welcome to the everything epigenetics podcast where we discuss DNA regulation in the insights it can tell you about
your health I’m Hannah wet and I’m the founder of everything
epigenetics today I have an awesome guest for you his name is Dr Gabriel
Freeze first we hop right into it you all will get a nice introduction in hear from him about his personal journey into
his psychiatric research focusing on molecular biology and
epigenetics we then hop right into epigenetics and Psychiatry so what are the epigenetic mechanisms mediating the
interaction between genes environments and playing a key role in psychiatric disorders like bipolar disorder and
suicide risk specifically we also talk about aging in Psych psychiatric disorders so how
psychiatric disorders are really linked to accelerated aging and higher rates of age related diseases his research really
highlights that bipolar disordered patients especially those with suicide history have older epigenetic ages we
also get into lithium in aging so lithium may have H shown some anti-aging
effects such as tmar length elongation and bipolar patients and then we dive
into ongoing research um Dr freze is specifically looking at um markers um
and and investigating drugs that could Poss possibly prevent or reverse epigenetic aging we finish up talking
about future directions and where he’s taking um his his Interventional studies
um in the future with some invitro drug trials uh focusing on reversing those epigenetic biological age clocks we then
end by speaking about his challenges and future work he’s excited to continue on
so very briefly about my guest today Dr freeze is an assistant professor in the
a department of psychiatric and Behavioral Sciences and a translational researcher in the field of biological
Psychiatry again he focuses on the epigenetic bases of mood disorders
particularly bipolar disorder suicide and mechanisms of stress all right um he
also collaborates with basic and clinical investigators to search for the genetic and epigenetic underpinning of
severe mental ill illnesses now he’s received several grants he’s a principal
investigator and he’s currently funded by the National Institute of Mental Health um and um is running the UT
Health Department of Psychiatry and Behavioral Sciences and now for my guest
Dr Gabriel freze welcome to the everything epigenetics podcast Dr freeze I’m
excited to have you today thank you I’m excited as well thanks for the invite yeah and we’ll
start off with just some general know knowled about your background you know I’m always so curious to hear how people
end up in their particular field whether they took a very traditional path or maybe not so traditional so your history
in particular is extremely interesting to me um because of the subject we’re
we’re going to be talking about today so can you just give us a little bit of background on your journey and and how
you ended up you know doing what you’re you’re currently studying and looking at
sure well it’s supposed to be a simple question but sometimes it is I know how
to answer that but I I’ve always known that I wanted to do scientific research and medical um research in general um
and when I started my undergrad um my college experience I started to try out
a couple of topics you know I immediately entered into a research lab but then you know fell in love with uh
biological Psychiatry as we call like this idea that we can contribute to the
psychiatric research um by providing some biological insight and some molecular underpinings to these
disorders which normally are not seen or not necessarily seen as um medical
diseases in that sense right it’s easy for someone to understand cardiovascular disease or something that is related to
molecules and all that so when it comes to psychiatric disorders there sometimes are some um you know limitations and
some restrictions as to okay that makes not be the case but in fact I truly believe that it is and we’ve been doing
this work for many years now so I I did my masters and my PhD specifically in
Biochemistry so I really wanted to get into the the molecular uh level of
everything with a focus on psychiatric disorders came to the US so I’m
originally from Brazil so I came to the US to do a post do uh eight years ago um
here in Houston and you know the the topics come out of each other right so we
started working with epigenetics in general that has led us to study epigenetic aging and aging in general
when one thing keeps leading into one another but I still am very passionate about the field and excited with what it
can lead to and the contributions that we can make in the future yeah for sure
and I think it’s safe to say you’re an expert in the epigenetic basis of of
mood disorders and Psychiatry you perfectly out what we’re going to be talking about
today you know so so that kind of leads me ex directly into my next point which is is great I want to really dig into
this though because you have all of these really great papers um I think it’s better if we start big picture like
you mentioned and just talk about epigenetics as a subject so why is it
important to study this more in particular the psychiatry in relationship to
epigenetics yeah so epigenetics is a really interesting um route to study Psychiatry
for a couple of reasons so just um for the sake of introduction right so we’re we’re talking about mechanisms that can
