February 26, 2025 • 43 mins
Unlock the secrets of a longer, healthier life with guest Stetson Thacker, PhD, as he sits down with Host Holly Thacker, MD to discuss the fascinating interplay of genetics, exercise and longevity. Listen to discover how physical activity might be the key to adding years to your life.
Explore the frontier of genetic testing and anti-aging supplements with insights from both Dr. Thackers. From foundational health habits to the exciting possibilities of genetic factors in longevity, this episode offers practical wisdom and cutting-edge science for those seeking to enhance their well-being - and lifespan.
Listen to Stetson Thacker, PhD's new podcast Views From Cleve-Mandu and follow him on Substack at stetson.substack.com.
Welcome to the Fit, Healthy and Happy Podcast hosted by Josh and Kyle from Colossus...
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:01):
On this episode of Speaking of Women's Health we
have a recurring guest.
I'm your host, dr Holly Thacker, the Executive Director of
Speaking of Women's Health, andI am back in the Sunflower House
and joining me on this episodeis my son, dr Stetson Thacker.
No relation, of course.
(00:22):
He is my oldest son.
I talk about him all the time.
Stetson Thacker no relation, ofcourse he is my oldest son.
I talk about him all the time.
He was a guest on season oneand it was one of our most
listened to podcasts in the over100 plus that we've done.
So he joined us back in seasonone to talk about genetic
testing for cancer risk and howour genetics can help with
(00:43):
weight loss and how to continueyour weight loss resolutions
with a few simple tips.
So on this podcast we're goingto delve into anti-aging in
terms of genetics, the biology,the history that we know of the
hacks and maybe some potentialpitfalls and manipulations to
(01:05):
watch out for, since it's reallyquite a hot topic.
So a little bit about DrStetson Thacker.
He completed his PhD in genomicmedicine at Case Western
Reserve University and theCleveland Clinic Lerner College
of Medicine under the tutelageof the late great Dr Dr Karis
(01:25):
Eng, who unfortunately departedthis earth.
She was really quite ascientist and trailblazer.
So Dr Stetson studied theimpact of genetic variation on
protein structure and function,as well as clinical traits in a
cancer syndrome called P10hamartoma tumor syndrome, and I
(01:50):
certainly have the privilege ofseeing many P10 patients in my
practice courtesy of oralreferrals from Dr Eng and her
group.
Now Stetson has authored severalcolumns on speaking of women's
health.
He's actually a prolific writer.
He published a book on poetrywhen he was in high school and
(02:12):
also was a first authorpublication which is highly
cited in fertility and sterility, from research he did when he
was a high school student.
Today he is the father of twoadorable girls, my
granddaughters, who just are soexcited to see me.
By the way, when I go to theirhouse they squeal, and when
(02:33):
they're getting into my car myson wonders why do they like
your car seat?
I'm like no, they just likecoming with Mimi.
Anyway, stetson's very busy.
He works as an associateclinical variant curator for
Natara, where he interprets andclassifies genetic variants
detected by the burgeoning fieldof molecular diagnostics.
(02:55):
And Natara is a global leaderin cell-free DNA testing and
it's dedicated to oncology,women's health and organ health
all things near and dear to ourhearts.
In his free time he writes onvarious subjects, which we'll
talk about at the end of thepodcast, which include cancer,
genomics, and his substack isstetsonsubstackcom, and he just
(03:22):
started his podcast.
I guess he's kind of like hismother in that regard.
So, stetson, welcome.
Thanks for joining us againwith your busy schedule.
Speaker 2 (03:32):
Thanks for having me.
Speaker 1 (03:34):
So I thought it would be really interesting to talk
about anti-aging and what aremaybe some of the best
anti-aging strategies that ourlisteners might want to be aware
of or think about doing.
Speaker 2 (03:48):
Yeah, there's a lot of hype in the space.
The longevity space is the termof art we hear now a lot.
I think the best way to thinkabout it is from two different
perspectives.
There's the individualperspective how can I do things
to help myself live a morehealthy and longer life, which
is how most people are thinkingabout it.
(04:09):
And then there's, of course,the population level, the public
health level perspective, andwhat can we do for the the
health of the population, tohelp people have longer life
expectancies, lower mortalityrates and so on.
And so from the individualperspective, there isn't like a
ton of things that we know forsure will definitively extend
(04:31):
your life.
I mean, if we did, they'd beplastered everywhere, everybody
would be doing it all the time.
We kind of know these sort ofgeneralized health
recommendations that we havethat are you know, eat healthy,
exercise, sleep enough, thingslike this.
Speaker 1 (04:51):
Things that we focus on on so many of our podcasts,
by the way.
Speaker 2 (04:54):
Right, and it's not to say I mean, those are
important things that we shouldfocus on, living healthy lives.
We know what a healthylifestyle constitutes and we
should focus on those things andof those, probably the most
important is exercise.
There's a lot of observationaldata, a little bit of
experimental data that showsthat people who exercise will
(05:15):
really live longer lives.
There was a recentobservational, there was a
longitudinal work that showedthat it was following
40-year-olds and they were usingthese wearable devices to
follow their activity and ifeveryone was as active as the
top quarter of the people in thestudy, they would have five
(05:36):
additional life years on average.
So it shows you that that's alot.
five additional life years, yeahthat's a really large effect,
if that's truly an effect.
Now it's just observationaldata.
It's not necessarilyexperimental data, though it is
longitudinal and it's very wellpowered, but at the end of the
day, we don't know exactly hownecessarily.
(05:56):
Exercise would be for sureextending life.
The idea is that it makes youmore functionally healthy.
That makes you stronger.
So it works against theage-related muscle loss that we
see in a lot of people, and it'skeeping your cardiovascular
health, your circulatory health,up and running.
Maybe there's some otherbenefits in the immune system or
(06:16):
whatnot, but it seems like theone intervention that people can
really work on because a lot ofpeople live sedentary lives is
exercise.
So that's my one recommendation.
But then the story's a littlebit more complicated from the
population level because we'vehad a lot of success over time
already improving lifeexpectancies.
(06:37):
Post-industrial revolutionpeople used to live nasty,
brutish short lives the theHobbesian construction there and
we've improved that a lot.
Speaker 1 (06:47):
Right like so you would be really old if you were
living like 150 years ago, right?
yes, yeah, that would be and andI would be like non-existent.
Yeah, so really, if you lookover the last hundred years,
there's just been this constantacceleration, but we have really
plateaued off and in the lastfew years life expectancy is
(07:11):
starting to dip and in the fieldI'm in in menopausal hormone
therapy.
When the Women's HealthInitiative was released over 22
years ago and women threw awaytheir hormones which we know and
the study itself showedlongevity by several years we
did see death rates in womenlose significant ground,
(07:36):
particularly in hysterectomizedwomen.
So that was really verydevastating.
So when you talk about addingfive years with exercise, that's
really huge and that's what Isay.
Treating hormone deficiencywill give a lot of women just
shifting that age aging curve tothe right.
So why do you think there'scountry differences In?
(07:57):
Like some countries just tendto have more older individuals
that live longer and healthier,or older individuals that live
longer and healthier.
Speaker 2 (08:10):
So I think embedded in that question is essentially
a question about blue zones.
So there's this idea that thereare areas like, say, sardinia,
which is this island in theMediterranean off of Italy, or
Okinawa in Japan, and theseareas are alleged to have a high
number of centenarians.
Speaker 1 (08:28):
Apparently, people have looked into it, that's
people for our listeners thatare 100 years or older, right.
Speaker 2 (08:33):
Yes, exactly so, extremely long-lived people.
So they've done a littledigging into these numbers and
it turns out that there's somepoor record keeping and so a lot
of the cases, and especiallylike Italy, greece, even in
Okinawa, the records for thesepeople that are supposedly alive
(08:57):
, these people are not notreally there or they didn't
really live as long as they, asthey said they did or as was
recorded.
Some of this has to do withsometimes the check keeps coming
from the government.
If you say this person's stillalive, oh, interesting.
Yes, yes so there's incentive incertain places for people to
live quite a long time, at leaston paper.
(09:19):
The Blue Zone idea has reallytaken a hit, so I don't really
know for sure if we can say.
I mean there obviously aredifferences across geographical
regions and life expectancy andI think most of that is
explained by economicdevelopment for the most part.
(09:40):
So if you go to very poorregions, their life expectancy
is lower and if you go to verypoor regions, their life
expectancy is lower and if yougo to very developed regions,
it's higher and obviouslythere's some
differences, but you're whenyou're talking about, like
saying, in america there's lotsthat is made of the deaths of
despair hypothesis, the angusdeaton hypothesis he was the
economist who won like a nobleprize for this work, I believe
(10:00):
and they argue there's a hugespike in opiate abuse related
deaths or alcohol related deathsin America relative to other
advanced nations.
There's some quibbling that canbe made about this, but that's
to some extent a real thing.
But the difference that we'retalking about is small relative
to when we're talking aboutcross-national differences
(10:21):
between wealthy countries anddeveloping countries.
Speaker 1 (10:24):
Well, we're here in the United States of America,
which is a very fortunate,wealthy country overall, but we
have a lot of obese, unhealthypeople, unfortunately, with very
high rates of metabolicsyndrome and inflammatory
conditions that increaseeverything from heart disease,
(10:45):
diabetes to dementia, arthritisand so forth.
