Unraveling the Complexity of Epigenetics in the Brain

welcome to the everything epigenetics podcast where we discuss DNA regulation in the insights it can tell you about

your health I’m Hannah Wendt and I’m the founder of everything epigenetics today my guest is

Dr Esther Walton our main subject today is going to be neuroimaging and

epigenetics we’re going to talk about Dr Walton’s background and why she chose to study the brain we’re also going to chat about

what TNA methylation measured in blood it can tell us about the brain and how

strongly mental health is linked to physical health and what rural epigenetics plays in this Association

we’ll be talking about a specific measurement Dr Walton has studied called the brain age and how that is created

and how it is associated with epigenetic aging we’ll also dive into developmental

timing what she means by saying aging starts at Birth and why it’s important to look at the relationship between

methylation early life stress the brain and mental health and certain associations that appear and disappear

at different life stage life stages a quick introduction into my guest Dr

Walton’s research focuses on the links between early life stress epigenetics brain structure and mental health

as an associate professor in Clinical Psychology at the University of bath in the UK her research on health traits

includes depression ADHD schizophrenia and eating disorders and often consider these in the context

of neuroimaging and physical health comorbidities such as faster aging and cardiovascular diseases

she has a hands-on experience leading large-scale collaborations and has also co-established the international

methylation Imaging and neurodevelopment or mind Consortium to shed light on the

relationship between epigenetic patterns and brain structure across Child Development we’ll talk about her

Consortium today as well she was an active member and the lead on several projects within the

international enhancing Imaging genetics through meta-analysis the Enigma Consortium and the largest Consortium to

understand brain structure function and disease based on brain Imaging and epigenetic data

and now for my guest Dr Esther Walton welcome to the everything epigenetics

podcast Dr Walton I’m excited to have you today yeah yeah so you’re really an expert on

epigenetics in the brain and really excited to dig into this a little bit further I know that’s going to be the main focus of our chat today but I’m

excited to have you on in particular because little is known about the extent to which DNA methylation is linked to

individual differences in the actual brain itself and I think a lot of the listeners will be ready to really dive

into this as well so you know how these associations May unfold over time across

development and there’s a time of life when many of these disorders emerge within the brain itself so before we

actually start to talk about that further and unfold that you know why the

brain why why are you studying it out of all kinds of organs it’s a very complex one what what started your journey into

this amazing field uh well you’re right the brain is amazing

um my journey well I suppose it’s uh as as often happens a little bit more complex and more in a roundabout way uh

so I I was in a way always interested in the brain more from a new science

perspective than from a psychological one um but as probably my my schoolmates and

my teachers can attest I wasn’t the most motivated student in biology in high school I was always in the back a little

and when it came to going to University I was a bit undecided and I thought

about you know maybe medicine or maybe psychology but also I thought about going into languages or maybe music

so I ended up going to or I signed up to this broad undergrad program in the

Netherlands where you could take all sorts of different courses so that was a course on history and of course a few

courses on psychology but also biochemistry and criminology and it

wasn’t until the end of those undergrad studies that I thought like well actually medical legal science is really cool you know this is this is fantastic

and then I I got onto a master program in Germany on medical Neuroscience but I

didn’t get into new Imaging until the end of that program and

um and then I didn’t get into Imaging genetics until my PhD and only at the

end of my PhD did I start working on epigenetic data so it really took a very

long time to get into into that area um where I’m working now but just to

answer your question about the brain um the the brain in a way is at the same

time amazingly complex but also not as complex as it should be so for example

there is this Urban myth that there are as many neurons in the remain as stars

in the Milky Way for example and we we now know that that’s not true you know they’re just over 80 billion neurons in

the brain which is still pretty impressive but it’s not as much as stars in the Milky Way

and there’s a lot already we know about the brain we know how neurons communicate we know how the brain

structure works and develops and we have mapped different brain regions but what we don’t understand still is the the

link between you know the the structure of the brain the stuff we can look at the stuff we can measure and how that

translates into our personalities our mind our mental well-being and when it

comes to the brain I think I suppose I in my research focus on on two things in particular the one being like is the

brain really the Standalone organ for our personality and our mental

well-being um so for example if you you know through some kind of weird sci-fi setup

or something we’re able to take the brain out of the body and attach it to some kind of you know weird device would

