even ten years to figure out how many of those people had disease recurrence. How many of those people remain healthy. Did they succumb to other diseases? Also, Ovid has not helped things, and interpreting data that's made it much more complex. so I think that you know will know in the in the future, but right now really early on we haven't seen a specific signal M. but you know again, it really takes a long time for those data to mature.

[hannah_went]: 23:51

Sure, sure we'll learn. and yeah, of course, Covid, nineteen, adding another variable or layer to to look at there, so it doesn't make it easy on you all. Are you know the people who are actually doing a lot of that that data mining? Um, we're gonna switch though to senescence, so I think probably almost everyone listening is familiar with Senescence, right? It's as buzz word. It's really popular and agin right now, and it's one that is notoriously difficult. as you know, what defines a senescent, So this is differentiated by by cell types. So were I think, still learning a lot about this. Even the definition of this word, Um. Can you explain senescence and then can you talk about how these senescent markers are involved in your work?

[christin_burd__she_her_hers_]: 24:37

Yeah, so senescence was discovered a really long time ago when research was started growing human cells in the laboratory. And what they discovered is that Atter, you know, so many months of growing them in the lab, they would just suddenly stop growing and they were trying to figure out why this was happening, Nd. what they found out was that at the end of our cromozones there as some repetitive A sequences, they're kind of like insulators that sit at the end of each cromazone, and every time a cell replicate, they get a little shorter, and if they get too short, then the cells actually start to lose their genetic material because the insulators on the end fall off. And so these shortening processes would lead to these cells not growing any more, and they would just sit there in the dish. They would sit there for months on end doing nothing. Um, and so we you know, started to notice that this occurs with lots of different cell types, and then people began to find them in the body that you know, as we aged, you could see that some of these cells were appearing in almost every tissue, and that led to this idea that these were probably negative. In some way. These these

[hannah_went]: 26:05

Hm.

[christin_burd__she_her_hers_]: 26:05

cells, So senescent cells, kind of can occur and response to various stress, or so for instants. If you have a G mutation that could lead to cancer in a cell, sometimes that cell will just become senescent, which is great, because you don't want to cancer. It basically will sit there and won't divide. It will just kind of chill. I like to draw. senscencells is like sleeping on a pillow.

[hannah_went]: 26:33

There

[christin_burd__she_her_hers_]: 26:34

like

[hannah_went]: 26:34

you go.

[christin_burd__she_her_hers_]: 26:34

your there, dormant there there kind of Hang it out. chilling. Um, And, but the problem is that they don't help either. they're kind of lazy. right? So if you have tissue damage or injury, then what happens is they don't help to repair that.

[hannah_went]: 26:54

Hm.

[christin_burd__she_her_hers_]: 26:54

And so that's a problem. We have all these kind of bystanders just standing by looking at the damage and not doing anything. We've also learned that scenes and cells can make Um, various signals that increase inflammation

[hannah_went]: 27:10

M.

[christin_burd__she_her_hers_]: 27:10

and inflammation is not a great thing. When we don't need inflflammation in our body. we don't want that going on. so what we've done is try to understand the molecular changes that occur with Senecas, but those are very different in a lot of different so types, So that's where there's so much confusion about what is a senescitself, Because I think if you look at any given sell type, how it adapts and how it decides that it's going to become this sleepy by standard is a little bit different. There are lots of different metrics out there that we are trying to apply things like the expression of a tumor suppress or gene called P. Sixteen. Sometimes used shortening of those insulators on the end of the day called tamers Can be used Um, but these often need to be paired with other aging by markers like an empagenetic clock or things that will measure some of these inflammatory side kinds,

[hannah_went]: 28:19

Yeah, just so we

[christin_burd__she_her_hers_]: 28:19

so

[hannah_went]: 28:19

can

[christin_burd__she_her_hers_]: 28:19

that's

[hannah_went]: 28:19

learn more about

[christin_burd__she_her_hers_]: 28:20

yeah.

[hannah_went]: 28:20

them, You mean

[christin_burd__she_her_hers_]: 28:22

yeah, it's just because they're so complex. not every Cenesand cell is exactly the same thing, right, so we can't pick one particular by marker and measure them all. If that makes sense.

