May 6, 2025 • 32 mins
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Health Affairs' Senior Deputy Editor Rob Lott interviews Eric Topol, Executive Vice President of Scripps Research, on his new book, Super Agers, which provides an evidence-based approach on extending healthy lifespans.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Rob Lott (00:31):
Hello, and welcome to A Health I'm your host, Rob
Lott. Friends, it's another oneof our very special episodes. As
you know, typically on a healthodyssey, we feature the authors
of recent health affairsarticles to dig in on their
(00:54):
research and explore theirfindings. But about once a
month, our producer Jeff lets uspush the boundaries a bit to
bring on a special guest fromsomewhere perhaps a little more
exotic in the health policyuniverse to talk about their
experiences in the field and toreflect on their own
(01:14):
understanding of this verystrange moment in time. Today,
we're so lucky to be here withthe one and only Doctor.
Eric Topol, Director and Founderof the Scripps Research
Translational Institute. Doctor.Topol is one of the leading
voices for reason, transparency,and optimism as driving forces
(01:37):
of the biomedical enterprise. Heis a principal investigator of
the All of Us Research Program,a huge precision medicine
initiative created by Congressand funded by the NIH. He's a
practicing cardiologist, andwith all of his free time, the
author of three bestsellingworks of nonfiction about
(02:00):
health, medicine, andtechnology.
Now his fourth book publishedjust this month is titled An
Evidence Based Approach toLongevity. Doctor. Eric Topol,
welcome to A Health Odyssey.
Eric Topol (02:15):
Thanks so much. It's great to be with you.
Rob Lott (02:17):
So in a moment, we'll discuss the new book. But first,
you've authored a number ofbooks on precision medicine, AI,
the bleeding edges of thesetechnologies. Can you tell us a
little bit about your journeyfrom aspiring doctor to sort of
leading voice on some of thesereally cutting edge issues?
Eric Topol (02:40):
Well, thank you. I mean, I think the thing for me
is always to try to take atleast my best shot for where are
we headed in medicine. And we'rein some ways going back to
college, I mean, genetics, weweren't quite ready until we
could sequence the genome. Butthat's what led in the 1990s,
(03:01):
when I was at Cleveland Clinicto set up the first
cardiovascular biobank, whereover 10,000 people back then,
where we had their gene assaysfor what got them into the
cardiovascular world of healthissues. And so basically, what
(03:22):
happened was in sequence, I gotinto genetics again, and then
sensors because that was, it'snot just the genes, there's a
lot more to us than that.
And then this whole theme ofindividualized medicine, where
the more layers of data on eachof us, the better we're going to
do in terms of ultimatelypreventing diseases. That's what
(03:44):
the new book is about. But it'sbasically been a very, for me, a
logical building up of firstdigitizing human beings with
these things we're just talkingabout, then democratizing,
because once you have everythingdigitized, doctors are no longer
in control of everything, whichis good. And then the book Deep
(04:07):
Medicine, that was the last bookI wrote was about AI and how
that ultimately with new modelsthat we needed and we have now
is going to be transformative.So we've got the AI models and
now what are we going to do?
And that's kind of, I thinkwhere the excitement lies for me
and hopefully the medicalcommunity and patients as well.
Rob Lott (04:30):
So I think one place where all of these different
trends come together is the Allof Us Research Program, which
was created as part of thetwenty first Century Cures Act,
which believe it or not was nineyears ago. And generally,
(04:52):
correct me if I'm wrong here,the idea is to collect genetic
and health data for upwards of amillion participants with the
goal of opening the door topotentially new innovations in
precision medicine, movingbeyond sort of one size fits all
approach to clinical trials andthe findings of clinical
(05:13):
research. Enrollment started in2017. And here we are a number
of years later, a full blownpandemic later. Where do things
stand?
What have you seen change? Whathave you learned in the last few
years from that project?
Eric Topol (05:30):
Yeah, it's been, I think the biggest commitment for
a singular or single project inthe history of American medical
research billions of dollars.Its real origin was
interestingly with then SenatorObama, who pressed for something
like this, and then FrancisCollins, the NIH director. So it
(05:50):
got off the ground just as yousaid, and now has over 850,000
very diverse participants. Abouthalf are not European ancestry.
So it's very different than theUK Biobank or other biobanks
around the world.