you still have the person there you know with all their quirks all their jokes and memories or do you need the

periphery for that right uh so we we know there’s for example that you know

gut brain access and you know some ideas that gut influences our mental health

and our personality so do we really need that ascending between physical and mental health

and the other thing that interests me is really what what shapes the brain so we we’ve been involved in a range of

studies describing the genetics of the brain uh and we we found that genetics

generally explains roughly around 30 of of great morphology but that leaves a

lot of space for environmental uh influences and Gene environment interactions and that’s really you know

where epigenetic comes in so how does epigenetics relate to to to the brain

itself yeah yeah that’s such an interesting story thank you for for sharing Dr wall and you know I can see

where your passion lies and I think it’s very promising for listeners out there you know you are interested in some of

the more maybe psychology a little bit during your undergrad not really maybe a little bit of an interest and then you

keep growing that and growing that and growing that I think especially here in the states we always feel rushed to

choose one thing and then make that one thing our life but it’s it’s beautiful that you’re able to grow that through

the work you’ve done in this field so far and I also appreciate you making something

that still is very much complex the brain itself but making it much more easy for users to understand that say

wait a second it’s actually simple and we’re starting to learn more and more about that so um yeah I I know I have my list of

questions here but that introduction just made me want to ask you know a lot of others especially highlighting those two others you know is it the is it the

only the brain where we’re getting a lot of these personality traits or you know like those quirks you mentioned and then what actually shapes the brain I think

one of the major questions I get from people the most is hey what part of the

body is genetic and you know definite and then what part can we actually change so that statistic that you also

gave hey you know 30 of um our brain is probably explained by some genetic

Factor it gives us 70 to discover to understand what epigenetics is doing to

the brain so let’s let’s really set the stage for our listeners here can you explain what

um you know epigenetics and you know the DNA modification DNA methylation in particular measured in blood can

actually tell us the brain what do we know so far about that 70 um uh well really good question so uh

it’s it’s quite a contested topic about you know can DNA methylation in peripheral tissue such that as the blood

really tell us something about the brain and you know I certainly had a few heated debates on that

and I think at first the message probably is always

um not not much you know generally uh the first impression is always uh that

you know you can’t make influences from blood-based methylation of the brain however I I come to that you know but uh

in a second um but but first so why does it look so difficult at the beginning

um the one thing being that DNA methylation is actually quite tissue and

cell type specific so if you gave me a methylation data set and you didn’t tell

me where it came from I could probably quite quickly tell you you know you got that from a brain sample or from a blood

sample and uh you know cell identity is really fundamental to DNA methylation

data so initially you would think well yeah that that makes sense so you know make the influences from one teacher to

another is probably a little bit more complex and to to describe that better

we did a study uh quite a while back already in 2016. where we looked at the correlation

between blood-based methylation and brain-based methylation and there have

been people who’ve done that before we did but what they usually did is they looked at postmortem brain tissue and

that comes usually with its own set of limitations or often in those studies blood Wars

um measured and the pre-mortem and then when people died and they donated their brains to science you know you could

measure DNA methylation signatures in postmodern brain tissue but you know those signatures might Decay a little

bit or might change with the post-mortem interval because you know it’s fundamentally dead tissue

so what we did differently in our study is that we looked at life brain tissue

and that’s exceptionally difficult to get hold of and so we got that tissue

from epilepsy patients who were undergoing brain surgery to remove the

part of their brain that is causing those epileptic seizures and you might say well you know uh well

that’s a huge limitation right because you’re looking pretty much at disease tissue but we made sure that we looked at DNA methylation profiles obtained

from from the outer edges of those brain tissues to get tissues as healthy enough

as possible and we obtain blood samples at the same time from those patients and

then we correlated those epigenetic markers now what we’ve found at the time was

quite in a way quite devastating and we found that actually only eight percent of methylation sites correlated

significantly across blood and brain tissue and they could have suggested well

actually we we can’t really use blood tissue to make any influences about the brain

but you know and now my my face but I I think uh

we can it works really well but we have to really honor the complexity of those

associations so for example what we find is that there’s a time delay at which um

associations emerge across tissues um and maybe to give you an example this

is completely unrelated but uh to their health you know understand this better I’m yes please I’m really bad at

gardening and at watering my plans even in the office okay and I never really

figured out how to do it properly and the problem I’m having with watering my plans is that I might forget today to