affect gene expression in response not only to our genotype or to our genetic
background but also to the environment and that fits perfectly with what we believe um is implicated in mental
health or psychiatric diseases right so they are all known to be multifactorial diseases meaning that one needs a risk
genotype to interact with environmental triggers or you know things that happen throughout life um and and so it just it
makes sense to think that epigenetic mechanisms such as DNA methylation noncing rnas or histon modifications are
mediating this interaction between genes and environment um so we’ve known for many years that psychiatric disorders
are heritable meaning that um they are clustered in families um
offspring of individuals with diagnosis tend to have a high risk of developing
this disord so there’s this genetic component that right now cannot be fully
explained by just looking at the DNA sequence and and that’s where where you know epigenetics and our work comes into
play is to try to to complete that whole picture right to paint the whole picture
um in addition to ongoing genetics studies first say that are actually looking at varians and mutations and
things like that MH sure yeah I just think it’s so interesting I think if I were to go back through school I I
definitely took a very traditional route of the general biology degree path um I
would go back and do more of like the bioinformatics or definitely psychology I remember I took like Psychology 101
and it was just fascinating I’ve always been been interested in that so again that’s why I was so excited to to have
you so now we’ll we’ll go a little deeper but talk um I guess more more
General in terms of epigenetics and then Aging in Psychiatry right so we get to this idea of epigenetics people usually
tie it into aging so you know how can we look at these factors and maybe mitigate or reverse some of them as well so you
know when you’re looking at psychiatric disorders and epigenetic aging from a broad perspective what are you really
finding and and you know we we can go through some of your papers later as well um but you can even go a little bit
into this spefic specifics too yeah so the the big picture here or
the the basis of all of these aging epigenetics and Psychiatry um studies
that we do are based on the fact that most of these disorders are associated with a premature
mortality and or a higher incidence of um age related diseases and you know
cardiovascular disease diabetes dementia um or a faster clinical uh
cognitive decline you know over time so there were these clinical suggestions now that an
acceleration of the aging process may be taking place uh in some patients with
psychiatric disorders and in a sort of independent line of research there have
been many studies proposing that the process of Aging includes epigenetic
mechanisms as you know and I’m sure you’ve talking about this over and over with different guests here so this is
when these things came into play right we thought a couple of years ago and uh we were certainly not the first uh to do
this we thought well maybe epigenetic mechanisms may be underlying these um
you know as the these findings that people were having that there’s an accelerated
of the Aging processing these diseases one sort of lwh hanging through to study
this is using DNA mation levels to estimate these so-called epigenetic clocks or you know markers of pace of
aging and these things that um you guys are very well familiar with and so by we
started doing that with a lot of the sampol that we have in in our lab we’re particularly interested in bipolar
disorder and suicide those have been the main focus even though we’ve worked you
know in collaboration with other groups that um have included samples from other diseases and in general we do see a
pattern that’s similar to what we would expect in a way we see higher or older
epigenetic ages or age estimates in patients with these diagnosis or
individuals with these diagnosis compared to non psychiatric controls and um well a couple things we that’s not
seen in every single patient so that’s an important thing to to establish now
it’s not a deterministic Association and we seen we see some clinical
associations that may be of interest so for example in the context of bipolar disorder in general you see that the
diagnosis is associated with the higher acceleration of the epigenetic aging process but within individuals those
that have a um history of a previous suicide attempt may have an even higher
um acceleration of the epigenetic agation process so we see these nuances
and and differences even Within the large diagnostic clusters that we talk about gotcha yeah and why do you think
that is that’s is that what your you know your main questions are now is trying to dive dive into that a little bit further because I I have here as
we’re we’re kind of going through you know our agenda you look at all of these different um disorders right you
mentioned mostly the the bipolar and and suicidal but I have you know schizophrenia different anxiety
disorders you know substance use disorder as well so it’s it’s you’re really really trying to find those
different subgroups and all of these factors which may be affecting those clocks and what that means yeah I mean