But what's noteworthy is themajority have had whole genome
(06:13):
sequencing and progressivelythey're getting their data. So
that is one layer of data. We'vealso had sensors in a large
proportion. And the intent isgoing forward, we'll have many
other layers of data to helpguide these participants to get
(06:34):
better health care. The onlyproblem is our funding has
gotten substantially reduced.
The Cures Act, the Congress andwhatnot, and our current cuts.
So it may not be as quiteambitious as originally laid
out. But at least it's a verylarge population, uniquely
(06:55):
diverse, that has rich data, andit's being made to the entire
world of medical researchers. Sojust like the UK Biobank, a lot
of good things will come from itand already have.
Rob Lott (07:07):
Well, that's a great segue. Can you maybe give us an
example or two of somethingexciting or promising that's
come out of this projectalready?
Eric Topol (07:17):
Well, we've already learned of some new gene
variants that account for someof the most important age
related diseases, includingcancer and cardiovascular or
neurodegenerative. And that wascritical because previous to the
all of us, so many of thestudies for genetics were in
(07:38):
predominantly white and Europeanancestry. So this multi ancestry
capability made a hugedifference. But the, for
example, we distributed Fitbitsvery widely throughout this
participant group. And we'velearned a lot about sleep
health, about physical activity.
(07:59):
So the outputs from this workwill go on for decades ahead,
which is really exciting.
Rob Lott (08:07):
Do you have a sense of the current administration's
view on this project beyond justtheir sort of broad attempts at
quote, improving efficiency orreducing costs, are they paying
attention to the work of all ofus? And if so, what do you think
(08:28):
their take is?
Eric Topol (08:30):
I think it's a great question you're asking. And I'm
worried about that because ofeverything that's been going
against diversity and equity,which this whole program was
dedicated to trying to counterthe prior medical research. Josh
Denny, who is in charge of thewhole program at NIH, has doing
(08:53):
everything he can to work withCongress to preserve its support
to augment its support. Because,as you may remember, the
Framingham study done manydecades ago, was one of the most
important contributions ofmedicine ever. That was for
cardiovascular.
And it was again, also of onlyone ancestry, essentially. So
(09:16):
now we have an opportunity tochange the future. And if we
don't continue to support thisprogram, then I think just
because of it, emphasis ondiversity of all things, that
would be a tragedy. So I'mhoping that we will be able to
marshal new support now that theCures Act funding is basically
(09:39):
expiring. And it does takecommitment from Congress and
also not the attitude that we'reseeing with respect to the
administration to somehowdiscount the importance of multi
ancestry work.
What are
Rob Lott (09:55):
you most excited about with this project going forward?
What do you hope to see in thenext couple of years? Funding
aside, let's say it's a perfectworld and you have all the
funding you need. What would youlike to see happen in the next
few years?
Eric Topol (10:10):
Well, think it gets to the super agers book. And
that is a blueprint for how wecan prevent, or at least
markedly delay the three bigkillers, the three big age
related diseases, cancer,cardiovascular, and
neurodegenerative. Because inorder to do that, we have to
(10:31):
have all the layers of data foreach person, which is what all
of us is really geared for. Andonce you do, that's what's so
exciting now, is that you canuse AI, multimodal AI, to
integrate each person's billionsand billions of data points to
say you're vulnerable and highrisk for this particular
(10:52):
condition at this time. Used tobe we might say, Oh, your risk
is for let's say heart disease.
But we didn't know if you'reit'd be when you're 98, or when
you're 58. Now we can very,really fine tune this and say,
you know, when it is and what wecan do to prevent it. Because
the important thing to emphasizeis that three these three age
(11:15):
related conditions areincubating in us for over twenty
years. So we have a lot of timeto work with here. And if we
don't take advantage of that,then we're really being stupid.
Rob Lott (11:28):
I wanna hear more about, your experience
developing this book, in just amoment. But first, let's take a
quick break. And we're back. I'mhere with Doctor. Eric Topol,
(11:56):
Director of Scripps ResearchTranslational Institute and the
author of An Evidence BasedApproach to Longevity.
Doctor. Topol, who is theaudience for this book? Who were
you thinking about when youwrote it?
Eric Topol (12:11):
Everyone who'd like to expand their health span, or
extend it, that is. I think mostpeople would. We're not talking
about longevity really, eventhough that's in the title,
we're really talking abouthealth span, which is the number
of years with freedom from thebig three age related diseases.