So sometimes and, oh, of course, cancer is very much linked as
well.
So I think that there's got tobe other factors, like diet,
like we always promote theMediterranean diet and the
Italians and the Greeks ashaving long, long lives.
Speaker 2 (11:07):
So do you think some of that's?
Speaker 1 (11:08):
dietary related or is it their lifestyle?
They are more physically active, have more exposure to outside
beautiful sun, gorgeous scenery.
Speaker 2 (11:19):
I mean, I think perhaps there's something to it,
but it's on the margins andit's small and rates of obesity
are quite high across thedeveloped world in general, and
even in some less than developedplaces have fairly high obesity
rates.
It's surprising.
It's really cheap.
Calories are really prettyaccessible almost everywhere.
(11:42):
Obviously, this is not true forsome places, but in a lot of
places food is not scarceanymore, thanks to some of the
revolutions that another NobelPrize winner, norman Borlaug,
made quite a ways ago in termsof agricultural advancements and
agricultural technology, ofcourse, the Haber-Bosch process
(12:06):
as well, well before that, sovery calorically dense food that
tastes great.
Speaker 1 (12:11):
You know there's concerns.
And then anything that's brokendown quickly into simple
carbohydrates drives yourinsulin levels, which makes you
hungrier.
I always say that's why theygive you that delicious free
bread at these nice restaurants,because then you're hungry for
dessert by the end of the meal,which you're very good at
getting dessert.
Whether or not you eat bread ornot, you have quite the
(12:31):
appetite.
Speaker 2 (12:33):
So I do so.
Speaker 1 (12:36):
Peter Attia, who is a physician in the longevity
space, this is I know you gaveme his book and I'm trying to
still slog through it.
Speaker 2 (12:45):
Yes, his book is called Outlive, and so his only
advice on nutrition, for examplebecause we're kind of circling
the nutrition topic is that it'sabout energy balance, so the
calories in calories out model.
We should try our best not toeat more calories than we expend
.
And then in terms of what wemake our diet what can?
(13:08):
What comprises our diet?
The only portion that's reallyimportant to make sure is there
is the protein intake.
And he's saying that proteinintake is especially important
as you age because of thatage-related muscle loss,
age-related strength.
Speaker 1 (13:24):
Yes.
Speaker 2 (13:24):
And that's the functionality that you want to
maintain, because when you'relosing that functionality,
you're more likely to declinemore rapidly.
Speaker 1 (13:33):
Yeah, I think that certain healthy foods that are
high in protein, whether they'reeggs or red meat, unfortunately
kind of have been demonized toomuch, demonized um too much,
and so I still think there's alot we need to understand about
um nutritional, uh, genomics,and I do think there's probably
different diets that work outbetter for different people, and
(13:55):
we don't really know um to giveadvice.
We just kind of give generaladvice and I think a lot of
times the medical professiondoesn't give the best
nutritional advice,unfortunately, and and certainly
everywhere you go with fastfoods and school lunches that
aren't that healthy, it's it'slike swimming upstream.
Speaker 2 (14:15):
Yep, there are some ancestry related differences in
how calories are handled thatwe're really just beginning to
learn about thanks to largegenomic sequencing studies and
phenotyping studies, which isjust looking at the traits, and
so we're learning that peoplewho have, say, more ancestry
(14:36):
background from hunter-gathererpopulations are more thrifty.
They make better use of thecalories that they take in than
people who have more distantancestry from to
hunter-gatherers.
so obviously, people of likewest eurasian ancestry, people
(14:58):
of east asian ancestry they're alittle bit more distant
potentially than than someonewho is very recently from or
more recently we're talkinglonger time scales, of course,
but more closely related to, say, other hunter-gatherer groups,
for example, and so one of thefamous cases of this is, of
course, the pima indians, whichof course, there's some
(15:18):
scientific debates about, butthere's.
There's some pima indians thatwere in mexico and those in the
united states.
And the p Pima Indians livingin the United States were eating
a Western diet, and those thatwere living in Mexico were
eating their ancestral diet.
And the Pima Indians eating theWestern diet were getting type
2 diabetes in their late teens,early 20s, while those that were
(15:40):
in Mexico, living in anancestral fashion, were
completely healthy, for example,so there's definitely ethnic
and genetic differences for sure.
Speaker 1 (15:54):
I know that there are some nutritional genetic
researchers who are reallylooking into this researchers
who are really looking into this, looking at profiles and
dietary substances in terms ofthings like premenstrual
dysphoric disorder and there'sso much interest in this
nutrigenomics and I know thatpeople can go and have that
(16:19):
genetic testing done that tellsthem, you know, if they're at
risk for celiac or if they're atrisk for Achilles tendon
rupture or maybe if they're moreat risk for B12 deficiency or
other things.
This is all like out of pocket,but we certainly do have that
information on ourspeakingwomenshealthcom website
(16:40):
and I have had a few patientswho have wanted to have that
testing done.
I wondered if you had anyopinion about it.
Speaker 2 (16:49):
I would say that it's not ready for clinical prime
time.
Whatever insights we're getting, they're probably very noisy,
they're potentially misleading.
I would say at this time Unlessyou're one of the few people
that fall into really raresituations.
For instance, there are likehereditary obesity syndromes,
essentially.
(17:09):
So if you're someone with ahereditary obesity syndrome,
those need to be handled byspecialist teams and that's
obviously not a situation whereyou can be typically managed in
the way anyone else could be.
And there's there's a lot tolearn out there.
I'm not saying that this can'thave a future, um, and it may,
just it may not necessarily berelated to what you should eat.
(17:33):
Some of it may be like we, wemay learn that some people.
It may not be related all toweight either, for instance.
So I know you're interested in,you're very on me to make sure
I was tested to be, if I was acystic fibrosis carrier or not
right.
So the most common cysticfibrosis variant in the
population.
It's this small deletion of asingle amino acid in the CFTR
(17:58):
which is the gene for cysticfibrosis.
And that gene it's the mostcommon one and apparently
there's potentially someheterozygote advantage
associated with being a carrier.
Speaker 1 (18:10):
Interesting.
Speaker 2 (18:11):
As in, you have a lower rate of irritable bowel
syndrome.
You're much less likely to haveirritable bowel syndrome if you
are a carrier for the cysticfibrosis mutation.
Speaker 1 (18:21):
Interesting, but you didn't need to be tested because
your wife, who was pregnant,tested.
So if she's not a carrier, thenthey don't usually check the
males.
Speaker 2 (18:29):
Right.
So actually I wasn't tested,but we tested her and because
she wasn't a carrier, it didn'tmatter for me, but we obviously
pursued the testing at your, atyour urging.
Speaker 1 (18:40):
Uh-huh and oh, I didn't.
I didn't know what were theresults.
Speaker 2 (18:44):
Oh she's.
I didn't get the test is whatI'm saying because she was not
good.
You didn't need the testbecause she was negative.
Speaker 1 (18:48):
That's what I thought .
Speaker 2 (18:49):
Yeah, yeah, yeah, but I would have if she was yeah.
Speaker 1 (18:51):
Of course, of course.
It's interesting that peopleare getting so much genetic
testing done and we have columnson recreational genetic testing
and that is not adequate forcancer genetic testing and I
have so many patients, including, you know, highly educated
people, who say, oh no, I don'thave BRCA, I already had 23 and
(19:12):
me.
Speaker 2 (19:14):
Yeah, yes, those over those commercial kits, the
ancestry kits, those are what wecall sparse.
So they're.
They're not looking at thewhole sequence of a gene in any
case, they're looking at thesesmall changes at single
locations and those are calledsingle nucleotide polymorphisms,
or SNPs for short.
Yeah, so it's very sparse.
(19:34):
You're not getting whole genomeinformation, and it's now very
cheap to get whole genomeinformation.
But you should of course pursuethat in a professional setting.
Get real clinical testing done,if there's a reason to be
getting that testing done.
Speaker 1 (19:51):
Yes, and the associated counseling.
In fact, in season three I havea genetic counselor, ryan Noss,
who will be on talking aboutthe GINA law and just a lot of
the implications you know forgenetic testing.
It's not just something you goand have done.
It really needs to be done verythoughtfully and carefully and
(20:13):
with informed consent and a lotof information.
And you are listening to theSpeaking of Women's Health
podcast.
I'm your host, dr Holly Thacker, interviewing Dr Stetson
Thacker, a genomics expert andprolific reader and writer, and
we're talking about anti-aging.
Is there any anti-agingsupplements that you think
(20:35):
really work or that you wouldconsider people thinking about
or talking to their cliniciansabout?
Speaker 2 (20:43):
So I want to draw a distinction here between, again,
lifespan, which is how longsomebody's going to live, and
then their health span, which isessentially how long they live
at good health.
Speaker 1 (20:54):
Exactly, that's a very important point.
You can live a long time andsuffer and be decrepit and have
dementia and lots of problems.
Speaker 2 (21:02):
Yes, yes, exactly.
So I wouldn't say there'sanything pharmaceutical wise or
supplement wise that you cantake and you can definitively
extend your life in some way.