that’s the that’s the the question now now is to try to find the drivers of
these uh findings now that we’re just seeing I think that to some extent we’re just finding the you know final outcome
if you will but we’re not getting a sense of the process and what’s necessarily leading up to those alterations that we see most of our
studies so far have been in cross-sectional studies so these things need to be seen with a grain of salt
we’re looking at that one time point in the life of the patient um even though we we discuss it as an
acceleration process really when it comes down to it since we’re not following up these patients um with
these markers we can’t really argue that there’s an acceleration what we see is that something that happened up until
that point has led them to have older epigenetic ages and we of course
extrapolate and generalize those findings but I always like to think that you know we need to be a little bit cautious of that um so in even in the
limited context of a cross-sectional study um you can make inferences or at
least look for correlations and associations with clinical factors and other things that can maybe generate
hypothesis for future studies um and so we see for example that within
individuals with bipolar disorder those that have a older epigenetic age
compared to their chronological age they tend to have um worse cognitive
dysfunction if you will now so we see this logical but yet for the first time
actually empirically shown association between the aging process and its acceleration with higher degree of
cognitive dysfunction or C being paramid however you you like to call that um
like I said we see association with history of suicide attempt which is an
interesting finding as well to think that this one possibly very traumatizing
event in the life of a person can have an impact in you know your biological
clock um in in fact there’s a lot of evidence suggesting that um survivors of
a previous suicide attempt also die earlier in a way and that cannot be fully explained by Suicide itself so you
know that it makes sense that maybe that aging process accelerates after that um
I think that also overlaps a lot with the PTSD um literature that I’m not you
know a part of but I follow in the sense that these um these individuals also
seem to have accelerated epigenetic aging so there’s a lot of discussion about the importance of these traumatic
stressful events um no leading up to those so yeah this is you know there’s a
lot to explore there in terms of the causes but since we’re seeing these associations with potential consequences
now which serves as a basis for most of these studies I think that’s interesting I think that’s worth pursuing the
mechanisms that are leading up to those alterations um so that we can start to Target them in fact right so of course
it’s only hypothesis at this point but what if we can somehow prove that it’s
through these accelerated epigenetic aging processes that you know a lot of
these age related consequences end up taking place in patients what if we then
can use some of the findings that we have to propose ways to Target the Aging
prevent those consequences and ultimately increase lifespan and promote healthy Aging in patients I mean this is
the the significance at least that we try to focus on when doing these types of
studies exactly seems like everyone I’m interviewing and all of my guests who
are phenomenal they all have that same goal eventually right they may be studying different subjects or different
um this diseases or disorders but yeah it all comes back to hey if we can identify this take more of a preventable
approach preventative approach then we can get a better outcome so I just think that’s that’s really the beauty in in
looking at these markers and I know you mentioned you’re basically getting the
the data from one time point are you able to follow up with a lot of those um people from the study are you able to
get any longitudinal analysis is that of of any interest it is definitely of interest um our group here in Houston we
have some patients that come it really depends on the study that they’re involed uh for um but we haven’t been
able to run these analysis yet um so in fact this is one of the things that I’m
doing right now is I’m trying to um you know reactivate this discussion our department to start
recruiting those people again um because of course they all volunteers it’s it’s
it’s a hard process right any longitudinal study is tricky um or even
find collaborations maybe a listener uh of the podcast who has similar samples
that you know would be interested in in letting us hype with the process of measuring some of these markers that
would be wonderful because I think that’s a a very logical next step in our research and something that we want to
pursue I mean like I said we are extrapolating a lot of things from these cross-sectional findings and that’s
great Al be limited but the next step is exactly to see what comes first right so
we have some unpublished very preliminary evidence that maybe some of these uh accelerated epigenetic aging
markers um they are associated for example with metabolic dysfunction or inflammation so you know not going to
talk much about it but we just see these things and now the question is what comes first right is it um is is it the
