hannah_went:
Welcome to the Everything Epi Genetics podcast, Kristen, I’m so excited to have you. Thank you for being on today.
kristen_mcgreevy:
Thank you for having me. I’m excited to be here as well.
hannah_went:
Yeah, and I always like to start off by you now learning a little bit about you. Of course, I have my little introduction that that I gave. but for those listening, can you just tell us a little bit about your journey? You know, how did you become interested? vial statistics and genetics? You know, your currently getting your Ph. D. so, even maybe for people who are listening and thinking about going into this space, you know what type of advice would you give them? All of the above.
kristen_mcgreevy:
Yeah, so I think my trajectory into where I am is relatively linear. I was fortunate to find what I liked in high school, so I, my one friend, told me that they could increase their odds of winning a raffle by folding their ticket, and I thought, wait a minute. I need to know this because the pizza raffles coming up. So I did a status experiment I high school to figure that out, and that was kind of when I realized that bio statistics or statistics is the best tool to answer our research questions, And then I had more Exposure to that an undergrad when I worked in a wet lave, Um, and I realized that being at a bench all day long is a little bit difficult, especially when you’re going to be focusing on one protein at one cell membrane for years of your life, And so I found biostatistics as the best avenue for me to understand research and to explore what’s happening with the data. And then when I was going into grad school, I knew I loved epogenetic sense, So I was teaching genetics and undergrad and I loved Epigenetics. I thought it was the new version of genetics. Really, Where it’s the modification of our geno, and we can change things based on our environment or habits. And so I found Steve, See for both, and I found his research and I thought why this is amazing. I’m going go to California. I’m going to do my grad studies that us, and hopefully work with him. And so I came out here. That’s ultimately the story that arose, And that’s that’s why I’m staying. I started working with Steve for my masters And that went well. So then I decided to state for my Ph. D.
hannah_went:
I love that you. You knew it, you wanted you went after it. You got it. So you’re right. That’s such a liner path, but such a great story. And where are you from? Where did you move from to go to California?
kristen_mcgreevy:
Yeah, so I grew up in Pittsburgh, and then I did my undergrad in North Carolina, so ultimately I moved from either one of those areas. Really out here
hannah_went:
Yeah, okay, Gotha. And do you remember when was the first time you were taught Epi genetics in school? Do you do you ever remember like I think back, and I think maybe it was like one sentence in my text book and under graded and that was it?
kristen_mcgreevy:
It, you know, I think it was kind of similar where it was in my genetics class. It was towards the end of the quarter and they brought up this idea of epigenetics and an metholation, and I was just blown away by it so immediately I went to the text book and I started doing all my research that I could, because I thought it was just the most interesting thing that we could modify how the geno was actually going to be read. And yeah, I agree, it wasn’t extremely well taught, so you had to go Find these other resources.
hannah_went:
Yeah, I was just just curious. I think Yeah, people have a similar history with with P. genetics in terms of just like their normal routine schooling that that they attended, and interesting that you, you liked bio statistics from the beginning as well, because I always say I just have a you know biology undergrad degree, But if if I could go back and do it all again, I would have definitely gone into computer science or computer training in the bio statistics, and because those wet labs become very repetitive or studious That eventual day, which is what I, what I did.
kristen_mcgreevy:
M
hannah_went:
so yet jumping right into it. You know, you have an amazing paper that was just published. This is perfect timing for for our our interview, But this paper is titled Dan, a Mmetholatian fit age, So to biological age indicator, and corporating physical fitness. So that is really what we’re going to dive into, But I first want to start just with the discussion of a physical fitness and relating that to You know, epigenetic. So you know, how do you define physical fitness in your paper? And why is this important to genetics? And you can relate it back to Gen? Of course, too.
kristen_mcgreevy:
Right. Well, thank you for saying it’s a great paper. I appreciate that a lot. so I think there’s typically five classical areas of physical fitness. One is the body composition, another’s flexibility than we also have strength. We have muscle endurance, and then cardiorespiratory endurance, and I think most well known within those tends to be strength and endurance, Because we think about strength training and we think about endurance training. I think that Physical fitness is a combination of all of those, and so you need to have a little bit of all of these different measures of fitness in order to be very fit and physically fit. and so flexibility I think is pretty. you know, general. So it’s how much movement you can have, and we know that this movement decreases as you get older, So range of motion and mobility, body composition is more so about how you have fat or muscle or bone distributed across your body and calm Ly. We think of that being measured through B, M. I. But what’s very informative is where that fat is distributed in soadominal fat, and seeing that that changes as we age, and that exercise itself is very important for this, and that if you exercise, you can actually decrease the abdominal fat specifically and have better body composition relationship to these aging, aging peno types, And then muscular endurance is really ability to contract a muscle pretty simple Repeatedly, and then cardiorestpiratory fitness is your lungs, your heart. all of that working together in order to provide oxygen to your body. And then I think strength is pretty straight forward. It’s you know this force. It’s you know, we see that lack of exercise is significant respect for a lot of different things, and that we see that strength is extremely important, for you know, long term longevity, and so physical fitness generally, as you know, declines with aging, and that People who preserve fitness as the age are at a lower risk of a lot of different diseases, and tend to live longer and healthier lives. And then we see that these changes in fitness seem to relate to these molecular processes, So you mentioned that at the end how it starts to be related to the Gnu. So we see these differences in athletes versus controls in what the Dnmathalatian patterns are. And we also see that there seems to be this long term effect that is accumulated in the p G From a lifelong time of exercise.