Now there's a lot of excitementaround drugs like metformin or
rapamycin and there's sometheoretical reasons or some
animal evidence that wouldsuggest that maybe those can
(21:22):
have some longevity benefits interms of actually extending your
lifespan, but in terms of thehuman data available to
demonstrate that it'sessentially non-existent a
little bit better in that form.
And then the rapamycin.
But there's there's reallynothing that I could point to
and say with confidence of anykind that you can take and that
(21:42):
you'll live longer in any way.
I remember when you werestarting your PhD.
Speaker 1 (21:47):
you came home one day and said hey, I think I should
start on metformin.
I'm like what are you talkingabout?
Your blood sugar is fine,you're very healthy and you have
a low body fat index and normalblood sugar.
Speaker 2 (22:06):
So what was it that impressed you so much about
metformin glucavage?
I think I was just looking toomuch or reading too much into,
say, animal and pre-clinicaldata, and I think a lot of times
we get, as scientists,sometimes overconfident about
how much those positive findingswill extrapolate to humans yeah
, that's a very important pointwe do a lot of research in mice
and mouse models, but not andmice, despite being mammals,
okay.
So they're at least in relatedto humans.
(22:28):
In that way, they're still verydifferent, you know they.
Their average lifespan is liketwo to three years.
They're nocturnal, you know,they're very, it's a very
different species.
Not everything is going totranslate in addition to that,
the types of mice that we studyin science are very different
than even like a wild mouse.
They're extremely, extremelyinbred In most cases.
(22:51):
It causes a lot of weirdnessand all this, for instance, we
probably would touch on thetopic of caloric restriction.
There is a lot of animalevidence that would say that
caloric restriction extendslifespans, and it does in these
weird mouse models.
But when you look at acrossoutbred mouse models that effect
(23:11):
kind of goes away.
So it's a little bit of anartifact of looking at these
really weird situations wherethe mice, being so inbred, has
artificially shortened theirlifespan versus like a wild
mouse has artificially shortenedtheir lifespan versus like a
wild mouse, and then when theyreduce the calories intake, in
this situation there's a littlebit of a benefit to lifespan,
but that doesn't necessarilythen generalize everything.
(23:33):
Oh, if you were a human and youjust eat less food, you're
going to live longer, and wecan't really say that.
So it's important to rememberwhatever you read as a
scientific study, it may notjump all the way up to humans,
so it's important to realizethat.
To be very confident in it, weneed to see it studied in humans
and replicated and have thestudy design done in a way that
(23:57):
allows us to confidently showthat there's a causal
relationship between thevariable that we're changing and
the effect that we're measuring.
It's just important to rememberthose things.
Speaker 1 (24:11):
Clinically.
I advise a lot of my patientswho are not pregnant, who are
fully grown, who are trying todeal with preventing weight gain
or getting weight down, whichis like one of the most
perennial problems of midlifewomen, to consider intermittent
fasting, because it does dropinsulin levels and a lot of
times it makes it easier forpeople to stick to a diet and
(24:31):
not just mindlessly snack.
Do you have any comments aboutrapamycin and why this became
like such a thing and whythere's people who are not organ
transplants that are going andseeing doctors and taking this?
Speaker 2 (24:45):
why there's people who are not organ transplants
that are going and seeingdoctors and taking this.
Yeah, it's a little crazy.
It's rapamycin, it's a potentimmunosuppressive, right?
Yes, some of these people thattake this for longevity which
these people fall into like thisbiohacker category, where
they're sort of roguespracticing science on themselves
they're sort of roguespracticing science on themselves
(25:06):
, and I mean, in some respects,it's good to have people try
things and find things out, butit's not something we can
recommend to people broadly atall.
They're taking a lot of riskonto themselves.
But so rapamycin, it inhibitsthis protein called mTOR, which
is defined by the fact that it'sa target of rapamycin.
It's the mammalian target ofrapamycin.
(25:30):
And so mTOR as a protein, itkind of sits at the center of
the metabolic function of cellsand it's a signaling molecule
but it's coordinating themetabolic activity of the cell.
Is the cell going to grow?
Is it going to participate in,basically, anabolic behavior?
Is it going to participate incatabolic behavior?
Mtor just focuses on anabolicsof the building behavior.
(25:51):
There's another protein, ampk,which focuses on the catabolic,
or the breaking things downbehavior.
And so the idea is, if you do alittle bit more breaking down,
recycle things, recycling things, you're going to rejuvenate
essentially the cellular tissue.
You're going to be able toresist the processes of aging.
Obviously there's some theoriesof aging that relate to
(26:14):
essentially protein turnover orhow much essentially related to
how much catabolism, how much ofthis recycling is going on in
the cell.
So that's what they thinkthey're promoting with this
rapamycin.
Obviously, when you're puttingsomething in your body and it's
systemic and like there's allthese effects, for instance,
like it's an immunosuppressant,like you're affecting all these
(26:35):
different tissues.
So tissues are doing differentthings.
There's a tenuous balance,there's homeostasis.
It's not simply something wecan just intervene on by
something you put into your bodythrough your mouth.
Speaker 1 (26:47):
Yeah, and there can also be a lot of off-target
effects and I think, sadly,people try to look for some
simple pill they can swallowinstead of going to bed on time,
getting their exercise, reallytrying to eat whole foods and do
a lot of the basic things whichare not always all that
exciting and do a lot of thebasic things which are not
always all that exciting.
It seems like there's just somuch out there about these
(27:08):
popular anti-aging hacks,walking barefoot outside seeing
the sunlight, which I think it'sgood for circadian rhythm.
I think there is probablysomething to it.
We have too much screen timeand we don't always have the
right lights.
There's a big craze about redlight.
I've got a column we justposted on red light therapy and
(27:29):
these subversions of extremeheat, extreme cold.
Your younger brother, myyoungest son, grayson's always
telling me get a sauna, mom, go,sit there and it'll be like a
workout without you having towork out.
Speaker 2 (27:44):
Yeah, I would say to these things that if something
subjectively makes you feel goodand there aren't many risks
associated with it, then youshould do it, and if you feel
like it's providing a functionalbenefit, then I think for the
most part, it's okay.
Now, especially with thingslike where you're not actually
putting something inside of yourbody, when it's just you know
using a sauna or exercisingbarefoot or going out in the sun
(28:07):
.
You know these are, these areminimal risks, sorts of things.
Speaker 1 (28:10):
Well, what about these cold plunges?
Didn't you go do a cold plunge?
Speaker 2 (28:16):
Yes, I mean I think the idea is yeah, the idea is
again like you're essentiallylike wrapping, ramping up stress
responses.
It's similar to exercise.
I think it's basically you'resimulating exercise in a lot of
ways and modulating inflammation.
You know, when you have aninjury, what do we do with our
injuries?
A lot of times we're putting,we're putting ice on it.
Speaker 1 (28:34):
We're putting heat on it, right, so?
Speaker 2 (28:36):
these are this tried and true methods for essentially
trying to modulate what isgoing on inflammation, wise in
the body, just to rejuvenatetissue, and so, again, I think
these are things that arecontributing to how your body is
functioning and that's why itprobably makes people
subjectively feel better.
But is it exactly going to makeyour life longer?
(28:56):
Probably not.
Speaker 1 (28:58):
Probably, not at all, probably not.
Speaker 2 (29:00):
There's some tension between making your body more
functional or more fit and thenliving longer in a lot of ways,
so we can get into that a littlebit.
For example, I think thistouches on the difference
between how long men and womenlive.
Speaker 1 (29:17):
Yes, yes, that is fascinating to me.
Speaker 2 (29:21):
Right.
So this is really widely known.
It's observed acrossessentially all societies I
think it's universal and even inother animal species most
mammals, I believe this is truefor is that the male of the
species lives a shorter lifethan the female of the species,
(29:43):
and so there's some sort oftrade-off that the males of a
species are making that iscosting them life years relative
to the female sex, and there'sdifferent theories about this,
of course, but I think it boilsdown to the sex chromosomes and
testosterone.
And the trade-off that is beingmade is men are essentially
(30:10):
ramping up to be morereproductively fit at the cost
of some robustness in the restof their system, and some of
this, of course, has abehavioral manifestation in
humans.
So, obviously, men are engagedyoung men especially are engaged
in riskier behaviors that oftenshorten their lives.
Speaker 1 (30:40):
And jobs or war or other things that obviously put
their physical bodies, which aregenerally stronger and bigger,
in part because of testosterone,into harm's way a little more
frequently.
Speaker 2 (30:53):
Yep, and some of the giveaway here is that you can do
the demographic analysis andyou can look at the mortality
rates at different age groups.
Group them by different ages.
You look at men and womenmortality rates in infancy.
It's higher for men much higherfor males.
Yes, high for males at in youth, higher for males, of course
(31:13):
yes in old age higher for males.
Of course, that's just everygroup right.
And so the question if you'reliving a normal life and you
know you've already made it tomiddle age, you're, you're
living, you're expected to livea full life.
Well, why?
Why does men still live ashorter life?
Well, I think again,testosterone is, is still
(31:33):
playing a role here.
Obviously, men die of heartdisease more often, for example,
so there's some sort ofrelationship with that, the
tissue there.