case that these diseases these disorders are leading to some of these somatic
medical changes that ultimately lead to the accelerated aging process also
mediated by the environment and all that which makes a lot of sense but is it the
opposite right is it maybe an epigenetic aging process that’s
already accelerated that may be to some extent is already being dictated by the genetic profile of these individuals
then then contributes to a lot of these metabolic inflammatory and you know many
other alterations that will end up activating and and leading up to the higher risk for age related diseases
dementia etc etc I think that this is an interesting discussion that will probably only be explained when we
really look at large groups of people over time right
longitudinally yeah it’s an interesting interesting way to look at it but as more of the data and research comes out
we’ll be able to answer some of those questions which will be great yeah um keep digging a little bit deeper here
and um you know this comes up I would say quite frequently but I really want your take on this as well you know there
are a lot of epigenetic age clocks out there and and they’re all great I think there there’s ways you can use each of
them and they each have their own application um in your most recent work however you note that one of the
strongest associations with mental illnesses have actually been in those newer second generation based clocks um
and those are going to be the biological age ones you know we we’ve defined that in previous shows before rather than those chronological ones um so these
second generation ones you know the pheno Age based on clinical measures of phenotypic age and then we have the Grim
Age based on DNA methylation surate plasma proteins linked to different outcomes so can you just speculate on
that why do you why do you think that is yeah I think it has to do with their the
way by which they were developed which Echo what you just said right um the first generation clars as we call them
Horvath theum they they had the sole purpose of predicting chronological age
or you know the time since you were born um and again how great it it is to have
a marker like that for many different reasons for for insects even um a lot of different application
but we know that chronological age is a very poor predictor of age related
conditions um so just by having something that predicts your chronological age when you look at the
clinical significance of that is probably just as limited as the chronological ages a variable itself
right I think I mean again we can extrapolate we can compare that to the chronological age and see if it’s older or younger and make estimations out of
that but that was not the point of those original know clocks um now like you
said pheno age Grim age these second generation clocks they were the idea was
exactly the next step was to not focus on time since birth rather on actual
biological markers of Aging or things that were related to the process of Aging one of them being the time until
death right time to death um which makes a lot of sense for me Ian this is the ultimate um consequence of the process
of Aging which is the grimage itself so it’s it’s really not a surprise for me
when we you know we published a lot with the first generation clocks when we started uh calculating the second
generation clocks that’s when most of the very interesting findings started to
to come to light um because of that I think that we’re finally capturing
meaningful biological aging um processes um and of course um we nowadays have
even more sophisticated ways to estimate that which is you know these third generation quarks
that you wereare well aware of yeah I think we’ll start to see the research
shift that way I at least hope right it’s it’s nice if you get first gen second gen you can you know maybe all of
them in there so you you may be able to see correlations and Trends but I I really hope to start to see that shift more of those second generation clocks
because sometimes I I really don’t think that people are aware of those different Generations right they hear biological
age and get so excited so I just always like to to point that out and and note that that difference but yeah you’re
exactly right what about the denin pace you I I heard you throw it in there uh
at the beginning so have have you looked at the implications of psychiatric disorders and and all of your work with
the pace of Aging metric yeah so I’m I’m going to disappoint with my answer here because we we started looking into that
so we used a lot of the data sets that we we’ve worked um to up to now and
generated need Cas from them I mean thankfully the codes and algorithm are open for researchers so cud us to you
know the group of ser offord and all that for for making this available um and we’re starting some analysis on that
I can see that they’re very exciting um but there’s we haven’t published
anything it’s really what’s what we’re doing right now is trying to follow up with these new markers which I’m very
excited about I mean I think that being able to capture pace of
Aging uh for one thing is is a huge advantage in in the case of our research
questions over the existing clocks that are out there um not to say that the