order my plans but I don’t get immediate feedback you know my plan doesn’t start watering today or doesn’t stop dying

today it starts dying in two weeks or maybe a month’s time but by that point in time I I can’t

quite remember what I did two weeks ago or something like that did I over water my plants that I underwater my plans so

if I just looked at a cross-sectional association between my watering skills and habits and my plant half I probably

wouldn’t find much and the same applies to epigenetic data

across tissues so it’s fair to assume that you know that signal there’s a

singer that does transmit across tissues but it takes time and we have to model

that that time delay in a better way and we have to understand that much better and there’s there’s evidence for uh you

know that those cross tissue signals should be linked because we know there’s a strong link between physical and

mental health and we know that a range of physical

um health problems such as increased inflammation is linked to um you know depression and schizophrenia

and we also know that there’s a metabolic component to eating disorders so we know there’s a link we just have

to find better ways of modeling it yeah yeah I love that that example that you

gave there you know I have a ton of plants at home and hey Green Space increase in Green Space actually has

some really good positive epigenetic outcomes as well right there’s a couple studies out there so um yeah no no I mean you broke that down

perfectly and I think yeah only time will tell and again like you said only eight percent of those DNA methylation

markers actually correlate across blood and brain tissue so we’re working with a very limited data set as well

um so I think it’ll be interesting to um look further at some of that post-morton brain tissue or even more I

guess you call it more of that live brain tissue I was actually just speaking with someone from Emory University outside of Atlanta Georgia

and they have a really good brain Bank along with University of Kentucky here because they’re doing a lot of work in

Alzheimer’s so to be able to have some of those Banks but again needing that live tissue is very much necessary so I

appreciate you highlighting that work in in 2016 that you you performed my next question you led me directly into that

um you mentioned it very briefly but if you want to add anything else Dr Walton please feel free um really how strongly is mental health

linked to physical health itself and then what role do we actually see epigenetics playing in that Association

sure um well um mental health and physical health can

we linked quite strongly and in combination they can have quite severe

Health outcomes so um for example they’re like excellent

studies coming out from from Denmark out of all places they have like this amazing data set up where they have uh

you know access to longitudinal Health Data from people across the lifespan or you know of course at least you know 10

or 20 years um and I think I think like across the whole population of Denmark so those are

really large data sets uh where you can um really describe the link between physical and mental health and how it

leads to you know how it impacts mortality for example and what those Studies have shown is that uh people

with mental health problems for example have reduced life expectancy of of four years I mean that was one particular

study that estimate differs depending on what data you look at and people with physical health problems have a reduced

life expectancy of six years however people with both physical and

mental health problems have a reduced life expectancy of 11 years so it’s quite a step change you know from from

four to six to all the way to 11 years uh suggesting that you know the uh

the intersection of physical and mental health problems can have huge impacts on on well-being in general so what we’ve

done in our research is to study the the the genetic and environment to predict

us for physical mental health for morbidity so for example we did a

genetic study looking at genetic markers predicting physical mental health comorbidities so we looked at people who

were ill with heart disease diabetes and depression

and we found this really strong genetic signal on chromosome Aid and that

replicated really well and there was one study and then on the other study we looked at the the reverse you know like

can we identify environmental risk predictors for multi-morbidity and here

we um we worked with you know collaborators and so we’re part of this early course

Consortium that’s like across European Consortium where we pull really large data sets across Europe to really study

this Across the Life Course and what we found for example is that a history of

childhood maltreatment is a strong predictor for physical mental health co-morbidity much more so than just

physical or just like poor physical or just poor mental health so it’s really

um causing or potentially causing physical men to have problems in

combination uh and then and now the logic next step

right after having found the genetic predictors and environmental predictors is to look like uh what are the

biological Pathways mediating this and we have identified a range of biological

Pathways both in the physical space such as increase BMI cortisol levels uh

insulin dysfunction as well as a few mental health behaviors like sleep

problems for example um and what we’re doing now is to see if epigenetics could be one of those

potential mediators in this risk to physical mental health comorbidity

Pathways um what it looks like so far is like this Association is probably a little

bit more complex than we expected so there might be very time specific element here and what’s also possible is

that something we we observe across a range of research studies is that it’s

not necessarily single methylation sites that might mediate this Association but

more like Global composite methylation with scores so those could be risk scores for inflammation or methylation

risk scores for cortisol or for epigenetic aging you know and that

really um mediate the link between Gene environmental risk and physical mental

health comorbidities perfect so you’re trying to connect all of the dots right your mental health your physical health

um through genetics through epigenetics and my listener should be hopefully familiar with those methylation risk

scores I’ve chatted about those before with Dr Michael Thompson so um yeah and is it then true to say Dr