Rob Lott (12:33):
Great. In your introduction, you described two
patients. And I'm wondering ifyou can describe them briefly
for our listeners here who maynot have gotten to read the book
yet, and explain how theirexperiences informed your
understanding of aging.
Eric Topol (12:51):
Yeah, so these are two patients of mine. Mrs. LR is
98 years old, and she's neverbeen sick with any of these
diseases. And she is noteworthybecause all of her relatives,
her parents, her siblings, alldied at young ages. So she's,
(13:13):
you know, the last one standingin her family, age 98, and
perfectly healthy.
So this is not only a genestory, in fact, that plays a
very minimal role for healthyaging, as we've learned from
her. And she is quite remarkablebecause she does oil painting
and has won awards. She's had agallery for her painting. She
(13:37):
does all these thousand puzzlepieces, assembles them. She
plays Remy Cube with seven otherwomen of similar age every week.
So she's not isolated sociallyas most people are more as we
get older. So she's a veryinteresting person to learn
from. The other patient has beenmine for a patient mine for over
(14:00):
thirty, thirty five years. He'snow 99. He's got another year
age in his book.
I just spoke to him thismorning, in fact, he's doing
exceedingly well. But unlike thefirst patient, he's had heart
disease since age 65. And he'sbasically a triumph of our
treatments for heart disease,and our ability to have
(14:22):
secondary prevention, you know,after bypass surgery, after
heart attacks. But in thefuture, we're gonna have people
like him who prevented theirheart disease totally. So
whereas he's 99 and his wife isplanning his one hundredth
birthday party, gave me a savethe date.
You know, we're going to see alot more of these two people in
(14:44):
the future if we use the datathat we have in our hands now
and more to come. It's going tochange the natural history and
the fulfilling the realexcitement of primary
prevention. That's been afantasy of ours in medicine. We
never really done it in anymeaningful way. But we have the
(15:04):
tools through this wholeindividualized medicine, data
rich world to accomplish it.
Rob Lott (15:10):
You've alluded to this earlier in our conversation, but
can you say a little more aboutwhat's kept us from fulfilling
that goal of primary prevention?Why is that so hard? And why are
we only now just starting tomove in that direction?
Eric Topol (15:24):
Well, lots of things here. First, as I mentioned,
we've learned now it takes atleast twenty years for those
three diseases to take root.Secondly, we know the mechanisms
of how these diseases progress,and they all have a common
thread. They rely on our immunesystem and inflammation. That is
(15:44):
the immune cells such aslymphocytes and neutrophils
secreting proteins that rev upinflammation in our body or in
our brain in the case ofneurodegenerative diseases.
And also, we've learned so muchabout how lifestyle factors can
help. So not just diet,precision details within the
(16:07):
diet, like ultra processedfoods, and the amount of protein
and all those sorts of things,exercise, fundamental, sleep
health, but then many otherlayers of data such as
environmental toxins likemicroplastics and air pollution,
and forever chemicals. Sobasically, we've learned all
(16:28):
these things and added is thething I mentioned with respect
to, we had only a fuzzy idea ofbeing able to say you're at risk
for this. And it was basicallyusing this polygenic risk score,
pretty primitive. And it didn'tsay when it just said you're at
some risk, and it wasn't veryaccurate.
But now we have amazinglyaccurate ways. We have a protein
(16:52):
marker, it's just one proteincalled p tau two seventeen, a
breakthrough, where we can sayyou are at high risk for
Alzheimer's, when, when you'regoing to have mild cognitive
impairment. And if you changethese things, predominantly
lifestyle factors, and possiblydrugs that we have even now to
(17:12):
repurpose, we're going to changethat whole thing and prevent you
from ever manifesting.Alzheimer's, well, that's a
dream. So there's beenremarkable progress, and most
people aren't in touch withthat.
I I recently wrote a a subjectin in ground truths about p tau
two seventeen, and I was stunnedin the poll of it. Thousands of
(17:34):
people, they'd never even heardof it. And, you know, a lot of
these people have family historyof Alzheimer's or have an APOE4
allele that they're worriedabout, you know, a gene test
they've had. So we have newtools now, based on all the
things I've been saying toaccomplish this very far
reaching objective that we'venever really done before.
Rob Lott (17:58):
The subtitle of your book is quote, an evidence based
approach to longevity. And asyou well know, there's a high
quality evidence and low qualityevidence and everything in
between. Of course, writing awork of non fiction is very
different from writing anacademic journal article, a meta
(18:23):
analysis, systematic review. Howdid you go about judging which
evidence to include and which toleave out when you were
developing this book?