And then I also think there'ssomething that testosterone is
doing with the immune system,making men a little bit less
robust in that regard as well.
And obviously androgens havebeen associated, steroid
(31:53):
hormones in general associatedwith an immunosuppressive effect
.
So ramping up the testosteroneto be strong and ready to engage
, engage in aggressive,aggressive behaviors, to be
reproductively fit, is coming atthe cost of taking care of
those other things in the bodythere's a trade-off, that
happens.
Speaker 1 (32:11):
But you talked about the length of age versus the
functional length of age andcertainly if you walk into most
nursing homes, you're going tosee 80% female and only 20% male
.
So if you live longer butyou're infirm which we see in a
lot of women with muscle lossand memory loss and you know,
(32:33):
not all of it but a significantportion of it does relate to
hormone deficiency, which is,you know, why I focused my
career on, you know, trying toimprove people at midlife so
that they can live the secondhalf of their life more
favorably and functionally.
If you're not really gettingextra functional years, it
doesn't seem to be an advantageas a female.
Speaker 2 (32:55):
Yep, yep, yeah.
So we don't have a greatstandardized way, necessarily,
of measuring health span.
There's some subjectivity tothe measure.
So what exactly does it accountfor?
We haven't, we don't have along history of measuring health
span or a standardized way ofdoing it, whereas, like, we can
easily see when someone's bornand when someone dies.
Speaker 1 (33:16):
So it's that's the yeah, assuming the records are
correct and people aren't tryingto get their government check
right, which nowadays is alittle, at least in a place like
in the US.
Speaker 2 (33:26):
for the most part, you can trust the data.
Speaker 1 (33:29):
Oh yeah, as soon as that death certificate goes in,
the government goes and takesout a check if they've already
deposited the check for thatperson's lifespan.
I mean it's yeah, they know.
They certainly know right away,that is for sure, man.
So I always ask my patients apatients, a family history, you
know, for those people that haveit and are not adopted.
And even if they're adopted,there's still a lot of open
(33:50):
adoptions or ways that peoplecontact their biological
relatives.
But, that being said, I alwaysput a lot of uh credence in
knowing their first degreerelatives and what they died
from.
And certainly you do see thesefamilies where you know
everybody's like living intotheir nineties and they're
functioning and independent.
So there must be some geneticselection for that.
Speaker 2 (34:15):
Well, I wouldn't say genetic selection, not selection
, that's right.
Speaker 1 (34:18):
Genetic variation, you reproduce when you're
younger, not older right.
Yeah, genetic variation, that'sright.
Speaker 2 (34:23):
Although, yeah, although there could be
selection on something that thenwould also lead to longevity.
I mean, it's not that livinglong is entirely, it's not that
long lives are entirely notvisible to the evolutionary
process, but it's much less so,of course.
But you're right in thatgenetics likely plays a very
important part in extremelongevity, in that genetics
(34:45):
likely plays a very importantpart in extreme longevity.
So people who are making itover 100 years, so centenarians,
super centenarians, which arethe people who make it to 110 or
beyond, so there's very few ofthese people.
Now there's family studies,there's twin studies, there's
genome-wide association studies,there's these localized studies
(35:06):
of what certain genes do.
For instance, there's this ApoEgene, which is a lipid carrier
protein, and there's a certainvariant of this gene, the E4
allele, which is stronglyassociated with Alzheimer's
disease.
Speaker 1 (35:20):
Yes, yes, I have some patients who go and get that
testing done.
Speaker 2 (35:23):
Yes, so it's associated with.
If you're homozygous, meaningyou have two of these from both
parents, you are likely to getAlzheimer's much higher risk
versus the general populationand have a shorter life because
of that, and so that's oneexample where genes can figure
(35:44):
very strongly into longevity,and there is actually emerging
evidence and I'll talk aboutthis in future podcasts of the
interaction of menopausalhormone therapy and the
different ApoE subtypes, becauseit seems like some subtypes
seem to have more of a positiveeffect in cognition with
(36:06):
estrogen.
Yeah, so I didn't mention it,but the E2 allele of ApoE is
associated is a little bit morecommon, in centenarians, for
example.
I have to say it's again, anyallele which is typically
referring to a variant in a genethat is common in the
population.
So, like more than 1% of peoplewill be a carrier of this
(36:28):
variant of the gene.
And so when you compare itacross a population, you're
saying, like you know, 75% ofthe people who live to 100 may
have this, versus the 25% haveit who didn't live to 100, for
example.
So like what?
the actual contribution to theincrease in lifespan may be
quite small when you're lookingat these small variations, but
(36:50):
what we do know is that there,the way that long life may be
conferred genetically, may justbe having fewer deleterious
mutations overall and so therewas this recent study that was
looking at a group of AshkenaziJewish people and they of them
(37:14):
that have extremely long lives,and they were comparing them to
a control group, and they wereshowing that those that have
fewer deleterious mutations asin mutations that will
essentially inactivate the genemutations, as in mutations that
will essentially inactivate thegene they're living longer lives
.
So this is one of the mechanismsessentially their their genome
is is more robust in terms of it, they have more functionality
(37:36):
across the genome that they'renot carrying essentially
deleterious alleles and theylive longer because of this.
And this figures nicely into.
We haven't thought, we haven'ttalked about theories of aging
like why do humans age, forexample, and so one of the most
popular theories of aging iscalled the somatic theory of
aging, the somatic mutationtheory of aging.
And that's just over yourlifespan, you're accumulating
(37:57):
mutations in the DNA across thevarious cells of your body, and
accumulating those mutationscontributes to the aging process
because the cell function isregulated very tightly by
certain genetic programs, and sothe more mutations that you
accumulate in the cells, themore the genetic program of
(38:18):
those cells is going to bedysregulated.
It's the same idea of whypeople get cancer.
Speaker 1 (38:23):
And I think that's one of the reasons why there's
been these proliferations oftests that people can order
online which are very expensiveand not really validated,
looking at telomere size andaging and methylation.
So I would assume that at thispoint in time it's not ready for
prime time and you wouldn'trecommend people waste their
(38:44):
money.
Speaker 2 (38:45):
Yeah, those are not clinical grade, although there
has been evidence that showsthat the methylation pattern
that some of those tests look atis tightly correlated to the
number of somatic mutations thatare being found in a cell.
And so that would be if thesomatic mutation theory of aging
is correct, which I'm sureprobably is correct and is
(39:08):
certainly correct in some ways,but it may not be the total
story.
Speaker 1 (39:11):
The total story.
Yes, and we'll have to bringyou back to go into this some
more.
Speaker 2 (39:16):
Yes, so to the extent that it is true, it is
capturing something.
Those methylation testsprobably do capture something,
but again, there are differenttissues in your body, so these
tests probably just look at.
The methylation tests probablydo capture something, but again,
there are different tissues inyour body, so these tests
probably just look at themethylation patterns in blood,
which may be a good proxygenerally.
But again, these are all.
It's never the complete story.
(39:36):
It's not something that weshould just wholly believe and,
of course, if you've got a badresult on the test or a good
result on the test, it doesn'tmean you should just wholly
change your behavior.
Obviously, people should befocusing on living generally
healthy lives from the wisdomthat we've accumulated over time
.
Speaker 1 (39:53):
Up to this day and we know what those things are.
So, as we're wrapping this up,tell us about your new podcast
that you just launched and howpeople can listen to you and all
your intellectual insights andinteresting perspectives.
Speaker 2 (40:09):
Yes, so I recently launched a sort of general
interest, cultural commentary orspecial topics podcast with a
friend of mine which I metthrough my wife.
He's the husband of one of mywife's lifelong friends.
Wife, he's the husband of oneof my wife's lifelong friends.
He was born in Kathmandu, nepal, and so we've called our
podcast Views from Cleve Mandu,mashing up our two different
(40:32):
hometowns.
I'm from Cleveland, ohio, andso we recently started the
podcast.
Speaker 1 (40:38):
We have four episodes , I believe, we published our
fifth episode this week and yeah, so check it out at.
Yeah, you'll probably have alot wwwleavemyandoocom and I
write at Substack as well.
So we will put the podcast inthe show notes and your Substack
and by the time this airs inepisode three, I imagine you'll
(40:58):
have more than five podcasts bythen.
But that is great and so peoplecan catch that.
Speaker 2 (41:04):
We're on spotify and anywhere you get available any,
any any of the main pot uhpodcast players.
Speaker 1 (41:11):
So definitely it's on apple and it's on spotify and
it is called views from clevemandu, and you write at substack
dot com on.
You have both a scientificsubstack and then a book review
and cultural substacks, whichare very interesting.
Although I don't think youalways appreciate your mother's
(41:31):
comments, I would say that.
So, although, like I alwaystell my fellows, I've been
running this specialized women'shealth fellowship and, of
course, publishing is a big partof the academic career and
early on people don't likecriticisms of people's writing
and editing, but I do think itmakes you a more robust writer
(41:55):
and communicator.
So I would say that.
So thanks to our listeners forjoining us today and don't miss
another episode of our Speakingof Women's Health podcast, and
you can subscribe for freeanywhere where you listen on
Apple Podcasts, itunes, spotify,check out our show notes.