Walton that you’ve created then a brain age or and have you created an epigenetic clock for the brain age and

um can you can you tell me a little bit more about that uh well we we used one we have created

it ourselves used one it’s not an epigenetic Brain Age although there is a

marker that we have uh studied in in our research and I can maybe explain that study in more detail but the drainage

measure we’re using is based on uh brain morphometry data so structural brain

data and it works similar to those epigenetic age clocks

um you know you talked about so as as you probably know there are like a whole range of different epigenetic age

markers you know there’s the hover clock in the uh Dunedin pays Etc and in in the

same way there are a range of different drainage clocks in a way there can be

sometimes based on structural measures such as you know the cortical thickness or how thick the

cortex is or your surface area or maybe volumetric measures that could be based

on based on the white meta amount in your brain so how different brain regions are connected or functional

connectivity so there are a whole range of different drainage measures in the same way how their whole range of

different epigenetic age measures and they’re all tag slightly different concepts so the

drainage measure we use is based on a combination of I think around 100

different markers of cortical thickness surface area and subcortic volume and in

a same way as epigenetic agents so biological age measure of of your brain

so it tells you kind of how old your brain is and then you can calculate the discrepancy to your chronological age

and you can see how that predicts certain Health outcomes so for example

just in the context of rain aging without every genetic age we we saw that

patients with schizophrenia for example show an advanced brain age compared to healthy controls

now what we were interested in is to see if that measure of brain age is

independent of all of those measures of epigenetic Aging you can you can obtain

and we looked at a population-based sample in in young adulthood so those

were individuals between the age of 17 to 24 and we had measures on epigenetic

Aging so we had the Harvard clock we had do you know age we had Dunedin pays and

we also had that quite interesting cortical as an epigenetic age measure of

cortical tissues um but obtained from blood samples so you can

use blood samples to get at a cortical epigenetic clock of brain Aging in a way

and then we correlated all of this with our structural measure of brain age and uh

the super interesting thing as we found is that they’re actually quite independent of each other oh really yeah

I would guess I would guess the opposite my hypothesis is that they would be no perfectly correlated but that you would

see a pretty strong correlation or Association yeah and and we didn’t and

we’re trying to make sense of that for a while and one of my students was leading

on that project she coined that term or she found it somewhere the Mosaic of Aging that you know it’s well possible

right that different that we have different ages right that some of our

organs just age at a different way than others so the the age we we get at when

we look at blood-based methylation markers is different to our brain age

and also different uh to our you know cortical epigenetic based clock and it’s

possible that these are largely independent maybe during early development but as we go through life

and as we adopt certain lifestyle factors and as we generally age as we get older

um maybe those different age markers become more and more interlinked to influence than you know motor Mobility

coming back to that intersection between both physical and mental poor health yeah yeah I’m curious to follow along

that data that’s definitely a surprising finding um to put it quite simply um I I’m curious about the Dunedin Pace

in particular in the correlation of brain age because I know in the creation of the Dunedin Pace algorithm they it

will let me let me back up and say people who have a faster than Indian Pace actually have less cortical

thickness they have less surface area of the brain and they have differences in that white matter hyperintensity based

region so yeah that’s that’s very interesting even if we’re getting those measurements that are included in that brain age with the structural data how

how we see those differences so um yeah I think it’s possible that it’s just that maybe those associations

emerge at a different developmental window and maybe they also work in combination so maybe those measures even

though they’re largely independent maybe during adolescence uh we we’ve seen in

other studies that in combination they predict uh you know functional outcomes

such as cognitive decline actually much better than if you just looked at an individual epigenetic age or Brain Age

measures so you know each one contributes a little bit to the overall prediction of the model again suggesting

you know there is probably a link between you know those more physiological epigenetic H markers and

the war brain based we need to look at everything together I think another Point um as well the