Eric Topol (18:33):
You'll note I had over 1,800 citations in the
book. So it's much more like amedical type of report. But I
tried to, of course, translateit more for the public that has
less grounding in this kind ofwork with a caveat in the book
in the introduction, some ofit's kind of dense and just skip
over that you get to that pointwhere you'd say, I don't get
(18:57):
this. The point being is, Iobviously for in working in
medical research for forty yearsnow, I have a pretty good sense
of high quality by knowing theresearchers involved, the
journals where it's published,the quality of the work, you
know, how so much of it isrigorous, and basically tried to
(19:20):
use everything we have to makejudgments about, for example,
what are the lifestyle factorsthat we can say are hard
evidence? And where is where arethe soft spots?
But basically, your point is socritical, because there's so
much pseudoscience out there.There's all these people hawking
supplements, longevity clinics,longevity companies, I mean,
(19:43):
this is just riddled with allsorts of things with no
evidence, and selling andbasically predatory, okay? So
that was one of the reasons whyI thought there was a need for
the book. We have books outthere where people are saying,
get a total body MRI, starttaking rapamycin, and all these
(20:04):
other things, get all theseother tests, and there's no
data, no evidence. So what I'mtrying to do is set the record
straight as best as I possiblycan by everything we know.
And I'm also gratified thatsince the book was done and went
to the printer just a few weeksago, even more stuff has been
coming out to reinforce what Ithought where we were headed to
(20:28):
really anchor it. So I'm pleasedthat these major conclusions,
these blueprints are gonna beconsidered, I think by most
people quite accurate.
Rob Lott (20:40):
Great, well, you'll have to start that folder of
additional evidence for thesecond edition.
Eric Topol (20:46):
Keeping that active adding new things that if I ever
do that, or if I just hit on oneair at a time, because as you
say, every week, there'ssomething coming up to help us
in this way.
Rob Lott (21:01):
So a few months ago, Health Affairs published a paper
led by Doctor. Don Berwick,which was part of the National
Academy's Vital Directionsseries, offering an agenda for
the next administration. And inthat paper, one of the goals for
our healthcare system that theauthors proposed is quote, an
(21:24):
additional decade of healthybirthdays after retirement. And
I'm curious how you see that assort of in alignment or not with
your own thesis of this book,and really what steps our
nation's leadership should betaking potentially to fulfill
that goal. What role really dopolicymakers have when it comes
(21:48):
with a goal like longevity?
Eric Topol (21:50):
Yes, I mean, I think the world of Don Berwick, and I
think what that was getting atis that in the book, I also
summarize, we have data that ifpeople have their lifestyle
factors in optimum form, theycan get seven years more healthy
aging right now. The problem ismost people don't have the right
(22:14):
type of physical activity, theattention to sleep health, and
achieving that. And really, youknow, very healthy diets, you
know, this ability to get peopleto go to a healthy lifestyle, I
think will be much increasedwhen people know that it's
specific risk that is for sure.Timing, and know, it isn't like
(22:40):
most of us are going to get allthese three diseases. Most of us
are really vulnerable perhapsfor one.
And so if you start toindividualize, that's the whole
tenet of precision medicine, Andthen you'll have a much higher
rate of moving towards healthylifestyles, and eking out, you
know, what easily could be adecade of healthy aging. The
(23:01):
point is not to live an extraten years with dementia, or, you
know, as a cancer survivor, butwith all sorts of complications,
but to achieve primaryprevention of these conditions
so that you can live healthilyand you're not frail, you're not
compromised. That's what ourgoal has to be. The sad part is
(23:23):
we have an administration whopurports to say they want to
really bring down chronicdisease. But the actions don't
be speak that with dramaticreductions of support for the
public health agencies, NIH,FDA, CDC.
If we're gonna really do this,we actually have to increase our
(23:45):
support because this isn't gonnahappen by accident. We're not
gonna be able to do what we'retalking about today without
dedicated programs that arefunded to achieve these goals
and harness the opportunity,making it a national priority.
Rob Lott (24:00):
So longevity and superaging, these concepts are
often thought of as sort ofsuccess at forestalling death.
Now with your previous comment,I think I have a sense of how
you think about these goals. Butafter all, death is a scary
(24:21):
thing with all kinds of emotionsand anxiety at play. And it also
obviously has implications forsociety as a whole. Now famously
back in 2014, Ezekiel Emanuelwrote an article in The Atlantic
under, the title, quote, why Ihope to die at 75.