hannah_went:
Sure. Sure, and you know what I do when in my daily job is worked with a lot of health care providers, and you know, trying to talk to them about recommendations for having a healthy epigynom, you could say, and
kristen_mcgreevy:
Hm,
hannah_went:
we always bring up physical fitness. But that one is a little hard to talk about, because I would say the researches is still limited behind it. That’s why I love you or paper so much. So you just named those five areas of physical fitness. Would you say one is more important than the other, or would you? Prior to time? One over the other
kristen_mcgreevy:
Um, Well, I think if I was going to choose one, it’s going to be a relatively biased answer because I’ve been a runner my entire life, and so I think that’s part of my influence, but I also am basing my answer based on this research. So a lot of research has looked more more at endurance and strength, and I see that strength training especially for women is extremely beneficial, so I would say having women do more weight training that way Increase their longevity and health substantially, and then endurance is also very much looked at, and that seems to have a M. in my opinion, a stronger effect on these biological changes, so both of those having good endurance and good strength, I think are very high priority. but there’s also a lot of research that looks at more of this mobility and flexibility as being this good indicator of how you’re going to respond to this Interventions later in life, or that’s very much related to congshipdecline, having your durance firing, and you know frequency, so there’s a lot of different parts to which one I might prefer, but I think over all, I would say strength and endurance are my top picks.
hannah_went:
Got my mind went to the strength. Of course, I’m a weight lifter and getting more into
kristen_mcgreevy:
Hm.
hannah_went:
running, which is exciting because I used to run a lot and play play a lot of sports. but I definitely need to work on more of like the flexibility and mobility.
kristen_mcgreevy:
I
hannah_went:
Um,
kristen_mcgreevy:
think that’s all
hannah_went:
and
kristen_mcgreevy:
of
hannah_went:
trying.
kristen_mcgreevy:
us runners.
hannah_went:
Yeah, yeah, I definitely like the hot yoga. You’re like. Why am I doing this or wasting my time? But it’s so important as well, so I think just you’re right. You know a nice healthy balance and there’s research really with the endurance and Strength, but more to come on, the flexibility and mobility. so we’ll see. Um,
kristen_mcgreevy:
Hm.
hannah_went:
So I always love hearing how papers like this come to fruition. Love hearing the background on them. You know what questions were being asked in the lab when you were first creating the paper, and in your paper you even mentioned there are. Are you know? three lines of evidence that support a focus on on de metholation to develop vio markers of fitness, and in these age related changes and fitness. So I want to elaborate on that Prompted to build. You know, these Dnmethalatian estimates of fitness parameters.
kristen_mcgreevy:
Yeah, so I think it first started from us observing that many of our Dan Metholetian bio markers that we were using didn’t seem to perform as well as expected in athletes or people who had long term exercise regimes, so we were a little surprised to see that we weren’t seeing such a strong signal in these bio markers because these people we know to be healthier And so then we started thinking well. Why is this happening? In? Other researchers have demonstrated this as well That we do Don’t really see this benefit or difference in athletes versus other people until about the age of six years older. But we can physically see all of these differences at a younger age point. so we started thinking well. Ultimately, what can we build in order to distinguish this difference And you know, notice it at an earlier time point. And so we first said Okay, We know that Dnmetholation changes as we aged. You know, we’ve had so many different bio markers built from that. And so we’ve had these High precision algrithums especially for aging, which are also the epigenetic clocks. So that was part one. We know Da messolation is changing. that that would be good for some type of aging vio marker. And then we also know that epigenetic clocks have been improved by incorporating physiological data, So for example, we have penoagegrimage, et cetera that incorporate the smoking pack years, blood cell counts, plasma proteins into Prediction, algrithms, so incorporating some other aspect of somebody’s health is good for predicting these age related conditions, and so that would suggest that physical fitness would be a very natural incorporated into these Dnmethlatian bio markers, but none of the current bio markers included them. And then the last part of this is well, We also know that there’s this emerging evidence that these epigendclocks are sensitive to the life style factors, so you can Prove your epgnum and we also see that differences in your fitness parameters are reflected in the dnmmethalation data. And so we start to have this growing body of evidence that blood dnmmetholation carries information related to physical fitness. So we wanted to see. Could we actually build some type of bio marker fitness through blood dnmmethalation which you know. Really, We don’t even know. We didn’t think that there would be a strong signal because it’s blood, And
hannah_went:
Really?