pre-print actually just came out like a couple weeks ago with raw gov Seagal’s paper he’s out of Yale where he has

created those systems aging clocks and yeah if you’ve seen those yeah so I’m

sure what he used for I don’t I I’m 90 sure there’s a brain clock I’ll have to

go back and check it may not be one that actually made the cut um but if he does that would be interesting because I bet what he did to

create the brain one is take a lot of that structural brain data so I I bet that one is probably going to be the one

out of any of them in terms of the epigenetic clocks that would have the best or highest correlation with your brain age so I’d be curious to see the

connection there really good point yeah yeah and um kind of moving on again you’re doing great with this this flow

of conversation Dr wall and I’m having a great time chatting with you you mentioned previously developmental

timing so um yeah tell me a little bit about that maybe let’s first Define developmental

timing and then why is that important when we’re looking at all of this stuff because you you mentioned the reason

that we’re seeing these differences might be due to developmental timing uh so do you have a bunch of timing I

suppose is is a bit I mean a bit of a complex issue but it fundamentally

refers to the fact uh or it combines different findings we we observe so

first of all that really weird findings that we’re more likely to identify longitudinal compared to cross-sectional

findings or associations and uh you know that there might be a certain developmental uh windows for

vulnerability for example so to maybe make this a little bit more concrete to

to describe what I mean with that um uh we did a study on ADHD so an

epigenomide association study on ADHD and we did it twice now and twice we

observed quite similar um findings um so the the study design was

um both cross-sectional and longitudinal so we had ADHD symptoms in Enchanted

measured in children around age seven to ten

and then we had DNA methylation data either obtained at the same time point

so cross-section B the same time Point as ADHD symptoms or longitudinal at

Birth already so about 10 years earlier now intuitively I suppose you would

think that when you look cross-sectionally you’re more likely to detect those associations just because

if two events are closely measured next to each other you know they’re likely to be connected so

um but we observe the opposite so we didn’t actually identify any cross-sectional associations and that

was a matter analysis so that was acquired people’s fighting across a whole range of different data sets

but instead we found longitudinal associations that DNA methylation at

Birth predicted later ADHD symptoms over like a 10-year time period

and that’s quite surprising right because you wouldn’t necessarily expect you know those those long-term

predictive abilities of epigenetics at Birth predicting symptoms and childhood

but this is something we we observe across a whole range of studies so we did a study on measuring the

ventricles in the brain so this is this area deep within your brain it’s like this cavity it’s it’s filled with fluid

and it has been linked to you know Alzheimer’s disease and has also been to schizophrenia so anywhere there’s this

region in in your brain and we try to predict that using DNA methylation data

and again just like with the ADHD study what we found is that when you weigh

your your methylation risk or by information obtained at Birth you get

better predictions even if the measure the brain measure you’re analyzing was obtained you know 10 or 20 years later

so that was that was quite uh surprising quite exciting so this is kind of what

we mean with developmental timing just like you know watching those plants you know you don’t observe it at the same

time but you know if you wait a month you know if you over underwater your plants yeah yeah no exactly right so you

you touch a little bit on why it’s important to look at these relationships between DNA methylation early life stress the brain and the mental health

so it’s all it all comes back to this preventative based approach right by being proactive by you know knowing if

you’re over watering or underwatering the plant when you’re doing it rather than you know waiting and seeing what

happens so the DNA methylation and looking and analyzing at these relationships give us I guess insight

into later health or you know future health State um is there anything else you want to

add there about why it’s so important to look at all of these connections

um well I suppose it’s it’s also important not just in relationship to to

Future Health outcomes but also to English to risk exposure

so you could think that uh risk exposure During certain developmental time

periods might have a larger impact on your epigenome or maybe on your on your

personal health then had you been exposed to that same risk or trauma at

different time points and you could have in a way a whole range of different

hypotheses that you might want to contrast so you know you might say actually the earlier you are exposed to

trauma the more severe the impact is or maybe they are critical windows or maybe

it’s it’s just a dose response effect so the more frequently you’re exposed to

adversity the larger the impact on your health so you can see those are

different developmental theories and they would lead to different predictions and different prevention and

intervention programs so what we what we did with collaborators in in Boston so this is

lab wolf Aaron Dunn and you know they’re leading there and we’re involved in that we developed this