(42:17):
And thanks to our loyallisteners for tuning in.
And if you want to help supportthe program, please give us a
five-star rating and you canshare it with others.
It's free and you can alsodonate to
speakingofwomenshealthcom, ournonprofit.
So thanks again and we'll seeyou next time in the Sunflower
House.
Speaker 2 (42:38):
Thanks for having me, Mom.
Bye.
Speaker 1 (42:40):
Bye.
On this episode of Speaking of Women's Health we
have a recurring guest.
I'm your host, dr Holly Thacker, the Executive Director of
Speaking of Women's Health, andI am back in the Sunflower House
and joining me on this episodeis my son, dr Stetson Thacker.
No relation, of course.
(00:22):
He is my oldest son.
I talk about him all the time.
Stetson Thacker no relation, ofcourse he is my oldest son.
I talk about him all the time.
He was a guest on season oneand it was one of our most
listened to podcasts in the over100 plus that we've done.
So he joined us back in seasonone to talk about genetic
testing for cancer risk and howour genetics can help with
(00:43):
weight loss and how to continueyour weight loss resolutions
with a few simple tips.
So on this podcast we're goingto delve into anti-aging in
terms of genetics, the biology,the history that we know of the
hacks and maybe some potentialpitfalls and manipulations to
(01:05):
watch out for, since it's reallyquite a hot topic.
So a little bit about DrStetson Thacker.
He completed his PhD in genomicmedicine at Case Western
Reserve University and theCleveland Clinic Lerner College
of Medicine under the tutelageof the late great Dr Dr Karis
(01:25):
Eng, who unfortunately departedthis earth.
She was really quite ascientist and trailblazer.
So Dr Stetson studied theimpact of genetic variation on
protein structure and function,as well as clinical traits in a
cancer syndrome called P10hamartoma tumor syndrome, and I
(01:50):
certainly have the privilege ofseeing many P10 patients in my
practice courtesy of oralreferrals from Dr Eng and her
group.
Now Stetson has authored severalcolumns on speaking of women's
health.
He's actually a prolific writer.
He published a book on poetrywhen he was in high school and
(02:12):
also was a first authorpublication which is highly
cited in fertility and sterility, from research he did when he
was a high school student.
Today he is the father of twoadorable girls, my
granddaughters, who just are soexcited to see me.
By the way, when I go to theirhouse they squeal, and when
(02:33):
they're getting into my car myson wonders why do they like
your car seat?
I'm like no, they just likecoming with Mimi.
Anyway, stetson's very busy.
He works as an associateclinical variant curator for
Natara, where he interprets andclassifies genetic variants
detected by the burgeoning fieldof molecular diagnostics.
(02:55):
And Natara is a global leaderin cell-free DNA testing and
it's dedicated to oncology,women's health and organ health
all things near and dear to ourhearts.
In his free time he writes onvarious subjects, which we'll
talk about at the end of thepodcast, which include cancer,
genomics, and his substack isstetsonsubstackcom, and he just
(03:22):
started his podcast.
I guess he's kind of like hismother in that regard.
So, stetson, welcome.
Thanks for joining us againwith your busy schedule.
Speaker 2 (03:32):
Thanks for having me.
Speaker 1 (03:34):
So I thought it would be really interesting to talk
about anti-aging and what aremaybe some of the best
anti-aging strategies that ourlisteners might want to be aware
of or think about doing.
Speaker 2 (03:48):
Yeah, there's a lot of hype in the space.
The longevity space is the termof art we hear now a lot.
I think the best way to thinkabout it is from two different
perspectives.
There's the individualperspective how can I do things
to help myself live a morehealthy and longer life, which
is how most people are thinkingabout it.
(04:09):
And then there's, of course,the population level, the public
health level perspective, andwhat can we do for the the
health of the population, tohelp people have longer life
expectancies, lower mortalityrates and so on.
And so from the individualperspective, there isn't like a
ton of things that we know forsure will definitively extend
(04:31):
your life.
I mean, if we did, they'd beplastered everywhere, everybody
would be doing it all the time.
We kind of know these sort ofgeneralized health
recommendations that we havethat are you know, eat healthy,
exercise, sleep enough, thingslike this.
Speaker 1 (04:51):
Things that we focus on on so many of our podcasts,
by the way.
Speaker 2 (04:54):
Right, and it's not to say I mean, those are
important things that we shouldfocus on, living healthy lives.
We know what a healthylifestyle constitutes and we
should focus on those things andof those, probably the most
important is exercise.
There's a lot of observationaldata, a little bit of
experimental data that showsthat people who exercise will
(05:15):
really live longer lives.
There was a recentobservational, there was a
longitudinal work that showedthat it was following
40-year-olds and they were usingthese wearable devices to
follow their activity and ifeveryone was as active as the
top quarter of the people in thestudy, they would have five
(05:36):
additional life years on average.
So it shows you that that's alot.
five additional life years, yeahthat's a really large effect,
if that's truly an effect.
Now it's just observationaldata.
It's not necessarilyexperimental data, though it is
longitudinal and it's very wellpowered, but at the end of the
day, we don't know exactly hownecessarily.
(05:56):
Exercise would be for sureextending life.
The idea is that it makes youmore functionally healthy.
That makes you stronger.
So it works against theage-related muscle loss that we
see in a lot of people, and it'skeeping your cardiovascular
health, your circulatory health,up and running.
Maybe there's some otherbenefits in the immune system or
(06:16):
whatnot, but it seems like theone intervention that people can
really work on because a lot ofpeople live sedentary lives is
exercise.
So that's my one recommendation.
But then the story's a littlebit more complicated from the
population level because we'vehad a lot of success over time
already improving lifeexpectancies.
(06:37):
Post-industrial revolutionpeople used to live nasty,
brutish short lives the theHobbesian construction there and
we've improved that a lot.
Speaker 1 (06:47):
Right like so you would be really old if you were
living like 150 years ago, right?
yes, yeah, that would be and andI would be like non-existent.
Yeah, so really, if you lookover the last hundred years,
there's just been this constantacceleration, but we have really
plateaued off and in the lastfew years life expectancy is
(07:11):
starting to dip and in the fieldI'm in in menopausal hormone
therapy.
When the Women's HealthInitiative was released over 22
years ago and women threw awaytheir hormones which we know and
the study itself showedlongevity by several years we
did see death rates in womenlose significant ground,
(07:36):
particularly in hysterectomizedwomen.
So that was really verydevastating.
So when you talk about addingfive years with exercise, that's
really huge and that's what Isay.
Treating hormone deficiencywill give a lot of women just
shifting that age aging curve tothe right.
So why do you think there'scountry differences In?
(07:57):
Like some countries just tendto have more older individuals
that live longer and healthier,or older individuals that live
longer and healthier.
Speaker 2 (08:10):
So I think embedded in that question is essentially
a question about blue zones.
So there's this idea that thereare areas like, say, sardinia,
which is this island in theMediterranean off of Italy, or
Okinawa in Japan, and theseareas are alleged to have a high
number of centenarians.
Speaker 1 (08:28):
Apparently, people have looked into it, that's
people for our listeners thatare 100 years or older, right.
Speaker 2 (08:33):
Yes, exactly so, extremely long-lived people.
So they've done a littledigging into these numbers and
it turns out that there's somepoor record keeping and so a lot
of the cases, and especiallylike Italy, greece, even in
Okinawa, the records for thesepeople that are supposedly alive
(08:57):
, these people are not notreally there or they didn't
really live as long as they, asthey said they did or as was
recorded.
Some of this has to do withsometimes the check keeps coming
from the government.
If you say this person's stillalive, oh, interesting.
Yes, yes so there's incentive incertain places for people to
live quite a long time, at leaston paper.
(09:19):
The Blue Zone idea has reallytaken a hit, so I don't really
know for sure if we can say.
I mean there obviously aredifferences across geographical
regions and life expectancy andI think most of that is
explained by economicdevelopment for the most part.
(09:40):
So if you go to very poorregions, their life expectancy
is lower and if you go to verypoor regions, their life
expectancy is lower and if yougo to very developed regions,
it's higher and obviouslythere's some
differences, but you're whenyou're talking about, like
saying, in america there's lotsthat is made of the deaths of
despair hypothesis, the angusdeaton hypothesis he was the
economist who won like a nobleprize for this work, I believe
(10:00):
and they argue there's a hugespike in opiate abuse related
deaths or alcohol related deathsin America relative to other
advanced nations.
There's some quibbling that canbe made about this, but that's
to some extent a real thing.
But the difference that we'retalking about is small relative
to when we're talking aboutcross-national differences
(10:21):
between wealthy countries anddeveloping countries.
Speaker 1 (10:24):
Well, we're here in the United States of America,
which is a very fortunate,wealthy country overall, but we
have a lot of obese, unhealthypeople, unfortunately, with very
high rates of metabolicsyndrome and inflammatory
conditions that increaseeverything from heart disease,
(10:45):
diabetes to dementia, arthritisand so forth.
So sometimes and, oh, of course, cancer is very much linked as
well.
So I think that there's got tobe other factors, like diet,
like we always promote theMediterranean diet and the
Italians and the Greeks ashaving long, long lives.
Speaker 2 (11:07):
So do you think some of that's?