kristen_mcgreevy:
yeah,
hannah_went:
Yeah,
kristen_mcgreevy:
well, because fitness you would think might be more related to any of your other organs, such as you know, muscle, or even add a post. but we are able to see a signal in blood, which was surprising. It’s not a. you know, an enormous signal. It’s not like our correlations are one. But we still do pick up a signal and it relates to a bunch of different outcomes.
hannah_went:
Yeah, interesting. yeah, but you’re you’re right. Once you really think about it you, you may not hypothesis that you would see a signal in blood, and maybe different, You know, muscle tissue or something of the sort. So yeah, that was. that was a good point.
kristen_mcgreevy:
Thank you.
hannah_went:
Um, and you just mentioned you use blood methalatian via markers,
kristen_mcgreevy:
Hm.
hannah_went:
so hopefully everyone listening knows why blood so important to use when looking at these these genetic clocks. I’ve addressed that with people my my previous interviews, so we’re going to skip over that point. Um, but you look at these bialemarkers of four fitness perameter, So you have your your gate speed, which is your walking speed, your hand grip strength, your forced experatory volume, and in one second and maxima oxygen, uptakrorvio, to Max, measure cardioreciprtory fitness. That’s correct, right, Those four markers
kristen_mcgreevy:
Yes, Exactly
hannah_went:
Perfect and this is something you know I’ve been very curious about. So why did you choose those for methalation fitness biot markers? And then you know you can go into them a little bit in depth. Maybe tell our listeners a little bit about what each of those mean.
kristen_mcgreevy:
Sure. So when we were choosing these, we needed to balance three different factors. One was measuring physical fitness across the different areas of fitness. So we talked about all of those five different main areas and then the other part is well. Can we choose these fitness parameters that are well researched and that we know to be associated with aging and age related outcome, so narrowing down what measurements we can take, a fitness that we also know relating to aging, and then the last That we had a factor in is well, we need to build a bio marker of fitness measures that have not been developed yet, so we need to provide something that’s new to the field. And so we balanced all of those and we also were you know, limited by what we had available in the data sets, but we had a lot of data set, so thankfully we weren’t super limited and so we ended up choosing those four bio markers like you, like you mentioned. So gate speed grip strength for Ceexpertory volume one, v one and v Max, So gate speed walking speed, It’s really a measure of this mobility and we see that it’s a combination of flexibility and this lower limb strength, so it’s really capturing two different parts of our fitness. This flexibility aspect, and then this strength aspect, Handgrip strength is very well researched and we see that if you have muscle weakness or weak rip strength, you have accelerated biological age. It’s also related very much to just maxima. Bet. Press is just like a cool side part about physical fitness. And then we also see that it’s related to premature aging, more mortality, disability, et cetera, So we knew group strength was going to be important, and that’s very much just a measure of that muscular strength. F. V. One is a measure of lung function, Amount of air that you can force from your lungs in one second, and people say that it’s more so a measure of this plasticity and your diofram, and that It’s related to your course stability. Um, and it measures really how much you can move in and out of your lungs at a time, And so that’s going to very much relate to how much oxygen you can get throughout your body when you’re exercising Vio, to Max, I think is my favorite measure. so it’s your maximum oxygen consumption. It’s really a measure of your cardiovascular or Cardi respiratory health and your robic endurance. So it’s the amount of oxygen or Volume of oxygen that your body processes with incremental exercise, and ultimately this is considered one of the best indicators of an athlete’s physical capacity, and it’s the international standard for physical capacity. So we see that votumax is really you, quite important, and we see this routine last related to aging vino types. That this will decline over time, but people who exercise seem to preserve votumax and have these better outcome. S.
hannah_went:
Why is that when your favorite have to know?
kristen_mcgreevy:
I think ultimately it’s it’s harder to measure, but I think that it gives you a very good idea of your intrinsic fitness from this measure of you’re taking into account your heart, but you also have to be able to do this exercise in order to take the vio to max measurement, because you’re going into harder and harder exercise as you’re doing it, and people
hannah_went:
Hm,
kristen_mcgreevy:
who are much older sometimes they can’t take this vio to Max measurement because it’s not Because you’re going into harder exerciser gems. And so you get to really see this transition of how you’re starting from the beginning, how you’re going up, So you can also relate this to. well, how am I feeling? You have a heart rate that’s lower in the beginning, but then after a couple of minutes you’re like Wow, I’m super fatigued and so viotumax is really. I think a good measurement to say. Well, can you even do this type of exercise? Do you have the strength O the flexibility of the mobility? And then how
hannah_went:
Yeah,
kristen_mcgreevy:
well can you do it? How long?