[hannah_went]: 28:35

Yeah, definitely, and the senescent cells I always hear. I'm referred to as these zombi cells. right. I think it's so. Um, You know such a buzz word I mentioned just because people are realizing, like, Oh, we have these cells that you said are dormant or are sleeping. You know what do we do with them? Type of thing? you know, people who are really involved in their own health. Or maybe you know, quote, Unquote bio hackers. So are you said? The senescent cells? I really liked how you describe them as bystanders. Is, Are any senescent cells good? or do you want you know? None at all, Or do we not know? Do we need more research?

[christin_burd__she_her_hers_]: 29:09

Yes, so sonesencels actually play some important roles and things like room healing

[hannah_went]: 29:14

Yes,

[christin_burd__she_her_hers_]: 29:14

and things like you know, processes like that. So they are important and they're also important. If we didn't have senescence, you would be at high risk for cancer because our gnomes aren't perfect, and even in replicating cells we make mistakes, or just going outside environmental carsenegens. whatever we're exposed to in life can cause genetic mutations that would promote cancer Most of the time. What our body does is, it responds by triggering senescence. And so you know, that's why we do constantly get cancers right. So senescence is good in some ways, but I think this long term accumulation over a lifetime. Once you start getting up higher and higher, and the frequency of those by standards gets higher, then your ability to recover from things Starts to suffer, and that's the problem.

[hannah_went]: 30:11

Sure, maybe need to healthy balance. Whatever you know, healthy means right. We don't want too much for for the inflammation. you know indication of cancer as, but you know we. We don't need too few either. We need some standing by to to again help remove that that cancer so interesting and I know a lot of researchers out there are doing work on different synalytic therapys, and maybe how to clear out some of those senescent cells as as well. But I want to talk about. You mentioned that the P sixteen. So that's really exciting part of the research we're doing with you. Um, so maybe I know you mentioned there to much suppressor protein. They play a really great role, you know, sell psycho regulation. But do you just want to define P sixteen, and then sometimes it's also know P. sixteen ink for a correct

[christin_burd__she_her_hers_]: 31:03

Yes, so

[hannah_went]: 31:04

perfect,

[christin_burd__she_her_hers_]: 31:04

P, Sixteen ink for A Is it's full name? The reason that it's called Psixeen is based on the size of the protein. So there are other pertins that are the same size. So if you go into another field and you're not in a pale, then you c. P. sixteen, they may mistake it for something else, so that's why sometimes you see ink for a put on the end just to kind of key Is right.

[hannah_went]: 31:34

M.

[christin_burd__she_her_hers_]: 31:34

What we're talking about, what pecten does is it's turned on. It's a Gen that's turned on when cellstressers are detected, so we have almost none of it and most of ourselves. But if we have some sort of cellstresser that comes along and triggers that like a gene mutation that lead to cancer, Um, P, Ten gets turned on. and what it does is it halts. The cell keeps it from Dividing until it can either fix the problem or if it can't fix the problem after a while, it will essentially put it to sleep. so it becomes a bystander sold and becomes senescent, So what's been interesting about P sixteen is that when we realize that P sixteen increases with age, people said Oh, and it increases in senescent selves We thought. Oh, this could be a cireget of how many Senesencells you have in your body

[hannah_went]: 32:36

M.

[christin_burd__she_her_hers_]: 32:36

Now, lots of studies have been done linking your tea. how much psixteenyour T cells make to things like your fitness or frailty, your risk of hospital, re admission, and things like that, So we're beginning to understand P. sixteen as a cureget For how many scenessen cells are in your body.

[hannah_went]: 32:59

Gotha, And maybe backing up. Is there a current way we can actually measure the number of senescent cells in your body?

[christin_burd__she_her_hers_]: 33:08

Not perfectly.

[hannah_went]: 33:09

Yeah,

[christin_burd__she_her_hers_]: 33:09

I think we

[hannah_went]: 33:09

right,

[christin_burd__she_her_hers_]: 33:09

try to get back to right that that question that you asked about how do you measure son and salad and there's no perfect way to do that right now.

[hannah_went]: 33:18

Perfect,

[christin_burd__she_her_hers_]: 33:19

So yeah, and in the past we've really focused on T cells because they were

[hannah_went]: 33:24

Hm,

[christin_burd__she_her_hers_]: 33:24

easily accessible from a blood draw,

[hannah_went]: 33:27

Yeah,

[christin_burd__she_her_hers_]: 33:27

and that's where a lot of the peoftendata comes from.

[hannah_went]: 33:31

Yeah, and that was. I want to ask that question before I ask this one Because again, why your your work is so ground breaking. So are these you know? these P. P. Sixteen levels in these T cells are those equivalent with with Epi genetic age measurements? Or are those senescent call measurements? Is that a way? Maybe we could start to learn more about that?