Speaker 1 (11:08):
dietary related or is it their lifestyle?
They are more physically active, have more exposure to outside
beautiful sun, gorgeous scenery.
Speaker 2 (11:19):
I mean, I think perhaps there's something to it,
but it's on the margins andit's small and rates of obesity
are quite high across thedeveloped world in general, and
even in some less than developedplaces have fairly high obesity
rates.
It's surprising.
It's really cheap.
Calories are really prettyaccessible almost everywhere.
(11:42):
Obviously, this is not true forsome places, but in a lot of
places food is not scarceanymore, thanks to some of the
revolutions that another NobelPrize winner, norman Borlaug,
made quite a ways ago in termsof agricultural advancements and
agricultural technology, ofcourse, the Haber-Bosch process
(12:06):
as well, well before that, sovery calorically dense food that
tastes great.
Speaker 1 (12:11):
You know there's concerns.
And then anything that's brokendown quickly into simple
carbohydrates drives yourinsulin levels, which makes you
hungrier.
I always say that's why theygive you that delicious free
bread at these nice restaurants,because then you're hungry for
dessert by the end of the meal,which you're very good at
getting dessert.
Whether or not you eat bread ornot, you have quite the
(12:31):
appetite.
Speaker 2 (12:33):
So I do so.
Speaker 1 (12:36):
Peter Attia, who is a physician in the longevity
space, this is I know you gaveme his book and I'm trying to
still slog through it.
Speaker 2 (12:45):
Yes, his book is called Outlive, and so his only
advice on nutrition, for examplebecause we're kind of circling
the nutrition topic is that it'sabout energy balance, so the
calories in calories out model.
We should try our best not toeat more calories than we expend
.
And then in terms of what wemake our diet what can?
(13:08):
What comprises our diet?
The only portion that's reallyimportant to make sure is there
is the protein intake.
And he's saying that proteinintake is especially important
as you age because of thatage-related muscle loss,
age-related strength.
Speaker 1 (13:24):
Yes.
Speaker 2 (13:24):
And that's the functionality that you want to
maintain, because when you'relosing that functionality,
you're more likely to declinemore rapidly.
Speaker 1 (13:33):
Yeah, I think that certain healthy foods that are
high in protein, whether they'reeggs or red meat, unfortunately
kind of have been demonized toomuch, demonized um too much,
and so I still think there's alot we need to understand about
um nutritional, uh, genomics,and I do think there's probably
different diets that work outbetter for different people, and
(13:55):
we don't really know um to giveadvice.
We just kind of give generaladvice and I think a lot of
times the medical professiondoesn't give the best
nutritional advice,unfortunately, and and certainly
everywhere you go with fastfoods and school lunches that
aren't that healthy, it's it'slike swimming upstream.
Speaker 2 (14:15):
Yep, there are some ancestry related differences in
how calories are handled thatwe're really just beginning to
learn about thanks to largegenomic sequencing studies and
phenotyping studies, which isjust looking at the traits, and
so we're learning that peoplewho have, say, more ancestry
(14:36):
background from hunter-gathererpopulations are more thrifty.
They make better use of thecalories that they take in than
people who have more distantancestry from to
hunter-gatherers.
so obviously, people of likewest eurasian ancestry, people
(14:58):
of east asian ancestry they're alittle bit more distant
potentially than than someonewho is very recently from or
more recently we're talkinglonger time scales, of course,
but more closely related to, say, other hunter-gatherer groups,
for example, and so one of thefamous cases of this is, of
course, the pima indians, whichof course, there's some
(15:18):
scientific debates about, butthere's.
There's some pima indians thatwere in mexico and those in the
united states.
And the p Pima Indians livingin the United States were eating
a Western diet, and those thatwere living in Mexico were
eating their ancestral diet.
And the Pima Indians eating theWestern diet were getting type
2 diabetes in their late teens,early 20s, while those that were
(15:40):
in Mexico, living in anancestral fashion, were
completely healthy, for example,so there's definitely ethnic
and genetic differences for sure.
Speaker 1 (15:54):
I know that there are some nutritional genetic
researchers who are reallylooking into this researchers
who are really looking into this, looking at profiles and
dietary substances in terms ofthings like premenstrual
dysphoric disorder and there'sso much interest in this
nutrigenomics and I know thatpeople can go and have that
(16:19):
genetic testing done that tellsthem, you know, if they're at
risk for celiac or if they're atrisk for Achilles tendon
rupture or maybe if they're moreat risk for B12 deficiency or
other things.
This is all like out of pocket,but we certainly do have that
information on ourspeakingwomenshealthcom website
(16:40):
and I have had a few patientswho have wanted to have that
testing done.
I wondered if you had anyopinion about it.
Speaker 2 (16:49):
I would say that it's not ready for clinical prime
time.
Whatever insights we're getting, they're probably very noisy,
they're potentially misleading.
I would say at this time Unlessyou're one of the few people
that fall into really raresituations.
For instance, there are likehereditary obesity syndromes,
essentially.
(17:09):
So if you're someone with ahereditary obesity syndrome,
those need to be handled byspecialist teams and that's
obviously not a situation whereyou can be typically managed in
the way anyone else could be.
And there's there's a lot tolearn out there.
I'm not saying that this can'thave a future, um, and it may,
just it may not necessarily berelated to what you should eat.
(17:33):
Some of it may be like we, wemay learn that some people.
It may not be related all toweight either, for instance.
So I know you're interested in,you're very on me to make sure
I was tested to be, if I was acystic fibrosis carrier or not
right.
So the most common cysticfibrosis variant in the
population.
It's this small deletion of asingle amino acid in the CFTR
(17:58):
which is the gene for cysticfibrosis.
And that gene it's the mostcommon one and apparently
there's potentially someheterozygote advantage
associated with being a carrier.
Speaker 1 (18:10):
Interesting.
Speaker 2 (18:11):
As in, you have a lower rate of irritable bowel
syndrome.
You're much less likely to haveirritable bowel syndrome if you
are a carrier for the cysticfibrosis mutation.
Speaker 1 (18:21):
Interesting, but you didn't need to be tested because
your wife, who was pregnant,tested.
So if she's not a carrier, thenthey don't usually check the
males.
Speaker 2 (18:29):
Right.
So actually I wasn't tested,but we tested her and because
she wasn't a carrier, it didn'tmatter for me, but we obviously
pursued the testing at your, atyour urging.
Speaker 1 (18:40):
Uh-huh and oh, I didn't.
I didn't know what were theresults.
Speaker 2 (18:44):
Oh she's.
I didn't get the test is whatI'm saying because she was not
good.
You didn't need the testbecause she was negative.
Speaker 1 (18:48):
That's what I thought .
Speaker 2 (18:49):
Yeah, yeah, yeah, but I would have if she was yeah.
Speaker 1 (18:51):
Of course, of course.
It's interesting that peopleare getting so much genetic
testing done and we have columnson recreational genetic testing
and that is not adequate forcancer genetic testing and I
have so many patients, including, you know, highly educated
people, who say, oh no, I don'thave BRCA, I already had 23 and
(19:12):
me.
Speaker 2 (19:14):
Yeah, yes, those over those commercial kits, the
ancestry kits, those are what wecall sparse.
So they're.
They're not looking at thewhole sequence of a gene in any
case, they're looking at thesesmall changes at single
locations and those are calledsingle nucleotide polymorphisms,
or SNPs for short.
Yeah, so it's very sparse.
(19:34):
You're not getting whole genomeinformation, and it's now very
cheap to get whole genomeinformation.
But you should of course pursuethat in a professional setting.
Get real clinical testing done,if there's a reason to be
getting that testing done.
Speaker 1 (19:51):
Yes, and the associated counseling.
In fact, in season three I havea genetic counselor, ryan Noss,
who will be on talking aboutthe GINA law and just a lot of
the implications you know forgenetic testing.
It's not just something you goand have done.
It really needs to be done verythoughtfully and carefully and
(20:13):
with informed consent and a lotof information.
And you are listening to theSpeaking of Women's Health
podcast.
I'm your host, dr Holly Thacker, interviewing Dr Stetson
Thacker, a genomics expert andprolific reader and writer, and
we're talking about anti-aging.
Is there any anti-agingsupplements that you think
(20:35):
really work or that you wouldconsider people thinking about
or talking to their cliniciansabout?
Speaker 2 (20:43):
So I want to draw a distinction here between, again,
lifespan, which is how longsomebody's going to live, and
then their health span, which isessentially how long they live
at good health.
Speaker 1 (20:54):
Exactly, that's a very important point.
You can live a long time andsuffer and be decrepit and have
dementia and lots of problems.
Speaker 2 (21:02):
Yes, yes, exactly.
So I wouldn't say there'sanything pharmaceutical wise or
supplement wise that you cantake and you can definitively
extend your life in some way.
Now there's a lot of excitementaround drugs like metformin or
rapamycin and there's sometheoretical reasons or some
animal evidence that wouldsuggest that maybe those can
(21:22):
have some longevity benefits interms of actually extending your
lifespan, but in terms of thehuman data available to
demonstrate that it'sessentially non-existent a
little bit better in that form.
And then the rapamycin.