hannah_went:
Gotcha isn’t it You put on like a mask and your you’re on a treadmill. Is that correct? Yeah?
kristen_mcgreevy:
Yeah,
hannah_went:
okay,
kristen_mcgreevy:
so that’s
hannah_went:
I know
kristen_mcgreevy:
that’s a very common way.
hannah_went:
Okay
kristen_mcgreevy:
Yeah,
hannah_went:
and there are other ways maybe to measure it too.
kristen_mcgreevy:
Yeah, so there’s another way. I mean, it’s very similar to that. You can also be on a bike. And then there’s also another one which is called the chest or step test, where you’re really going up and downstairs And then if you don’t have any way to do physical test itself, then there is some type of conversion between your heart rate and know these other variables, But that’s not as good as a signal because that’s very much dependent on a lot of different factors. It’s not The best measure of your tum. The best ones are exactly what you’re saying, wearing the mask running or wearing the mask, Viking,
hannah_went:
Yeah, I’ve never measured mine, so I’m super curious. Now I’m thinking If I even able to
kristen_mcgreevy:
Uh,
hannah_went:
would I be able
kristen_mcgreevy:
uh,
hannah_went:
to do it, but I be able to measure it. So yeah,
kristen_mcgreevy:
Hm,
hannah_went:
I’m going get that tested at. At some point.
kristen_mcgreevy:
M, hm,
hannah_went:
Were there any fitness prameters that you really wanted to include, But you didn’t have enough data on them or didn’t
kristen_mcgreevy:
M.
hannah_went:
make the cut. I know you said you were lucky with with what you had, But it was there something that you re like. Oh, it was just so close.
kristen_mcgreevy:
Yeah, you know, I think that’s you know. a great great question because ultimately I built a lot of bio markers in this process, So some of the bio markers that I built. I just didn’t have variables in the validation data sets, so I wasn’t able to see all these actually measuring what I want. So for instance, I also built a bio marker for the maximum distance that you could jump in height. And so that,
hannah_went:
Oh,
kristen_mcgreevy:
Yeah, so that would be a great market right because it’s You know its strength. it’s you know, maybe a little bit of flexibility, maybe a little bit of endurance, Since you’re taking that measurement so many times, and ultimately there was not very good variables to correlate that to to check in the validationdata set. So I mean, gate speed sure might be kind of related to jump Max, but at the end of the day, that wasn’t a strong enough relationship to say whether or not this was going to be informative, and then the other bio markers that I’ve um considered was a measure of body composition, so I didn’t talk about body composition in any of these Dan Methalatin fitness biomarkers, so I considered making one for B, M. I or this adiposity around the waist, didn’t have adiposity around the waist, so couldn’t look at that, And then there’s also methalagian bio markers for B. I already in using blood, and so ultimately I was thinking it might be better to build one using It was in metolation instead.
hannah_went:
Gotha. Yeah, very cool. that jump Max is super interesting. Bring it, brings me back to my track days in high school when I would do like the long jump and the
kristen_mcgreevy:
Exactly.
hannah_went:
long jumps. Not, I wasn’t very good at it by any means, but it was really fun. Just you know, seeing how long you, how far you could, you could jump. So so that’s super interesting and
kristen_mcgreevy:
Hm.
hannah_went:
to expand even further. You know what makes these biomarkers different from other Dan Methalatian bio markers?
kristen_mcgreevy:
Yeah, so I think the different dena metholation bia markers are incorporating different information or are measuring something different. So the Nita pace of aging. that’s very
hannah_went:
Hm,
kristen_mcgreevy:
much a measurement of how you’re aging is changing. so biological age and how that’s pace. Peno. Age is another one that it’s commonly looked at, which incorporates this phenotypic information. But it’s all type types of phenotypic information in the blood, So you have Roteins and blood sell information like albumen, glucose, lympasite, percentages, et cetera, and then grim age is a measurement also built in blood, but it’s measuring and incorporating these different plasma proteins and pack years, so measurement of how much people have been smoking, and so ultimately all of these different viomarkers haven’t incorporated this physical fitness component to them yet they are incorporating different parts of the blood or different parts of this. You know typic, Um, you know, relationship to somebody’s aging and their biological age, but they have an incorporated physical fitness and I think that’s ultimately what makes these ones And you know, the later part of this paper fit age more novel and distinct.
hannah_went:
Awesome. Yeah, now that’s that’s great. super unique insights that that you’re looking at here? Um, So you’re taking you know you now have these Dnmethalatian bio markers to predict at speed your grip strength, the p v one in the vio to Max. So you have kind of these segregated clocks right? You could call
kristen_mcgreevy:
M.