[christin_burd__she_her_hers_]: 33:52

So very interestingly in partnership with your diagnostics, what we've been able to do is take T cells from the same individual and look at the pixteamlevels and then all the different epigeneticclocks that you're developing in another groups, and they appear to be different measures, so they don't necessarily match up. But why is that exciting to us? Well, that's exciting because we think that it's their Ring. Two different types of aging right. They're measuring two different occurrences. And if we could build an epigenetic clock that would predict P. sixteen levels, then we could kind of integrate those two types of aging into one metric. And that's what we're trying to do. It sounds very complex, but essentially as I described before, you know, aging and senescence can be, you know, measured in many differ Ways, and if we can capture as much of that complexity and put it into one metric, it will make it much simpler to kind of judge outcomes for patients.

[hannah_went]: 35:03

Yeah, and I think that initial data is very very exciting. Um, so I think we're you know, Hopefully getting a lot closer to you now creating one of those those predictors. Essentially, which would be huge. Right, We would be able to. Then you know you will be able to talk better about the application than than I could, but be able to look at you know. Maybe those different cancertherapys look at different, just interventional therapys, For you know more of your your healthy populations and see Be what's reducing senescent cells. Or you know what may be working in a way that we thought it wasn't before, So I think that is again something that super exciting.

[christin_burd__she_her_hers_]: 35:44

Yeah, I know it's great. I mean One of the things that's been really challenging about P. sixteen is it's hard to measure.

[hannah_went]: 35:51

Hm.

[christin_burd__she_her_hers_]: 35:51

Re using Ran to measure P. Sixteen. It's not a stable. Is d N out in, you know normal conditions in the laboratory, We can you know, stabilize both. But so if we want to reach people who are in areas where they're using a community hospital, how are we going to eat? P. Sixteen, Very challenging and I think by using d, n A and epigenicbased measures of P, sixteen or cirguts of P, sixteen, we will be able to reach people all over the world, and that's something that we would love to be able to do, and to really measure senescence in a more global population, not just in the people who live close to a laboratory,

[hannah_went]: 36:39

Yeah, yeah, I think that's a great point as well. We want to make sure that everyone can can use this type of testing, right, Epi. genetic methilation. In general that the testing is so new. it's definitely not the cheapest. I understand that you know first hand, but hopefully just like you. No mix. You know, now you can sequence your entire, Do you know for less than a hundred dollars, less than twenty four hours? and you know, hopefully Epi genetics will get there one day, But the insights you can learn from you know, looking at an entire, About a million of those metholation markers is phenomenal There's there's so many different insight. So yeah, very cutting edge, very exciting. and I'll wrap up more of the research talk, and then we'll talk more about you as an educator at at Ohio State. But what's next for you in the research realm? Are you trying to wrap up some of these studies or you? Now? what are you working on right now?

[christin_burd__she_her_hers_]: 37:32

So I say, in terms of these studies, we are

[hannah_went]: 37:35

M.

[christin_burd__she_her_hers_]: 37:35

trying to build that sines clock, and really tested right in multiple population, So that's

[hannah_went]: 37:42

Hm,

[christin_burd__she_her_hers_]: 37:42

one angle, the other is expanding some of these observations that we've seen with epogenetic clocks and outcomes and patients to include other universities and other sites, so that we can really understand the applicability broadly. And then I'd say the third area is how do we reverse this aging right? And one of the key is this, You can go back into this epigeneticdata as I alluded to before, and start to pick out the gens where this metholation work is modified, and we can go back in the lab and say Well, is the change and in the expression or the mtholation of that gen causing aging?

[hannah_went]: 38:31

Hm,

[christin_burd__she_her_hers_]: 38:31

If so, Then how would we turn that off or turn it back on? So these are the types of questions that you know will be long term in my laboratory. To really, you know, we want to have a long health span in everyone, not just cancer patients, but really to promote healthy aging for everyone.