um statistical framework it’s all method it’s called sligma structured life

course modeling approach where we can directly contrast those different developmental theories so does risk

exposure add specific developmental windows lead to increased

risk or larger impact on your DNA methylation compared to other time points and this is exactly what we find

we find that for example the study we just published on which we could also

replicate is that risk exposure doing um the years between three and five

years of age seem to impact DNA methylation later on more strongly so

than a risk exposure a different developmental periods and that that’s quite important right when it comes to

prevention and intervention programs you know can we really identify those critical Windows of course we’re still

long we move from actual interventions but if if those findings you know

replicate over and over again we we know better who to to Target and who to support best yeah yeah and then when you

just to be a little bit more specific there as well when you’re saying that you’re seeing these DNA methylation

changes later on in life when it’s between a certain developmental window what do you mean by DNA methylation

changes is that like with the eat with another ewall study or are you seeing things from like more of the biological

aging clock or different acceleration levels can you go a little bit more detail into that yeah sure so that was

generally an epigenetic um like an EOS framework where people get individual epigenetic markers so

different cpg sites so we didn’t look at epigenetic aging there and um perfect uh

yeah so that was DNA imagination why data obtained at age seven and then we checked again in age 15 different 10

points yeah that’s something that I really struggle with in explaining to people as well right when um I think

there are a couple studies out there looking at different you know Ace related events and you know adversity events and traumas when uh even there’s

a couple of study raised in a cohort of 13 year olds and then another one in 18 year olds with the danine din pace and

you know how those traumas affect the pace of aging and some other epigenetic based clocks but I think that’s really

hard because the older we become I it’s almost like we forget or we don’t know

if we underwent some type of trauma right so um that can be very difficult

for people to dive back into I I find at least when talking to people about reasons as to why maybe they have some

accelerated biological aging so I think yeah being able to have a predictor of that somehow that just looks at maybe

those certain cpg sites or how those are differentiated methylated and look at them in more of a single analysis rather

than these clocks could be very helpful I agree

and um okay Dr Watson so um you also State something I think pretty regularly as well in in your work

you say you know aging starts at Birth and that may seem I guess rather intuitive but

um what do you mean when you actually say that uh it’s it’s interesting that you say

this is a two-tooth I mean I think it’s intuitive right but yeah if you if you ask people you know if you just go down

the street or something and you ask people what’s aging or something or you know and they they often think of of old

people and you also see that in the research landscape right so yeah if you Google

aging and then you analyze the data sets that are being used in those aging studies

they often focus on people age you know 40 50 60 or older

and so it’s it’s it’s interesting right because you think like well hold on you

know let’s say you have a 30 year old you know is that person not aging or you know you want me back even more let’s

say you have a 10 year old child or something like is that personal aging well we would say like oh their child is

still developing you know it’s not aging right developing and you think like what is that is that the same or is that

different you know is it just a different name for the same biological

process or is there some kind of mirrored thing going on that development is the opposite of Aging

um so I was surprised to to see that aging is only almost exclusively studied

in the context of old age and um those research studies usually look

at outcomes such as cognitive decline or um you know grip strands

um yeah brain atrophy and and you can immediately see where the

challenge is lie because now let’s say we go back to that 10 year old child you know can you really measure cognitive

decline It’s Tricky can you measure brain atrophy you know that wouldn’t work grip strength also isn’t the right

measure um so even though when we when we think about it and we say like well yeah of

course aging starts at Birth the next question then is like how how do we even

study that you know how do we stop aging at Birth and I think that’s where those

um epigenetic age measures and those Brain Age measures come in really well I mean in the area of epigenetic Aging we

have some really decent measures that work really well at Birth so we have three opportunity gestational age clocks

we have you know pediatric epigenetic age measures you know buccal samples

in the area of brain aging it’s it’s a little there’s some measures out there but I think there could be a little bit

more diversity and maybe that’s coming with time I mean the area of epigenetics is really inspiring here you know with

the first second and third generation clock so I hope you know we we get there with brain aging too

and then I suppose the the the challenge is like uh you know can we really

measure Aging for birth onwards can we did somebody’s life course aging

trajectory and then can we identify measures that help people age more

healthily and can we identify risk factors but also we’re like really importantly protect the factors and

when when are those protective factors best placed um you know that’s coming back to those