hannah_went:
them genetic clocks for for this fitness, but you’re using than these bio markers to develop this very novel Dan Metholatian, fitness related biological agent indicator. So you know the title of your paper, the Dnmethalation Fit age, and this is really quatifying the relationship between physical fitness and biological aging processes. So can you explain this? What’s what’s the An methalation fit age?
kristen_mcgreevy:
Yeah, absolutely. and what you said is exactly right. So we first are introducing these Dan, a metholation fitness bio markers, and then we’re combining them to get an estimate of somebody’s biological age from this perception of physical fitness. So we are incorporating three of our fitness bio markers. We include gate speed grip, Max and voto Max. We excluded V one, because when we looked at the different models in the end it didn’t really seem to improve Things as much. So we just took the parsimonious model, And so we’re incorporating those three fitness perameters along with grim age, the mortality risk estimate, and we’re combining those through the method Camera Do Ball, and all of this together comes up with a biological age estimate. So this fit age is really a biological age incorporating strength mobility and cardio respiratory fitness.
hannah_went:
Just taking some notes here as where we’re chatting. It’s super
kristen_mcgreevy:
Yeah,
hannah_went:
interesting and I want to talk about the population you use. So what population or cohorts did you use to? Actually, I don’t know if they were different when you created. You know the four clocks and then the Dnmmethalation fit Age. Or can you talk about that?
kristen_mcgreevy:
Yeah. sure, so we used three data sets in the training part of this. So the Framingham Heart study, F, S, and Baltimore Longitudinal study of aging, B, l, S. A. And then we also had a novel study which is Budapest, which are my co first authors. Old Radack had now collected all of this data in Budapest on these long term rowing athletes and control. so these people are all performed in this rolling work, Ada, at some point in their life, So they’re like very, very good rolling athletes. And then there’s like these controls who wear age and sex matched, So we used those three different data sets to combine them into a training set. So the Framingham heart study is no study of your heart. It was. It’s a very well studied population. A lot of different Vio markers have been developed using this and it’s a large data said, so Over a thousand people in it, Baltimore Longitudinal Study of aging. We have multiple time points on people, so ultimately we’re just using that first measurement so that we’re not getting an increase of the correlation. But all of these people are generally healthy in the F s and the l, s. A. And then we have that novel fitness component in the athlete part from the Budapest. So those were all their training data sets, And then our validation data sets ranged as well. So we, we looked in Calory, we looked in Women’s Health Initiative we have in Canty, We looked A lot of different ones, including the Lothian birth cohorts, so over all we had, I believe six validation data sets that we were looking at how these different fino types related to our fitness bio markers, and ultimately this estimate of biological age.
hannah_went:
Sure, Sure that Ud Budapest cohort you mentions Um, super interesting. Are there a lot of cohorts of athletes like that or is that hard and typical to fine?
kristen_mcgreevy:
It’s very hard to find.
hannah_went:
Uh,
kristen_mcgreevy:
it’s It’s quite sad, but ultimately most of the studies people aren’t going to be these extreme athletes. so I think typically these clinical trials or these studies are trying to enroll healthier people that aren’t like super
hannah_went:
Hm,
kristen_mcgreevy:
healthy, or too far from the norm, And so it was actually very difficult to collect these data and to get something like that. Even if you go on to go to look for These different data basis, it was hard to find athletes that also had data methalatian taken, because typically when people are looking at athletes, they’re more inclined to say Well, what’s their recovery period or how how fast are they going to be? How much longer do they have to be in the sport? They’re more so
hannah_went:
Hm,
kristen_mcgreevy:
focused on these other variables, not necessarily biological age, because they already know their fit. they already know that they’re healthy. They don’t really need These type of measurements, so it was hard to get, and interestingly, um, next year we’re going to have data while my collaborators are going to have a data set that they are fortunate and very kind to let me share where they are sampling eighty gold Olympic medalist and then age and sex matched controls. And so they’re looking at Dan Methulation, and that will be very exciting.
hannah_went:
Okay, yeah, that’s super interesting. We’re gonna have to chat more of out that off line. I’m super interested in hearing a little bit more of that, but like you said, there’s you know, Not really much we we know or can look at as it relates to Dnmethalation. so I think that will just be a huge value to everyone doing research in the space and knowing those those specific outcomes. So that sounds extremely exciting.
kristen_mcgreevy:
Hm.
hannah_went:
Um, and leading off, you know what’s the application of Dan methalation fit age? I don’t know if it’s better To ask you now. how is that actually related to athletes or physical activity and different age relating related pena types?