[hannah_went]: 38:53

Definitely, I'm equally excited about all three of those points. I don't think many people realize the importance of the third point you mention, which is basically we're looking at the differentiated metholated region. So on on all of these metholation, you know patterns were seen. Which gens are they affecting? And if we can understand that, then maybe we know the mechanism of action that. Now, whatever therapy or kind of insights we're looking at is working by, So I just think that's so Van Bull. I think that's just so exciting as you know. This genetic field grows so well. We'll see, but I love all of the work you're doing, Dr. Birds. It's amazing. Um, shifting more to you. I'm excited to learn a little bit more about what you do, though from from an educational standpoint I know you know previously before we talked when we were doing this recording, you mentioned to me that the diversity in inclusion. you know all these initiatives. The d e I are our super impot, And to you and in science. Um, So you know, what are some pass forward for those who have an interest in this field? but they don't really know how to get involved. Maybe students or people of all ages, I guess.

[christin_burd__she_her_hers_]: 40:04

Yeah, For sure, So you know, I think this is an important topic to me because I see that there are students that enter Ohio State or people that I interact with in the community that have amazing interests and science, but don't have someone in their family or don't have you know a connection to a scientist, and so navigating and getting those Opportunities is incredibly important. So how do you if you like science like I did as a high school or, but you have no idea what you want to do like we both did. then, I think the best thing to look at are some of the programs that are offered through the National Science Foundation through local colleges and universities, including community colleges, and you don't have to live Near them. There are scholarships that are available to pay for your housing to pay for your food to get everything so that you can try out science, and you don't have to have experience in the lab to apply for these things. The thing that they're looking for on these applications is interest. Okay, so don't count yourself out if you're interested in science, and you don't have the skill Yet. That's all the reason to apply for these programs. And so I am going to give Hannah a whole bunch of listings to put with this podcast that you can go on line and look. These programs started the high school level. There are programs also at the collegian level. And then there are programs after college, So if you decide maybe research was something that I wanted to explore, but I just didn't have a chance or an opportunity tore in college. Um, let's do that. get that out there and then finally, for those of you who love science and are not necessarily college age, I'd like to encourage you to take advantage of a lot of programs are out there at universities Like at Ohio State, we have a program sixty, so program sixties For anyone over sixty can enroll for free credits And you just Come and audit the class. I've had several people come and audit. They've been some of my most exciting and interesting students.

[hannah_went]: 42:43

M.

[christin_burd__she_her_hers_]: 42:44

They have just such an amazing life story and they'll bring in their knowledge and background and really add a lot to the course. Um, so look at your community colleges and public and state colleges For those opportunities. some of them are even online so you can access them anywhere. Uh, yeah, and

[hannah_went]: 43:05

Yeah, that's great

[christin_burd__she_her_hers_]: 43:07

just go

[hannah_went]: 43:07

that,

[christin_burd__she_her_hers_]: 43:08

out there and find them.

[hannah_went]: 43:09

but that's great. and yeah, just get started right. I remember, I did some undergraduate research at the University of Kentucky, but it was so hard right because some, some, you know when you start to get into your your major and you're trying to navigate it, You know, I was a softmare. I was a junior. was like, Oh, maybe too late, because a lot of labs want you on, for you know, at least a year or two right, so just just start start looking at. You know those resources available. Put everything in the the show notes that Dr. Bird mentioned. Funny enough, I just went to a career far to try and hire some some students and get some in turns this summer at Uk earlier this week, And you know what's what I think even more disappointing is is you know they grew up through cofit, right that they might may not have some some laboratory experience right. So so that's something I thought about during when we were there and I was like, Oh man, you know, Um, they haven't gotten the opportunities that people have in the past So important to look at places like the N. s. f, or local colleges. I think that's that's great advice. You know. I even remember applying to colleges and being so nervous and scared. I applied to Ohio State and in Kentucky. Um decided to get out of Ohio, and you know, drive two and a half hours down down seventy five, but I was torn between the two. I really was. You know, I currently have have little cousins going through this process, and um, you know Again, my parents didn't have a scientific background at all, so so I had to navigate the field on my own, so maybe for any younger, you know, students out there, or even parents of students was just one piece of advice You would you would give to them. You know, if they're going through this process or even the application process for college right now,

[christin_burd__she_her_hers_]: 44:56

Yeah, you know, I think every college kind kind of looks for something different and it's it's hard to know what exactly to write, but I think in the end if you're true to yourself and you write where your passions lie, Um, that's going to help you with. you know, finding a match and maybe you think the matches Ohio State. But you know if you don't get in, maybe that really wasn't the best place you know for your growth.

[hannah_went]: 45:26

Yeah,

[christin_burd__she_her_hers_]: 45:26

Um, the other thing I would say is you know, make connections with people. Don't be afraid to reach out to individuals at universities that you're interested in. You know, I'll frequently get emails from people saying Hey Dr. Bird, Can you tell me a little bit more about the Department of molecular genetics where I work? What kinds of courses do people take? What kinds of things do people after they get into molecular Genetics do with their lives afterwards? What do your students do next?