clocks are limited in a way but they’re limited for what we’re currently using them for in our research right so we
make a lot of extrapolations about the acceleration of the aging and we make a
lot of assumptions that really are about pace of Aging if you think about that um
and so that’s why like I’m excited to actually have a marker that nowadays can directly assess that um yeah so it it’s
it’s ongoing um I hope to have some some really cool things coming out soon well
good I I’m I like how you laid the groundwork you said all right you all will be disappointed but here it is well
no you’re you’re currently looking at it right and that’s kind of where my mind went when you said you know we’re
looking at people who had uh a suicide attempt and they’re aging afterwards right like my mind went to oh wow that’s
that’s super interesting I wonder how their Denon Pace would play out after that right so even furthermore the
longitudinal data of the Denon Pace to right before and after so it’s just it’s all super interesting and I think we’ll
unlock some some different levels you you start to dig dig more into that yeah yeah and and the suicide is a you know
obviously super sad event but it’s a fascinating topic of research in that sense because you have different
phenotypes as well so all of this I just shared with you that’s published that’s related to suicide attempt but we’re
doing a couple of you know studies nowadays to see what happens during the suicide radiation for example um and and
that’s the type of of markers in Jen P that would be really interesting to
check because for example we’re looking at Patients during an acute sociation event and after recovery from that
episode and so how cool would it be to see whether the pace of Aging changes as you recover from these um very toxic
brain events yeah yeah no that would be be great and I can just tell how passionate
you are about everything you you talk about so I have to ask what’s your favorite um you know subgroup to study
or or where does your passion really lie do you have a favorite um well I probably should say bipolar
disorder um just because of the you know the track record of it I mean I’ve I’ve
been studying it since my Master’s Degree back in the day uh when I was in Brazil and this has led me to come here
to continue working with bipolar disorder it remains um the main topic of
our studies even though we try to expand a little bit and see you know other events and other phenotypes in the
context of bipolar so that’s when we talk about suicide attempt and ideation within patients with bipolar disorder
and things like that um yeah it’s just a topic that’s of really great interest to
me um I think that there’s a lot of opportunities to help patients um yeah
and I hope to be able to continue in the fut yeah no that’s great I I had to ask
because it it’s just radiating radiating through you so we we’re appreciate we appreciate all this this great great
work you’re doing um we’re going to keep keep digging into this further so one
one other important point you mentioned um in your work is that the feature of features of this accelerated aging are
not found in in all patients but there’s um with substantial heterogeneity so
even within the same clinical diagnosis and you can explain what that all means um but I think this is profound and I’d
like to understand this a little bit more so can you discuss why you see this and maybe what it means just a little
bit a review for our listeners yeah well I think well it’s not surprising that
you know whenever we measure any sort of biomic or biological ceration in in these
individuals um you never see the same pattern in all of them
let’s say compared to people that do not have the disorder I mean the same way that you if you compare to people in
front of you that have uh diagnosis of bipolar disorder let’s say they’re going to be very from one another clinically
speaking right they probably don’t have the same combination of symptoms and
that that comes you know it comes with that discussion of how heterog heterogeneous the diagnosis is it when
you go to theology um so even if as a group the
diagnosis is associated with a higher you know process of Aging uh like we’re
saying if you look at the individual data you have patients that of course have very high but you do have patients
that have very similar uh epigenetic ages compared to controls it’s really an effect of the
you know the group and when you apply a statistical method there you see the difference and that’s when I that’s what
I mean when I when I say that it it it’s not a process that takes place in every
single patient and I think that’s important because it it shows you that um first of all anti-aging
um uh interventions for example may not be useful for all patients right we may
be focusing on one very particular subgroup uh within the
diagnosis um and on the contrary there may be potentially more severe
presentations where you would already see accelerated aging patterns in let’s say very young people um so it it’s
interesting to see this heterogen because you also it opens up for a lot of other sort of clinical implications
um if you think about treatment for example it’s very common that even gold
standard mood stabilizers an psychotics anti-press anti-depressants they do not
all patients respond to those drugs the same way in fact I mean it’s it’s a very well-known fact that there’s you know