developmental timing effects so let’s say uh engaging in in exercise you know

let’s say I didn’t exercise when I was a child and I didn’t start jogging until I was like 30 is that too late you know is

it still fine uh you know changing your diet or your sleep habits or something you know at what age is it best place to

make a good impact on your general aging trajectory across of course a complete lifespan no I mean

those are real questions those are practical questions that is what everyone wants to know the answer to I often struggle with that on on my

podcast you know the reason I created this in the first place is to bring light to a lot of the research that we’re doing but people you know this

research is so important I truthfully enjoy every single conversation I have with the people I I basically you know

interview and have these chats with but a lot of times people are like okay well you tell me exactly what I need to do

right what’s best for my epigenetic methylation what supplement can help what medication what can I be doing and

you know I think we’re getting there but I think it’s going to take time I I really do believe we’re undergoing like an epigenetic Revolution right now and

um will only start to understand this a lot better and have a lot of those correlated based studies that are always

going to sit at the framework of the research you’re doing so you know we are going to have to create better

predictors for people you could actually argue Dr Wall on that aging starts at the Inception right so you know um

that’s a whole different story like you were talking about those gestational age clocks but you could argue that it

starts at the Inception and then hey what are you supposed to do from inception up until you know 90 hundreds

past that what is the best of every single stage in your life from a lifestyle perspective or you know some

type of other Interventional perspective so I mean yeah so in the area of of drainage I think I suppose what was

speech but also like generally just describing cortical uh alterations and people with mental health problems so

something we found you know when it came to interventions is that um so we we studied people with anorexia

and looked at their um structural brain alterations we also looked at drainage working found similar

findings and uh what we found is that those um structural grain alterations are

actually um not permanent and they can modify again with therapy success so we we

looked at people you know who who just started um therapies so they were severely

animal nourished and just got into the hospital and I showed very high symptoms of

depression and anxiety and then we looked at people who were already undergoing recovery so they’re already

you know had some weight gain and their symptoms severity reduced that and what

we can see that was reflected in their brain structure so we could see those changes uh you know renormalizing again

in a way I mean we normalizing is a bit of a contentious term but you know we could see that those really extreme

alterations we observed when people are severely ill can change again with with

therapy for example and I thought that that finding really resonated with people so I got you know I got contacted

by people who thought like oh this is a fantastic finding because it it shows that you know you know if you engaged in

therapy or something and if you seek help you know you can make a difference and some of those changes if you

intervene quite early on or might not be as permanent as uh as some field so you

know there’s there’s really some hope there yeah I I think that’s extremely motivating and hopeful for you know

again we we talk often about from an epigenetic standpoint you know you’re more in the driver’s seat like you mentioned at the beginning 30 of kind of

the the brain functionality or however you’d like to put it is due to those genetics so there are ways that we can modify this through

um the exposome or again different environmental factors so um what about you know you just kind of

hinted on an application or a commercialization part of your testing is hey we can measure this we can

intervene with a therapy and see a positive outcome or change do you have any other ideas on on application moving

forward with some of your work and if not that’s totally okay I I just want to ask uh well I think you know in terms of

individual applications and you know personalized medicine we’re probably not

quite there yet uh you know to really make this work I think those

um those risk measures we’re using work some of them work really well on uh on a

group based level or population based level and I think the the main application is really to understand risk

Pathways and uh you know as I mentioned before you know when can

we intervene best um in in terms of personalized things um you know I’m looking forward to see how

the field is developing I know in cancer research for example you know uh you

know the future is much further in terms of pharmacoepigenetic treatments in terms

of um disease progression prediction for example in in the area of mental health

you’re unfortunately not quite there yet but maybe one day that would be cool yeah yeah and then you know what about

you personally what’s what’s next in terms of your investigations or or studies is it still kind of identifying

the connection with DNA methylation and epigenetics you know what are you looking at next