[hannah_went]: 46:02

Yeah, that's

[christin_burd__she_her_hers_]: 46:03

So

[hannah_went]: 46:03

awesome.

[christin_burd__she_her_hers_]: 46:04

yeah, those are. Those are questions that you can reach out. We're just normal every day,

[hannah_went]: 46:08

Uh,

[christin_burd__she_her_hers_]: 46:08

people. I think that's

[hannah_went]: 46:09

uh,

[christin_burd__she_her_hers_]: 46:10

one thing people are like. Oh, they're the professors, but we're really every day people, and you can contact us and reach out all of our. You know, if you look on any of the web pages, there will be contact information to reach out and get more in Ation, So don't be afraid to do that and you know putting your name forward can be really important.

[hannah_went]: 46:33

That's That's great advice. I know I was so nervous. I was like, you know, I'm just a young student. They don't want to hear from me and that's just you know. Not true at all. I even love when people reach out to me. you know, from true, diagnostic or everything, genetics. Hey, what do you do? you know? What do you spend your time doing? And it's it's enlightening to talk to my cousins who are going through this process and ask me those questions. You know. Um, do you sit on the computer all day? You know what do you do? And I think that's That's great advice. Um, and really, one of one of my last questions here, Doctor Bird, I've briefly chatted with a lot of other people. My podcast about you know their research projects and how their funded. but I know you have a lot of experience and in this realm, so you know, you mentioned to me that this is an important important point, because I think the general public doesn't understand how hard it may be to get funding for for these types projects that you're at All doing. You know, I remember when I was in under grad and I would go to my professor's office for their office hours. They would have like a piece of paper that says you know office hours canceled working on Grant and I was like,

[christin_burd__she_her_hers_]: 47:44

Oh

[hannah_went]: 47:44

Come on, it couldn't be that hard. right. Well, you know, we have a full time grant writer here at True Diagnostic. We all review the grants. we you know, spend a lot of time making sure there are are no mistakes, So I definitely understand why they have to cancel their office hours. Um, so tell me about the process Like, And why do you believe there's like this lack of general understanding? You know, I know. I definitely don't understand it to the fullest either.

[christin_burd__she_her_hers_]: 48:13

Yeah, so I think some of its scientists don't talk about it right. We're on't

[hannah_went]: 48:18

You don't want to.

[christin_burd__she_her_hers_]: 48:19

but we gon go out to the general Republic and say, let me tell you about how I get funding.

[hannah_went]: 48:24

Hm,

[christin_burd__she_her_hers_]: 48:25

And so it's kind of a mystery. but in general funding is either run through foundation, so you may have heard of some like the American Cancer Society or maybe even the American Federation for Aging Research. These big foundations can support some awards, and but the majority of large awards come from the government, So

[hannah_went]: 48:51

Hm,

[christin_burd__she_her_hers_]: 48:51

through the National Institutes of Health, the Department of Defense, or other portions of governmental funding, and so, in order to get any of these grants, we will write proposals. They're varying in length. They also contain all of the ethical guy Lines and financial constraints that we're going to put on that project, so every single thing that we're going to buy over that period has to be line items listed, and that includes the salaries of everyone working on the project, So the university doesn't fund anyone working in my lab. I have to pay those people, so it's kind of like a small business, and I think people don't realize that that my small business of research is completely Funded by my,

[hannah_went]: 49:45

Yeah,

[christin_burd__she_her_hers_]: 49:45

by my own grants. The university does not provide the funds to support any one that works in my lab,

[hannah_went]: 49:52

Yeah,

[christin_burd__she_her_hers_]: 49:52

and moreover, some of my own salary has to be paid by those grants. so the university is, and paying my whole salary, they're paying part in it.

[hannah_went]: 50:01

Hm.

[christin_burd__she_her_hers_]: 50:01

So it's a really big deal because you're kind of managing and you're dependent upon these grants to pay your students, your your post, Undergraduates, or research technicians to keep the project going.