for example lithium only onethird of patients will respond you know accident
in an excellent way to to the drug so you have this variability that may be explained and may be captured by some of
these epigenetic markers that we’re studying for example aging now like lithium has antiaging properties we’ve
seen this in vitro um but it may not be beneficial for patients that do not have
an accelerated inun process in that sense and maybe that overlaps with lithium response if you I mean I’m just
really coming up with hypothesis here that we have not tested but uh it’s one of the opportunities that finding these
subgroups of patients may offer sure sure and we um no that makes makes a lot
of sense so I’m I’m it’ll be interesting to see the reasoning be behind that as well um I’m going to run with the
lithium that you just brought up and and we’ll we’ll switch to that subject so this is going to sound so silly I’m
going to say it anyways as I was looking through your research you know putting the agenda together and everything I was
like oh this is just going to be such a great conversation and I spend most of my time speaking with
healthc care providers about aging and different interventions and you know the the studies of what’s been published and
I’m like I need to go back to that lithium study I always talk about with my providers and um see what Dr freeze
may think about it and then I was like this is his work I I just didn’t put two
and two together and I should have known um so it’s a little bit of an embarrassing backstory but here we are
and um we’re going to chat about it so yes you have that mini review um
and it’s called the anti-aging effects of lithium and bipolar disorder so um you know I think we like you said we’ve
always known in vitro that it’ll have a effect or or you know something with aging so can you um describe what you
found in this study I think most people who at least my healthcare providers who are listening are going to be interested
in this part yeah there so there’s a vast literature on lithium showing how
neuroprotective it can be or you know how about the effects of like lithium on
inducing um anti-inflammatory processes or protecting increasing self resilience
against you know stressors and things like that oxidative stress you name it it’s it’s a well-known
neuroprotective drug at least you know preclinically speaking that’s very uh clear
um what people have found and we later replicate in our lab is that lithium
also interferes maybe through all of those Pathways in terms of um oxidative stress and inflammation it interferes
with the Tome length which is as you know very classic uh marker of Aging um
and there’s in fact you know there are a lot of studies even going deeper into the mechanisms by which it can take
place I mean through gsk3 beta inhibition you can um activate a bunch
of Pathways that ultimately interfere with the tase enzyme that can lead to the extension of that portion of the
chromosome um we found a couple of years ago and we published this here in Houston that if you treat cells from in
that case it was lymphoblastoid cell line so it’s one cell line that was reprogrammed from lymphocytes from
individuals with bipolar and controls we found that in the cells from the
patients lithium was indeed able to expand and elongate the til length
showing you know that it providing some evidence of its anti-aging properties
however we did not see a similar effect in the cells from the healthy
controls um so in a way it shows that yes lithum can have an
anti-aging effect but it may not have the same protective effect across all
cell types right so it’s still not a good idea to put lithium in our test
water or something like that if you will um it’s still something that can come
with a lot of adverse side effects it may be protecting in you know in patients and in in certain situations um
but it does seem very convincing again this was a replication of findings from many other groups showing that lithium
can have that effect in addition to its uh neuroprotective effects yeah you that’s that’s great to
hear I wanted to to grab on to to that that that snippet that you mentioned so so thank you for that um what about the
future development of of your work you know what is all this this great research that you’re doing tell us about
novel treatment strategies for these these diseases so maybe you know they could be more specific based on the sub
group or where do you think that will lead to yeah yeah that’s what we’re tating into right now in ourwork is you
first of all really understand what’s driving these aging processes
and by doing that identify ways to prevent that or even reverse if you will
if that’s at All Pro possible and finding um trying to find the you know
what can we do what we can do to prevent that so we’re we have a study now right
now testing or screening a bunch of drugs that for a couple of reasons we
believe may have anti- epigenetic aging effects um so we’re working off of the
hypothesis that as you know one of the main um one of one of the strongest
findings in the anti- literature is Cal restriction right so it’s the thing that we don’t want to do but if you stop
eating uh reduce significantly with without inducing malnourishment you I