kristen_mcgreevy:
Yeah, so I think that there’s two main things that fit age has been shown in the paper. At least to relate to one. is this age related, peno types, and then physical fitness in the expected directions. So what we first did is built this age adjusted version of fit age. So we’re calling that Fit age acceleration. And as you know, it’s pretty common to just talk about age acceleration value, So really help D. V. You are from your expected age and so positive values tend to be bad, because that means you’d be older than expected, and negative values are good. And so we use this age adjusted version and then we look at how that relates to a variety of things, and we see that it is predictive of mortality, coronary heart disease, Um, and we also see is related to earlier age of mental pause. More comorbidities. All of those were, if you had a Larger fit age or a higher age acceleration, you had an increased risk for that. And so if I, I’ll just give you one example mortality, We had a hazard ratio of one point seven. And so that means that if you have a ten year acceleration in fit age, that corresponds to an almost doubling of your mortality risk compared to some one of the same age and sex. And so that just shows that fit age seems to be related to some of these age related conditions, And then the opposite was also true, where if you Had a better fit age or younger age acceleration than you had better outcome. so you are associated with disease free status and lower collesteral. And so all of that is really showing that. Okay, we see that fit age is related to these aging outcomes, And it seems that if you are fitter than you have better age related, you know types. and then we also saw for the fitness part of you that if you were more physically Then you had a younger fit age, and this was true in both men and women, so we saw that if you looked at people with just intermediate amount of exercise compared to people who had none, we were able to see that just a small amount of physical activity really was improving your fit age, and then also these individual fitness biomorkers. It wasn’t a huge increase. We say, See like a point three, three year d Crease. So your age acceleration point through three years decreased with just a change from zero to load intermediate physical activity levels. But then we also looked in a sample of body builders, so we were able to find Polish collaborators who had sampled body builders and Dnamethulation and we saw that body builders were biologically younger and more physically fit, so their fit age value on average was two point seven Younger in the male body builders compared to controls. And so you know that’s great. And then we also saw that Dnmethelation vio to max was point for mill leaders per killagram per second better in these bodrybuildes as well, so we are able to see those relationship to physical fitness in these athletes. So the body builders, but then also in just regular people in our valid ation data sets, So valid ation data sets didn’t have athletes in them. We saw that if people had just a slight increase in their physical activity level, then you had better outcomes.
hannah_went:
That’s very promising. It makes you you know, want to go work out? I already worked out this morning, but makes me
kristen_mcgreevy:
Hm.
hannah_went:
feel guilty now for skipping
kristen_mcgreevy:
Oh
hannah_went:
some days. so even just you know, a little bit of movement is really great. Am I correct? An, maybe making that conclusion.
kristen_mcgreevy:
Yeah, and I think that we are starting to have more research that shows just even marginal, Very slight increases in your physical activity really have large effects where I don’t remember what the study was, but I, I remember that within it they only had a one day a week increase in physical activity, so they said, Just do one more day a week physical activity and they were able to see in people who were starting at zero exercise and improvement of their biomorkersso. I think that ultimately what we’re starting to see is that just even a moderate amount of exercise is super beneficial for your health.
hannah_went:
Yeah, I think that’s super hopeful as well, right because it’s it’s you get in this routine and maybe you fall off the routine and it’s really hard to get back into the
kristen_mcgreevy:
Yes,
hannah_went:
routine when once you’re off it, I know, at least personally, I feel that way, so it just pushes that point further that just a little bit goes a long way. You know, recently, a couple of changes that I made is, I felt just like I was sitting all day and I wanted to move a little bit more. I only took like a fifteen minute walk from my. You know, I’m working nine to five. Um, and you know that just seems ridiculous, So I, actually, I took the initiative, got stand up desk and then got one of those walking pads to go underneath of it and I thought I’d be a lot harder than it actually seems, And it’s great. I’m getting in now. a ton more steps. I can’t stand sitting down all day now. I just want to be standing up. I remember on the way to work hearing something on the radio that said Like sitting is the new smoking And that’s what. Really why I started looking into it. Yeah, so I think we’ll see a big shift and in trend toward you know more of that healpthly living. Hopefully right, because at least in especially here in the states where very stressed out, we’re very know, sedentary we. We’re not getting in a lot of movement. so just that that hopeful piece to hold on to that just a little bit actually goes a long way. I think you now, great silver lining.
kristen_mcgreevy:
Yeah, I completely agree, and just another thing that I think is interesting. I’m going to share through that we learned through this research. Is that you mentioned that it’s hard for you to get back into exercise afterwards. You know, when you have this, you know period off, and I think that’s true for a lot of people. But then what we also are able to see even at the epigenetic level is that people who are you know, exercise our athletes for a long period of time. If you have this short Amount of time may be a few months that you’re not exercising. It’s a lot easier for you to get back into it and get to your max or where you were before, rather than somebody who would just be starting at what your level was at that time period where you’re resuming exercise. And so this curve of how long it takes you to get back is really shortened and abbreviated for preople who were athletes were exercising previously, and they say that this is from this epigenetic memory. And so there seems to be a signal that Restored and retained in your dnmethalation or other epigenetic components that translate to you getting back to your peak exercise performance quicker after a period of rest.