But there's there's reallynothing that I could point to
and say with confidence of anykind that you can take and that
(21:42):
you'll live longer in any way.
I remember when you werestarting your PhD.
Speaker 1 (21:47):
you came home one day and said hey, I think I should
start on metformin.
I'm like what are you talkingabout?
Your blood sugar is fine,you're very healthy and you have
a low body fat index and normalblood sugar.
Speaker 2 (22:06):
So what was it that impressed you so much about
metformin glucavage?
I think I was just looking toomuch or reading too much into,
say, animal and pre-clinicaldata, and I think a lot of times
we get, as scientists,sometimes overconfident about
how much those positive findingswill extrapolate to humans yeah
, that's a very important pointwe do a lot of research in mice
and mouse models, but not andmice, despite being mammals,
okay.
So they're at least in relatedto humans.
(22:28):
In that way, they're still verydifferent, you know they.
Their average lifespan is liketwo to three years.
They're nocturnal, you know,they're very, it's a very
different species.
Not everything is going totranslate in addition to that,
the types of mice that we studyin science are very different
than even like a wild mouse.
They're extremely, extremelyinbred In most cases.
(22:51):
It causes a lot of weirdnessand all this, for instance, we
probably would touch on thetopic of caloric restriction.
There is a lot of animalevidence that would say that
caloric restriction extendslifespans, and it does in these
weird mouse models.
But when you look at acrossoutbred mouse models that effect
(23:11):
kind of goes away.
So it's a little bit of anartifact of looking at these
really weird situations wherethe mice, being so inbred, has
artificially shortened theirlifespan versus like a wild
mouse has artificially shortenedtheir lifespan versus like a
wild mouse, and then when theyreduce the calories intake, in
this situation there's a littlebit of a benefit to lifespan,
but that doesn't necessarilythen generalize everything.
(23:33):
Oh, if you were a human and youjust eat less food, you're
going to live longer, and wecan't really say that.
So it's important to rememberwhatever you read as a
scientific study, it may notjump all the way up to humans,
so it's important to realizethat.
To be very confident in it, weneed to see it studied in humans
and replicated and have thestudy design done in a way that
(23:57):
allows us to confidently showthat there's a causal
relationship between thevariable that we're changing and
the effect that we're measuring.
It's just important to rememberthose things.
Speaker 1 (24:11):
Clinically.
I advise a lot of my patientswho are not pregnant, who are
fully grown, who are trying todeal with preventing weight gain
or getting weight down, whichis like one of the most
perennial problems of midlifewomen, to consider intermittent
fasting, because it does dropinsulin levels and a lot of
times it makes it easier forpeople to stick to a diet and
(24:31):
not just mindlessly snack.
Do you have any comments aboutrapamycin and why this became
like such a thing and whythere's people who are not organ
transplants that are going andseeing doctors and taking this?
Speaker 2 (24:45):
why there's people who are not organ transplants
that are going and seeingdoctors and taking this.
Yeah, it's a little crazy.
It's rapamycin, it's a potentimmunosuppressive, right?
Yes, some of these people thattake this for longevity which
these people fall into like thisbiohacker category, where
they're sort of roguespracticing science on themselves
they're sort of roguespracticing science on themselves
(25:06):
, and I mean, in some respects,it's good to have people try
things and find things out, butit's not something we can
recommend to people broadly atall.
They're taking a lot of riskonto themselves.
But so rapamycin, it inhibitsthis protein called mTOR, which
is defined by the fact that it'sa target of rapamycin.
It's the mammalian target ofrapamycin.
(25:30):
And so mTOR as a protein, itkind of sits at the center of
the metabolic function of cellsand it's a signaling molecule
but it's coordinating themetabolic activity of the cell.
Is the cell going to grow?
Is it going to participate in,basically, anabolic behavior?
Is it going to participate incatabolic behavior?
Mtor just focuses on anabolicsof the building behavior.
(25:51):
There's another protein, ampk,which focuses on the catabolic,
or the breaking things downbehavior.
And so the idea is, if you do alittle bit more breaking down,
recycle things, recycling things, you're going to rejuvenate
essentially the cellular tissue.
You're going to be able toresist the processes of aging.
Obviously there's some theoriesof aging that relate to
(26:14):
essentially protein turnover orhow much essentially related to
how much catabolism, how much ofthis recycling is going on in
the cell.
So that's what they thinkthey're promoting with this
rapamycin.
Obviously, when you're puttingsomething in your body and it's
systemic and like there's allthese effects, for instance,
like it's an immunosuppressant,like you're affecting all these
(26:35):
different tissues.
So tissues are doing differentthings.
There's a tenuous balance,there's homeostasis.
It's not simply something wecan just intervene on by
something you put into your bodythrough your mouth.
Speaker 1 (26:47):
Yeah, and there can also be a lot of off-target
effects and I think, sadly,people try to look for some
simple pill they can swallowinstead of going to bed on time,
getting their exercise, reallytrying to eat whole foods and do
a lot of the basic things whichare not always all that
exciting and do a lot of thebasic things which are not
always all that exciting.
It seems like there's just somuch out there about these
(27:08):
popular anti-aging hacks,walking barefoot outside seeing
the sunlight, which I think it'sgood for circadian rhythm.
I think there is probablysomething to it.
We have too much screen timeand we don't always have the
right lights.
There's a big craze about redlight.
I've got a column we justposted on red light therapy and
(27:29):
these subversions of extremeheat, extreme cold.
Your younger brother, myyoungest son, grayson's always
telling me get a sauna, mom, go,sit there and it'll be like a
workout without you having towork out.
Speaker 2 (27:44):
Yeah, I would say to these things that if something
subjectively makes you feel goodand there aren't many risks
associated with it, then youshould do it, and if you feel
like it's providing a functionalbenefit, then I think for the
most part, it's okay.
Now, especially with thingslike where you're not actually
putting something inside of yourbody, when it's just you know
using a sauna or exercisingbarefoot or going out in the sun
(28:07):
.
You know these are, these areminimal risks, sorts of things.
Speaker 1 (28:10):
Well, what about these cold plunges?
Didn't you go do a cold plunge?
Speaker 2 (28:16):
Yes, I mean I think the idea is yeah, the idea is
again like you're essentiallylike wrapping, ramping up stress
responses.
It's similar to exercise.
I think it's basically you'resimulating exercise in a lot of
ways and modulating inflammation.
You know, when you have aninjury, what do we do with our
injuries?
A lot of times we're putting,we're putting ice on it.
Speaker 1 (28:34):
We're putting heat on it, right, so?
Speaker 2 (28:36):
these are this tried and true methods for essentially
trying to modulate what isgoing on inflammation, wise in
the body, just to rejuvenatetissue, and so, again, I think
these are things that arecontributing to how your body is
functioning and that's why itprobably makes people
subjectively feel better.
But is it exactly going to makeyour life longer?
(28:56):
Probably not.
Speaker 1 (28:58):
Probably, not at all, probably not.
Speaker 2 (29:00):
There's some tension between making your body more
functional or more fit and thenliving longer in a lot of ways,
so we can get into that a littlebit.
For example, I think thistouches on the difference
between how long men and womenlive.
Speaker 1 (29:17):
Yes, yes, that is fascinating to me.
Speaker 2 (29:21):
Right.
So this is really widely known.
It's observed acrossessentially all societies I
think it's universal and even inother animal species most
mammals, I believe this is truefor is that the male of the
species lives a shorter lifethan the female of the species,
(29:43):
and so there's some sort oftrade-off that the males of a
species are making that iscosting them life years relative
to the female sex, and there'sdifferent theories about this,
of course, but I think it boilsdown to the sex chromosomes and
testosterone.
And the trade-off that is beingmade is men are essentially
(30:10):
ramping up to be morereproductively fit at the cost
of some robustness in the restof their system, and some of
this, of course, has abehavioral manifestation in
humans.
So, obviously, men are engagedyoung men especially are engaged
in riskier behaviors that oftenshorten their lives.
Speaker 1 (30:40):
And jobs or war or other things that obviously put
their physical bodies, which aregenerally stronger and bigger,
in part because of testosterone,into harm's way a little more
frequently.
Speaker 2 (30:53):
Yep, and some of the giveaway here is that you can do
the demographic analysis andyou can look at the mortality
rates at different age groups.
Group them by different ages.
You look at men and womenmortality rates in infancy.
It's higher for men much higherfor males.
Yes, high for males at in youth, higher for males, of course
(31:13):
yes in old age higher for males.
Of course, that's just everygroup right.
And so the question if you'reliving a normal life and you
know you've already made it tomiddle age, you're, you're
living, you're expected to livea full life.
Well, why?
Why does men still live ashorter life?
Well, I think again,testosterone is, is still
(31:33):
playing a role here.
Obviously, men die of heartdisease more often, for example,
so there's some sort ofrelationship with that, the
tissue there.
And then I also think there'ssomething that testosterone is
doing with the immune system,making men a little bit less
robust in that regard as well.
And obviously androgens havebeen associated, steroid
(31:53):
hormones in general associatedwith an immunosuppressive effect
.
So ramping up the testosteroneto be strong and ready to engage
, engage in aggressive,aggressive behaviors, to be
reproductively fit, is coming atthe cost of taking care of
those other things in the bodythere's a trade-off, that
happens.