[hannah_went]: 50:18

Definitely, when I was doing my undergraduate research, I remember, you know, I would hear it from from my principal investigator. Hey, we'll see if we get funding the semester right. I mean, you could always stay on. Unfortunately it would be unpaid. But if you want to continue your research, you know, I was trying to get published with my paper and everything, so I basically had to continue. You know, if I wanted to get that paper out, regardless if I was paid or not, I was very lucky. you know he was able get funding for it for everyone in the lab. But it's It's not easy. like Mentioned, So I think you know. the more we talk about it, the more we understand the process. Hopefully you know we'll maybe see some changes or or the easier it will get as well.

[christin_burd__she_her_hers_]: 50:57

Yeah, for sure, I mean, once we write these proposals there reviewed by scientific commtcommittees, So you know, our own peers are reviewing

[hannah_went]: 51:06

Okay,

[christin_burd__she_her_hers_]: 51:06

the service a peer reviewer. Other people around the country serve as per reviewers, and there discussed and thoroughly vetted. But if you imagine we have, you know a ton of Ph. D. S. All these applicants are coming from

[hannah_went]: 51:23

M.

[christin_burd__she_her_hers_]: 51:23

Phds and M. Des. right. These are all very like in Tel Gen people,

[hannah_went]: 51:28

Yeah,

[christin_burd__she_her_hers_]: 51:28

but only ten per cent of those grants are being funded, so that means that if I submit ten grants right, but if it were just by chance, one of them might get funded, So

[hannah_went]: 51:42

Yeah,

[christin_burd__she_her_hers_]: 51:43

um, you know, it's a lot of time spent re submitting, and I'm sure you're you're,

[hannah_went]: 51:50

Yeah,

[christin_burd__she_her_hers_]: 51:50

you?

[hannah_went]: 51:50

and then and you

[christin_burd__she_her_hers_]: 51:53

So

[hannah_went]: 51:53

have to wait. Like after you submit, you wait. What is it? like? nine months, twelve months,

[christin_burd__she_her_hers_]: 51:57

It?

[hannah_went]: 51:57

maybe sometimes more.

[christin_burd__she_her_hers_]: 51:58

it can be up to a year. Yeah,

[hannah_went]: 52:00

Yeah,

[christin_burd__she_her_hers_]: 52:00

before you actually even hear back if you'll

[hannah_went]: 52:03

That was the most surprising part that I heard I was like. Well, you know, you mean we don't know tomorrow. we just submitted today. We don't know tomorrow right so they are thoroughly betted There's there's a process in place, but it definitely takes a long time, and it takes a long time to create the grants and submit them And you know more of the kind of administration work right, There's word limits and character counts and all that,

[christin_burd__she_her_hers_]: 52:26

Yes, and we have to be very. even when we get them. We have to be very careful about how we're spending the money right. I think it's It's a great investment because most of the money is actually supporting researchers and jobs right here

[hannah_went]: 52:38

M. yeah,

[christin_burd__she_her_hers_]: 52:39

in our community, so I think that's fantastic.

[hannah_went]: 52:42

Yeah, well, it's been great, Dor bird. I have one curve ball question always at the end of my podcast. If you could be any animal in the world, what would you be And why?

[christin_burd__she_her_hers_]: 52:52

Oh my gosh, what animal would I be and why there are so many great animals? So I am a huge fan of these cranes that come by in the water Here in Ohio, they've started to appear with these really long like, kind of this one Like necks.

[hannah_went]: 53:13

Yeah? Yeah,

[christin_burd__she_her_hers_]: 53:13

There's so beautiful and so I would love to be this majestic crane, Right because

[hannah_went]: 53:20

There you go.

[christin_burd__she_her_hers_]: 53:21

I feel like you don't know To do anything. You're just

[hannah_went]: 53:23

Yeah,

[christin_burd__she_her_hers_]: 53:23

majestic, right

[hannah_went]: 53:24

I've never heard no one in that yet, so I like

[christin_burd__she_her_hers_]: 53:27

right?

[hannah_went]: 53:27

it. It's unique. Well, thank you so much, Dr. Bird. you know we've We've come to the end of this amazing podcast interview for for people who know undergraduates, or maybe people who want to ask you questions. Where can they find you?

[christin_burd__she_her_hers_]: 53:42

Yeah, So you can find me at my email dress. Its bird B u r d Dot, twenty five at o s. Dot. and then I'll also provide some information for you to put in the links so that people can contact me if they have questions.

[hannah_went]: 53:58

Awesome? Well, sounds great. Thank you everyone for joining the Everything epigentics podcast. Remember you have control over your genetic, so tune in next time to learn more. Thanks again, Dr. Bird.

[christin_burd__she_her_hers_]: 54:09

Thanks.