hannah_went:
That’s very interesting. Yeah, because like mentally, it’s hard for me to get back up and get in the gym. But actually, once I’m in the gym after I’ve taken like a couple day break or even a week or so, I don’t know if I’m like on vacation and not in my normal routine. I do almost feel like a little bit stronger, and
kristen_mcgreevy:
Yeah,
hannah_went:
like I didn’t lose a lot of that muscle memory. I actually do because I think also our bodies need breaks right. We can’t be in an go go mode all the time, so that’s interesting. Yeah,
kristen_mcgreevy:
Hm,
hannah_went:
I find that to be true for me, At least
kristen_mcgreevy:
Yeah, and I found it to be true for me as well. I had a
hannah_went:
Hm.
kristen_mcgreevy:
concussion earlier this last year, and I was out for two months of exercising and I, you know, would exercise, you know, four or five days a week, and I noticed that Onth I got back into it very quick, and that was I had the same experience. Was like Wow, muscle memory. I was able to get back here so quickly and then I had a conversation with our collaborators and they started to share this with me. So then I started doing a little bit of re Search into it, and thankfully the research back my experience, which was, I was able to get back into my peak performance quickly even after taking two months off.
hannah_went:
It’s a real thing like a genetic muscle muscle memory, so I’ll keep that in mind next time again you feel guilty for taking a break or taking days off.
kristen_mcgreevy:
Hm.
hannah_went:
Christen, Is there anything else you? You want to add? anything that these bio markers contribute to the field of agin, An epigeneticas. I know you’ve They contribute a lot. we’ve already talked about, but anything else?
kristen_mcgreevy:
Yeah, I mean, I think really, I see them as providing a physical fitness component to our epigenetic clocks and being able to show that our blood epgenum changes to a company physical fitness. and so I think that this is really what their providing. It’s giving us a molecular understanding of the exercise benefits and that hopefully these will allow us to see more of a difference in athletic populations An earlier age, instead of having to wait for around age sixty to see these benefits of exercise really kicking it, so hopefully we’ll be able to see these as tools to either measure interventions, you know, exercise based regimes, or then also be able to distinguish athletes versus other people at earlier time points to actually show that there is some type of difference biologically.
hannah_went:
Sure? Sure, and how can we actually trust that the Dnmethalatian fit age is a bio marker of agen?
kristen_mcgreevy:
Yeah, I think it comes down to how you view what aging is. So I think if you people have different theories of aging and ultimately fit age is built on two main requirements, So in order to build this, I mentioned the clemaradubalt method, And so, in order to use this method, you first have to say Well, we believe that biological age is centered on chronological age, so that means that if we sampled everybody who is Ronologically aged sixty, and the population, the average of their biological age would be sixty. And so, if we just believe that biological age is centered on chronological age, and that we have deviations from that, That’s one one part, and then the other part is that our bio markers that were measuring, so these different fitness bio markers are actually functions of biological age. That they’re changing with biological age, and that biological age is actually the predictor and can be used To estimate the biological age, the bio marker itself, And so those are two of the requirements when we’re building our models. And so if you believe that those two things are true, then ultimately you can start to believe that the methods that we used to build fit age are valid, and so one is just saying Okay, I trust these methods and I accept this, these requirements of biological age to build this. But then the next part, I think the trust comes down to. Well, do you Believe that things are related to aging if we see a relationship to age related peno types, which is everything that I’ve been able to observe so far, So you know, we looked at mortality, we looked at type to diabetes, menopause, cancer, collestral, disease, free, status, et cetera, And we see that all of these are related in the expected direction, but we haven’t been able to explore other aspects of aging, So you know we didn’t look specifically at these different inflammation markers, or you know senescence. So if you Have a different theory of aging, then maybe you wouldn’t believe it or something, but at this point it just hasn’t been validated in those steps, so I think Yeah, in some rat, I think it just comes down to. Do you believe in the the assumptions of requirements when we built it? And do you think that aging can be well summarized with the relationship to age related funeral types?
hannah_went:
I think that’s just an important question right when we should ask. You know all of all of the researchers who re creating these papers and different insights into aging. Because like you said, it varies from from person to person and kind of their methodologies that they use in Agin is just so complex.
kristen_mcgreevy:
Hm,
hannah_went:
So re learning more as people like yourself and other researchers are diving into these experience experiments.
kristen_mcgreevy:
Hm,
hannah_went:
Um, and we’re almost getting to to the end there. but A couple more questions. You know, I think I say this all the time. Genetic is extremely exciting, but I think it’s equally frustrating because it’s so new. There’s a lot that we don’t know. Um, So what do we not know about these biomarkers? You know, what wouldn’t they tell us?