mean seem to um delay the process of Aging so in fact there are some drugs
nowadays that can mimic the molecular mechanisms of that calie restriction without actually forcing you to make
that caliber restriction so we’re testing them in the lab and you know both in cells from healthy controls in
from individuals with bipolar disorder to see whether they can in fact prevent or modify that epigenetic aging process
we comparing that to for example lithium which is like I just said a drug with um
alleged um anti-aging properties and more than that we’re trying to see whether we can expand these results into
the ran um the clinical like real world um setting right so maybe patients that
respond to lithium are more likely to benefit from anti-aging drugs or maybe
uh individuals that have a high accelerated aging process at based lar
are the ones that are more likely to benefit from a specific type of drug um so on and so forth so this is where it
comes into play and I think that that um relates a lot to this idea of phac
weapon genetics in a way that um maybe based on these Baseline epigenetic
markers be it epigenetic aging marker or
specific genes that are mated or groups of genes that are mulated demolation we
can predict whether someone can respond well to a particular treatment or
not yeah and oh that’s just that’s fascinating um and and is that um are
those studies ongoing right now the ones that you mentioned where you’re looking at different that mimic caloric restriction yeah exactly we’ve gotten
funding from The milkin Institute to do some of those experiments and I think that the ultimate goal is to find drugs
that can be either fully you know newly developed or even repurposed like drugs
that we already know are safe for humans I think those would be the ideal ones and that’s those are ones that we’re uh
testing right now um and you know based on our results in the laboratory setting
potentially propose some clinical trials you know with maybe starting with um healthy volunteers uh I mean non-
psychiatric volunteers and then maybe even patients see if that can have a positive effect as an add-on or even as
a standard long medication and Dr fze I I want to touch in on that point there
so I I know there’s this need in these studies to have more true Interventional
studies so you know with everything we were just talking about are those going to be purely ventional trials what are
some things you’re starting to look for in your lab yeah so far um they are
Interventional and the since that we’re testing their direct effect on these aging markers in an invital setting um
so we’re not testing them in patients um but that’s ultimately the goal right so
what we’re doing right now is we’re screening several different drugs that have this calorie restriction mechanism
um link to them and then we hope to find those that have the the most promising
results in the epigenetic Aging realm and then maybe propose them as clinical
trial later on for both individuals with a particular diagnosis or even for the
general population yeah I I think that’s great of course we we know the the need for that in in in this epigenetic world
I should say most people are excited about that but they don’t realize there’s a lot of work that goes into it beforehand too
to actually get to that point so with those Interventional trials or even
maybe some things that you’ve done previously in your work what are some of the challenges in in your field that you
think should should be addressed or you know as as a researcher what do you run into that’s that may be a little bit
frustrating that’s a good question I think that we we La replication of a lot
of the findings that we end up having um so for example my own group we’ve published quite a few
papers trying to convince people of why epigenetic aging is important in the context of bipolar disorder suicide and
all that but I want to say that most of the studies have all been performed with the same data set pretty much right or
the same group of people here in the Houston area so I really want more groups to start testing them in their
own cohorts and I think we need that for the field in general we need replication
we need large groups of people being tested for the same thing so we can see what are the findings that survived this
not this this replication uh trial um I think that in the realm of
epigenetic Aging Psychiatry we definitely need more longitudinal samples to be run um we are making a lot
of inferences and assumption about acceleration but at the same time we’re studying crosssectional data so it’s
really not the ideal data set um to test this so definitely longitudinal samples
um by doing that I hope that we can start exploring in more details this
heterogenity of patients like we talked before it doesn’t look like every single
patient has an accelerated epigenetic aging process and I think that one of
the perspectives of the field is trying to understand why that is what makes one individual more likely or at higher risk
for premature aging and While others you know don’t show the
same pattern maybe those that do have accelerated aging processes will benefit
more from certain types of treatments like the ones that we were talking about or any type of intervention that can
have an anti- ugene effect um another maybe bottleneck here that