Speaker 1 (32:11):
But you talked about the length of age versus the
functional length of age andcertainly if you walk into most
nursing homes, you're going tosee 80% female and only 20% male
.
So if you live longer butyou're infirm which we see in a
lot of women with muscle lossand memory loss and you know,
(32:33):
not all of it but a significantportion of it does relate to
hormone deficiency, which is,you know, why I focused my
career on, you know, trying toimprove people at midlife so
that they can live the secondhalf of their life more
favorably and functionally.
If you're not really gettingextra functional years, it
doesn't seem to be an advantageas a female.
Speaker 2 (32:55):
Yep, yep, yeah.
So we don't have a greatstandardized way, necessarily,
of measuring health span.
There's some subjectivity tothe measure.
So what exactly does it accountfor?
We haven't, we don't have along history of measuring health
span or a standardized way ofdoing it, whereas, like, we can
easily see when someone's bornand when someone dies.
Speaker 1 (33:16):
So it's that's the yeah, assuming the records are
correct and people aren't tryingto get their government check
right, which nowadays is alittle, at least in a place like
in the US.
Speaker 2 (33:26):
for the most part, you can trust the data.
Speaker 1 (33:29):
Oh yeah, as soon as that death certificate goes in,
the government goes and takesout a check if they've already
deposited the check for thatperson's lifespan.
I mean it's yeah, they know.
They certainly know right away,that is for sure, man.
So I always ask my patients apatients, a family history, you
know, for those people that haveit and are not adopted.
And even if they're adopted,there's still a lot of open
(33:50):
adoptions or ways that peoplecontact their biological
relatives.
But, that being said, I alwaysput a lot of uh credence in
knowing their first degreerelatives and what they died
from.
And certainly you do see thesefamilies where you know
everybody's like living intotheir nineties and they're
functioning and independent.
So there must be some geneticselection for that.
Speaker 2 (34:15):
Well, I wouldn't say genetic selection, not selection
, that's right.
Speaker 1 (34:18):
Genetic variation, you reproduce when you're
younger, not older right.
Yeah, genetic variation, that'sright.
Speaker 2 (34:23):
Although, yeah, although there could be
selection on something that thenwould also lead to longevity.
I mean, it's not that livinglong is entirely, it's not that
long lives are entirely notvisible to the evolutionary
process, but it's much less so,of course.
But you're right in thatgenetics likely plays a very
important part in extremelongevity, in that genetics
(34:45):
likely plays a very importantpart in extreme longevity.
So people who are making itover 100 years, so centenarians,
super centenarians, which arethe people who make it to 110 or
beyond, so there's very few ofthese people.
Now there's family studies,there's twin studies, there's
genome-wide association studies,there's these localized studies
(35:06):
of what certain genes do.
For instance, there's this ApoEgene, which is a lipid carrier
protein, and there's a certainvariant of this gene, the E4
allele, which is stronglyassociated with Alzheimer's
disease.
Speaker 1 (35:20):
Yes, yes, I have some patients who go and get that
testing done.
Speaker 2 (35:23):
Yes, so it's associated with.
If you're homozygous, meaningyou have two of these from both
parents, you are likely to getAlzheimer's much higher risk
versus the general populationand have a shorter life because
of that, and so that's oneexample where genes can figure
(35:44):
very strongly into longevity,and there is actually emerging
evidence and I'll talk aboutthis in future podcasts of the
interaction of menopausalhormone therapy and the
different ApoE subtypes, becauseit seems like some subtypes
seem to have more of a positiveeffect in cognition with
(36:06):
estrogen.
Yeah, so I didn't mention it,but the E2 allele of ApoE is
associated is a little bit morecommon, in centenarians, for
example.
I have to say it's again, anyallele which is typically
referring to a variant in a genethat is common in the
population.
So, like more than 1% of peoplewill be a carrier of this
(36:28):
variant of the gene.
And so when you compare itacross a population, you're
saying, like you know, 75% ofthe people who live to 100 may
have this, versus the 25% haveit who didn't live to 100, for
example.
So like what?
the actual contribution to theincrease in lifespan may be
quite small when you're lookingat these small variations, but
(36:50):
what we do know is that there,the way that long life may be
conferred genetically, may justbe having fewer deleterious
mutations overall and so therewas this recent study that was
looking at a group of AshkenaziJewish people and they of them
(37:14):
that have extremely long lives,and they were comparing them to
a control group, and they wereshowing that those that have
fewer deleterious mutations asin mutations that will
essentially inactivate the genemutations, as in mutations that
will essentially inactivate thegene they're living longer lives
.
So this is one of the mechanismsessentially their their genome
is is more robust in terms of it, they have more functionality
(37:36):
across the genome that they'renot carrying essentially
deleterious alleles and theylive longer because of this.
And this figures nicely into.
We haven't thought, we haven'ttalked about theories of aging
like why do humans age, forexample, and so one of the most
popular theories of aging iscalled the somatic theory of
aging, the somatic mutationtheory of aging.
And that's just over yourlifespan, you're accumulating
(37:57):
mutations in the DNA across thevarious cells of your body, and
accumulating those mutationscontributes to the aging process
because the cell function isregulated very tightly by
certain genetic programs, and sothe more mutations that you
accumulate in the cells, themore the genetic program of
(38:18):
those cells is going to bedysregulated.
It's the same idea of whypeople get cancer.
Speaker 1 (38:23):
And I think that's one of the reasons why there's
been these proliferations oftests that people can order
online which are very expensiveand not really validated,
looking at telomere size andaging and methylation.
So I would assume that at thispoint in time it's not ready for
prime time and you wouldn'trecommend people waste their
(38:44):
money.
Speaker 2 (38:45):
Yeah, those are not clinical grade, although there
has been evidence that showsthat the methylation pattern
that some of those tests look atis tightly correlated to the
number of somatic mutations thatare being found in a cell.
And so that would be if thesomatic mutation theory of aging
is correct, which I'm sureprobably is correct and is
(39:08):
certainly correct in some ways,but it may not be the total
story.
Speaker 1 (39:11):
The total story.
Yes, and we'll have to bringyou back to go into this some
more.
Speaker 2 (39:16):
Yes, so to the extent that it is true, it is
capturing something.
Those methylation testsprobably do capture something,
but again, there are differenttissues in your body, so these
tests probably just look at.
The methylation tests probablydo capture something, but again,
there are different tissues inyour body, so these tests
probably just look at themethylation patterns in blood,
which may be a good proxygenerally.
But again, these are all.
It's never the complete story.
(39:36):
It's not something that weshould just wholly believe and,
of course, if you've got a badresult on the test or a good
result on the test, it doesn'tmean you should just wholly
change your behavior.
Obviously, people should befocusing on living generally
healthy lives from the wisdomthat we've accumulated over time
.
Speaker 1 (39:53):
Up to this day and we know what those things are.
So, as we're wrapping this up,tell us about your new podcast
that you just launched and howpeople can listen to you and all
your intellectual insights andinteresting perspectives.
Speaker 2 (40:09):
Yes, so I recently launched a sort of general
interest, cultural commentary orspecial topics podcast with a
friend of mine which I metthrough my wife.
He's the husband of one of mywife's lifelong friends.
Wife, he's the husband of oneof my wife's lifelong friends.
He was born in Kathmandu, nepal, and so we've called our
podcast Views from Cleve Mandu,mashing up our two different
(40:32):
hometowns.
I'm from Cleveland, ohio, andso we recently started the
podcast.
Speaker 1 (40:38):
We have four episodes , I believe, we published our
fifth episode this week and yeah, so check it out at.
Yeah, you'll probably have alot wwwleavemyandoocom and I
write at Substack as well.
So we will put the podcast inthe show notes and your Substack
and by the time this airs inepisode three, I imagine you'll
(40:58):
have more than five podcasts bythen.
But that is great and so peoplecan catch that.
Speaker 2 (41:04):
We're on spotify and anywhere you get available any,
any any of the main pot uhpodcast players.
Speaker 1 (41:11):
So definitely it's on apple and it's on spotify and
it is called views from clevemandu, and you write at substack
dot com on.
You have both a scientificsubstack and then a book review
and cultural substacks, whichare very interesting.
Although I don't think youalways appreciate your mother's
(41:31):
comments, I would say that.
So, although, like I alwaystell my fellows, I've been
running this specialized women'shealth fellowship and, of
course, publishing is a big partof the academic career and
early on people don't likecriticisms of people's writing
and editing, but I do think itmakes you a more robust writer
(41:55):
and communicator.
So I would say that.
So thanks to our listeners forjoining us today and don't miss
another episode of our Speakingof Women's Health podcast, and
you can subscribe for freeanywhere where you listen on
Apple Podcasts, itunes, spotify,check out our show notes.
(42:17):
And thanks to our loyallisteners for tuning in.
And if you want to help supportthe program, please give us a
five-star rating and you canshare it with others.
It's free and you can alsodonate to
speakingofwomenshealthcom, ournonprofit.
So thanks again and we'll seeyou next time in the Sunflower
House.
Speaker 2 (42:38):
Thanks for having me, Mom.
Bye.
Speaker 1 (42:40):
Bye.
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