(24:45):
And in that, he wrote that,death is a loss. It deprives us
of experiences and milestones oftime spent with our spouse and
children. It deprives us of allthe things we value. But here is
a simple truth that many of usseem to resist, that living too
long is also a loss. I assumeyou read that article at the And
(25:09):
I'm curious how you thoughtabout it then.
And now as you've developed thisbook ten years later, how you
might respond.
Eric Topol (25:17):
Yeah, no, I know Zeke and I totally disagree with
him on this. And as I think heapproaches 75, he may wanna
write a retraction. I thinkbasically he takes this
fatalistic approach. And Ihappen to be an optimist. And
basically what I've thought is,there's gotta be a better way
(25:37):
than what we have now.
And I think we're seeing thatbetter way emerge. And yes, if
you have a very bad chronicdisease and you're debilitated,
well, maybe that's living,extending life, that's not the
goal. But what we need to do iswell beyond age 75, we're
(25:59):
talking about the two patientsthat I present in the book and
come back to it many times, aged98 and 99, we're gonna see a lot
more of that. We can do this. Sorather than a defeatist
attitude, I see us get promotehealthy aging because right now
people age 65, they have threechronic diseases on average.
(26:21):
That's not what that's not thekind of population that is gonna
be the answer to this. We needto prevent preempt these
diseases. And we could start,you know, at age 30 and 40 now
we have the means to do that.
Rob Lott (26:34):
So people have been pursuing longevity for
centuries, you know, fountain ofyouth, it goes all the way back.
And, of course, with time, we'veseen incredible advances in our
knowledge and the technologyavailable to act on that
knowledge. I'm curious if youcould say just a little bit
(26:54):
about this moment and why you'republishing this book now. Is it
just that now is the latest stepin the march of time forward and
progress? Or do you see this assort of a hinge point in history
when it comes to science andhealth?
Eric Topol (27:14):
Okay, so the science of aging has advanced and it's
remarkable. And the thing that alot of people are thinking about
in the science of aging is wecould reverse aging. We could
reprogram cells. We could givethese synolytic drugs that get
rid of senescent cells in ourbody. We could prolong lengthen
(27:36):
our telomeres, or you take NADplus supplements or rapamycin or
a long list, right?
The problem, each of thosecarries significant hazard. And
what I'm trying to do is say,wait a minute, one of those
might work someday to slow bodywide aging, But let's not
(27:56):
overlook the science of aginghas brought us clocks. We never
had clocks before. Okay, we havebody wide aging clocks,
methylation epigenetic clocks,we've got organ clocks, these
protein organ clocks. We canclock our immune system.
We have these proteins, like Imentioned, we have ability to
(28:18):
pick up tumor DNA in our plasmaat the microscopic level where
well before any scan would seeit. So we have now these new
ways to be on top of our agingprocess. That's to me, the real
excitement about the science ofaging. And it's the book is
(28:40):
really intended to bring thatout, to really highlight these
exciting advances in contrast tothe hype about all these things
and this, you know, the hawkingof supplements and the predatory
stuff, which is baseless. Itdoesn't have the evidence in
people.
It's all about rodents, youknow? And so if you can
(29:01):
reprogram a mouse and make anold mouse into a young mouse,
that's great. But it just sohappens you also create tumors
in the mouse. So, you know,these are elegant science
approaches, but the science ofaging has brought us something
else which we can capitalize on.And the reason that's important
is you can use these clocks tosee if you're making headway in
(29:26):
any given individual, right?
So if you have a brain organclock, and it says that you are
65 years old, even though you'rereally 55 years old, you know,
that's serious. That's aproblem. We then go on to
changing your lifestyle and allsorts of things. And by then all
of a sudden, brain organ clockis 45. Well, okay, that's the
(29:51):
science of aging at work.
And so we can do this and it'sexciting. And it applies to each
of the three major diseases tostay ahead of them, get ahead of
them. The earlier we start inlife, the better, but there's
never a time when it's too late.
Rob Lott (30:06):
Well, that's such an encouraging note. Before we wrap
up, I'm curious if there are anyother major themes you want to
make sure that our listenerstake away from the work you've
done on this book?