kristen_mcgreevy:
Yeah, so right now we haven’t been able to evaluate them in a much younger population, so most of the time when we think of athletes, we think of people who are you know. Maybe you know like eighteen to like twenty five. You know a small range. We think of them as being pretty young people, and we haven’t been able to evaluate them in a super young population. So one is what we need to go to younger people And see, Is this something that validates at a younger age frame because we’re able to It in these lifelong athletes are people who have been athletes for a long period of time, And so we have in that regard more time to modify your Etbginum, So we need to see how it performs in a younger population, But then we also haven’t seen how it performs based on fitness interventions. So if somebody goes into an exercise regime, can we see in three, six throe or six months, maybe even a year, a change in these biomarkers we don’t know yet, So ultimately I would say those are the two biggest limitations as well. How does it perform in younger people? And do we know if this is going to be modified based on exercise?
hannah_went:
Sure, Sure, great points, and I’m sure we’ll find out you know the answers to those questions again. As we build from this, this type of an amazing amazing work that you’ve done. So you, you have this paper. It’s finally published. What are you focusing on? Now? you know what other research are you conducting? Are you adding on top of this switching years?
kristen_mcgreevy:
Yeah, so I am in a few different projects. One I mentioned earlier is looking at these gold olympic medalist and control, so I think that would be quite interesting to see how the epginom is changing There. There’s other projects that also might be quite interesting to your listeners, So I’m looking at Dan metolation in muscle and a post issue in the calory study, which was the clinical trial that A restricted their caloric intake by twenty five percent for two years, And so I’m looking at not just how Dnmesilation is changing, but also how your base line d n mesilation is predictive of your responsiveness to the treatment. So you know we have caloric restriction, and that if you restrict your calories, you will lose weight. That’s just you know the science behind it, But then you stop losing weight at some point because you adjust your B, M. and so seeing what that responsiveness is We’re hoping is going to be predictive of what your base line danmetolation is, and then seeing well if you can improve that based on some other life style trait, So I think that’s you know, the other component that’s quite interesting. And then I’m still finishing my dissertation and so I’m also improving, trying to improve imputation of Dan Metholation by using a transformation procedure which hopefully I will be able to share with all researchers similar to health. All of these biomarkers are available to
hannah_went:
Awesome? Yeah, thanks for that, Chris, and sounds like you are doing a lot of different projects that are super excited. An I’m goin to have to have you back on here a little
kristen_mcgreevy:
Hm.
hannah_went:
bit more about that once we were able to. Um, so now this has been great. I really appreciate you. you’ve being on giving us your expert to use knowledge in this field. One question I asked everyone at the end it’s a curve ball question. M. Christian, If you could be any animal in the world, what would you be and why?
kristen_mcgreevy:
Oh, okay, Well,
hannah_went:
Just a little fun. one?
kristen_mcgreevy:
you know, I think I think any time that we try to say what animal we want to be, we want to be at the top of the food chain somewhere, because we’re afraid of like other animals trying to eat us. And so you know, a super simple, probably predictable answer would be like a hawk or something, because you want to be at the top of the food chain, And also, I think everybody really wants to fly, so that I used to think I wanted A dolphin, but I realized that being in the ocean is actually kind of scary, so
hannah_went:
Yeah,
kristen_mcgreevy:
not a dolphin anymore.
hannah_went:
There you go. Well, it seems like you’ve thought about the question before and then you have reasoning too to be at the top of
kristen_mcgreevy:
Oh
hannah_went:
the food chain. So I love it. Now we’ve come to the end of this amazing podcast interview for listeners who want to connect. You know where? where can they find you? How can researchers access this this information or you know these algrythms If they want to look at other vile markers or insights with their data,
kristen_mcgreevy:
Yeah, so you can connect with me on Linked in, you know, I’m Christine
hannah_went:
M
kristen_mcgreevy:
Mcgreevy. You search me and that will come up. I’m also, you know on Instagram, Twitter, et cetera, So whatever avenue people really want to contact me, they can email. Also find Christ in May at us, Dot, and then to get all of these different bio markers, I have all of the code and functions to use them on Get hub. So if you go to get hub, you get hubs dot com slash Christine, Mc Greevy, slash d, M. fit age, you’ll find all of the code and you know programs in order to make these biomorkers yourself, as long as you have Dnmethalation data, and then the paper, as you mentioned is published in aging Albany, So if people want to read the manuscript themselves, you know they can go there.
hannah_went:
Perfect and I’ll make sure I’ll put all of that and in the show note so people know where to find you In there. they’re able to access your your great work. So M. thank you again, Christen, I really appreciate your time things for for everyone listening and joining the Everything Epigenetics Podcast. Remember you have control over your Dan regulation and epgenetic, so tune next time to learn more. Thanks so much, Christine.
kristen_mcgreevy:
Yeah, thank you, Hannah, thank you so much for having me.