we’re trying to explore is trying to understand what drives these processes
right what what are the underlying molecular mechanisms that actually lead
to accelerated aging uh processes in these patients and maybe by knowing
those we can Target them and ultimately prevent and or reverse epigenetic aging
in in individuals with bipolar disorder with previous history of suicide attempt and so on and so forth and ultimately
use that to to proposed novel treatments and again tying it back to what we just
discussed about this new potential anti-aging drugs that can benefit patients in in a lot of ways and
I think that’s the ultimate goal of our research is to help patients help their families help clinicians and hopefully
reduce morbidity premature mortality the incidence of AGM related
diseases so on and so forth of course I think those are all very valid points
and as I have more people on the podcast I’m getting more of a consensus of those
points as well so um it’ll be interesting to see how how we we attack
that um but again with time I think all of those will come right we’re going to get larger training uh data sets we’re
going to get larger validation data sets we’re going to get more information as to causation rather than correlation
right and then you know again setting up these uh you know I I don’t I don’t know
the right word I’m looking for but these fundamental I should say choric restriction trials things like that and
being able to use that as a proof of concept study and then follow up with that cohort you know 10 years later down
the line 20 years later it really sets the framework and the groundwork for um
more things like that so um all heading in in the right direction but I think it’s very important that people are
aware that um it’s it’s not easy right there there are there are some Road bumps and and things that we have to
overcome um so we’re we’re getting really close here one of the last questions Dr freeze what’s next for you
uh what are you excited about I know you have a lot going on some of those Interventional trials but is there like one thing that really sticks
out um I think I kind of mentioned some of those when I was talking about the
perspectives of the field I basically was listing the things that I expect to do in in our group um so again we’re
following up on those um molecules in an inv V sort of setting but we work with a
lot of clinicians here in the department that you know can help us with the next step which is to actually do small
clinical trials with with individuals with bipolar disorder um I’m very
excited with new collaborations with these larger samples that we can then test the same sort of questions that we
we have answers for in our own Houston sample and see how how those things behave in other cohorts looking for
longitudinal samp exles um and yeah just collaborating with the fud and and
contributing to this very exciting possibility which is to maybe Target
aging and by doing so improve the lives of patients so I guess that’s that’s
what’s hopefully next for our group and for the feud as a whole good good well I’m I’m I’m glad to hear that and
excited to to follow you along in this journey um and and look at all of the the work you and your your team are are
doing and continue to do so uh one of the the very last questions this is more
of a curveball I always say it’s very random and it wasn’t on the agenda but
uh Dr freeze if you could be any animal in the world what would you be and
why wow okay uh unexpected
question um I think it would be a dog maybe a lazy a lazy an
but I’m a I’m a big dog person and I I cannot think of a better life than to be
a dog in a family in fact my family just got a puppy so we’re all about that
right now um very cute what kind of dog or what’s its name it’s so her name is
Abby she’s an Old English sheep dog um she’s adorable and she she lives the
best life that one could have right so she sleeps she eats she gets treats she plays why would I
not want that life so I agree I’m a big dog person too um I I have a dog she’s a
Bernice mountain dog and her name’s Eevee and I do look at her sometimes and
just say like I just wish I could be her today like eat get like you know belly rubs
and everything can we switch lives for a day and you stay here I’ll stay here and you
go write the grants for me at work yes there you go well you know we’ve come to
the end of this amazing podcast interview and for anyone listening who wants to connect uh with you Dr freeze
where can they find you yeah um so I’m on Twitter at freeze
Gabriel um and you can also find me in the UT Health University of Texas Health
Science Center in Houston Department of Psych website there you can find links to our to our projects and to to our
publication and you can always send me an email with questions or requesting papers I’m always happy to to talk to
people um not just researchers but you know patients family members it would be
a pleasure to share some of our work with you definitely and I I’ll put everything in the show notes that way
people can can get in contact if they’re they’re wanting to so thank you so much everyone for listening and joining us at
the everything epigenetics podcast remember you have control over your epigenetics so tune in next time to
learn more thanks a lot Dr freeze I appreciate your time thank you