I know that yeah I know you’re busy um I think something I’m really

interested in is so we we just started the study um on uh G was on brain age to really

understand the genetic architecture of brain age and once we have those results

uh you know there’s a plethora or photo of studies you could do so for example you could see how the genetics of brain

age overlaps with the genetics of epigenetic age you know is there is it generally a shared genetic

um you know overlapping genetic architecture or they’re like individual components and then once once we did

that study we can also see um use more causative inference methods um like you know there’s this really

cool method called media and randomization where you look at genetic markers as proxies to answer quite

causal questions and that would allow you to assess for example is epigenetic

age is the cause of predictor of brain aging or maybe a downstream consequence or maybe

they’re not causally related at all and I think those would be fantastic for Life studies I’m really looking forward to those yeah I think so you’re

definitely gonna oh well I’ll I’ll keep out for I’ll keep an eye open for those studies but you’ll you’ll definitely

have to to keep me updated so um no this has been great Dr ball and I have a couple more questions left here

for you um I want to talk about um you know the methylation Imaging and

neurodevelopment the mine uh program that you’ve set up or this Consortium and yeah tell me a little bit about that

and what you all are doing what you’re trying to understand sure so the the modern Consortium was

set up like by a colleague of mine Professor Investments MC and myself here

and we co-leading it together to really study the associations between DNA

methylation and and the Brain in a developmental context so

um it was set up because there’s not a lot of data out there in that area so

we’re looking at at a day or to understand the association between DNA methylation and the Brain in early

developmental periods so some birth onwards and maybe even prenatally if you

like um but the the studies that have data available are often quite small so maybe

50 individuals 50 new babies or something and you know right and in epigenetic

research you you need really well-powered studies you know ideally thousands or ten thousands or even more

uh to identify those really robust associations uh so what we did is like

we we found this mine Consortium to collaborate with researchers and

research groups across the world uh who have data available like repeated measures data available of DNA

imagination so it’s different time points and of brain Imaging at different time points especially in the very early

developmental periods from birth onwards and we did that to to Really study the

complexity of those really early life associations in more detail to really assess uh you know the associations

between you know peripheral base of blood-based methylation and brain-based processes to uh you know understand

those early developmental um tricks because we know right that mental health conditions uh often have a quite early

neurodevelopmental component to it so we have unit disorders like autism or ADHD

and even disorders like schizophrenia you know there’s this idea that there’s a very strong new developmental

component to it and most people who develop mental health conditions develop them quite early on before they turn 18

so we really need to broaden out this early developmental time period and

collaborate importantly together you know so really pull data sets work

together and really identify those very robust associations with with more and better data ideally longitude and early

life yeah of course of course it’s really really a way to you know see what everyone else is doing

in the space and how we can all collaborate together so I’m looking forward to how that could Consortium

actually helps Advance the the field of neuroimaging epigenetics I’ll be um yeah like I said excited to follow along so

this has been great Dr ball and I I really can’t thank you enough uh for anyone else who wants to reach out or

find you um yeah how can they do that I know you’re active on Twitter I think I found you on Twitter initially alongside with

some of your research of course yeah so I’m on Twitter uh I think my username is Esther walton18 so you can find me there

or you can just look up my webpage at the University of bath in the UK where you find my email address and then you

know people can just contact me through email or great great I’ll make sure to include

those links in the the description and on my website and whatnot um doctor on my very very last question for everyone

that I ask is definitely has nothing to do with your research but if you could be any animal in the world what would

you be and why any animal in the world so many anyone

you want Dead or Alive like dinosaurs and stuff I don’t think anyone’s ever picked a

dinosaur but it’s not off the table yeah I don’t see why not hold on well I mean dinosaurs is tempting but let me think

about this for a moment um yes well no I’m not gonna pick dinosaurs

although it is tempting I got a um so there’s a a running joke in my in my

family so the kids make fun of me because well I I totally disagree with that statement but they say I don’t have

any other Hobbies but work and I would like to stay for the record that’s not true but to prove a point they did in in

best scientific manner a little survey at home to to to ask around and for some reason it turned into a survey about

favorite animals and I didn’t have one and so they assigned one to me and they

assigned the zebra as my favorite animal and I fully embrace

the idea of being as Deborah being all you know white and black stripy and the Savannah mining yeah one business and

hoping to escape the odd lion along the way so I I take zebras I like it no it

no one has said that before so we’ll we’ll go with the the zebra that’s amazing thank you so much for for

answering that question and I like the little backstory behind it as well so you can send this recording to the kids

and now you have it on record that you know you’re not always working you’re having fun talking about your research

too thank you so much well thank you so much Dr Walton thank you everyone else for

joining us here at everything epigenetics podcast remember you have control over your epigenetics so tune in next time to learn how thanks again bye