Eric Topol (30:19):
Well, the interaction of our lifestyle
factors with the ability toprevent these diseases is really
quite extraordinary. And it'snot just these headings of diet
and sleep and exercise, But thedetails, you know, like ultra
processed food, how muchprotein, caffeine, alcohol, I
(30:40):
mean, there's a lot of myths andmiscues out there. So I try to
set all that straight, but alsoget into the layers of lifestyle
that people haven't previouslyconsidered lifestyle. I call it
lifestyle plus. And that's theseenvironmental toxins, air
pollution, and microplastics andforever chemicals, and the
(31:03):
importance of things like socialisolation, time in nature, and
many other things.
So the lifestyle factors is thebiggest chapter in the book,
Because if we really takecontrol of those, both the
things that are doing good, andthose that are being harmful,
that's a real important pathtowards healthy aging.
Rob Lott (31:24):
Great. Well, with that, I'm gonna go for a walk in
the woods. I hope that couldhelp along the way. Doctor. Eric
Topol, thank you so much fortaking the time to speak with us
today.
Eric Topol (31:35):
Thank you.
Rob Lott (31:36):
And to our listeners, please tune in again next week.
If you enjoyed this episode,recommend it to a friend, smash
the subscribe button and tune innext week. Thanks for listening.
If you enjoyed today's episode,I hope you'll tell a friend
(31:57):
about a health policy.
Hello, and welcome to A Health I'm your host, Rob
Lott. Friends, it's another oneof our very special episodes. As
you know, typically on a healthodyssey, we feature the authors
of recent health affairsarticles to dig in on their
(00:54):
research and explore theirfindings. But about once a
month, our producer Jeff lets uspush the boundaries a bit to
bring on a special guest fromsomewhere perhaps a little more
exotic in the health policyuniverse to talk about their
experiences in the field and toreflect on their own
(01:14):
understanding of this verystrange moment in time. Today,
we're so lucky to be here withthe one and only Doctor.
Eric Topol, Director and Founderof the Scripps Research
Translational Institute. Doctor.Topol is one of the leading
voices for reason, transparency,and optimism as driving forces
(01:37):
of the biomedical enterprise. Heis a principal investigator of
the All of Us Research Program,a huge precision medicine
initiative created by Congressand funded by the NIH. He's a
practicing cardiologist, andwith all of his free time, the
author of three bestsellingworks of nonfiction about
(02:00):
health, medicine, andtechnology.
Now his fourth book publishedjust this month is titled An
Evidence Based Approach toLongevity. Doctor. Eric Topol,
welcome to A Health Odyssey.
Eric Topol (02:15):
Thanks so much. It's great to be with you.
Rob Lott (02:17):
So in a moment, we'll discuss the new book. But first,
you've authored a number ofbooks on precision medicine, AI,
the bleeding edges of thesetechnologies. Can you tell us a
little bit about your journeyfrom aspiring doctor to sort of
leading voice on some of thesereally cutting edge issues?
Eric Topol (02:40):
Well, thank you. I mean, I think the thing for me
is always to try to take atleast my best shot for where are
we headed in medicine. And we'rein some ways going back to
college, I mean, genetics, weweren't quite ready until we
could sequence the genome. Butthat's what led in the 1990s,
(03:01):
when I was at Cleveland Clinicto set up the first
cardiovascular biobank, whereover 10,000 people back then,
where we had their gene assaysfor what got them into the
cardiovascular world of healthissues. And so basically, what
(03:22):
happened was in sequence, I gotinto genetics again, and then
sensors because that was, it'snot just the genes, there's a
lot more to us than that.
And then this whole theme ofindividualized medicine, where
the more layers of data on eachof us, the better we're going to
do in terms of ultimatelypreventing diseases. That's what
(03:44):
the new book is about. But it'sbasically been a very, for me, a
logical building up of firstdigitizing human beings with
these things we're just talkingabout, then democratizing,
because once you have everythingdigitized, doctors are no longer
in control of everything, whichis good. And then the book Deep
(04:07):
Medicine, that was the last bookI wrote was about AI and how
that ultimately with new modelsthat we needed and we have now
is going to be transformative.So we've got the AI models and
now what are we going to do?
And that's kind of, I thinkwhere the excitement lies for me
and hopefully the medicalcommunity and patients as well.
Rob Lott (04:30):
So I think one place where all of these different
trends come together is the Allof Us Research Program, which
was created as part of thetwenty first Century Cures Act,
which believe it or not was nineyears ago. And generally,
(04:52):
correct me if I'm wrong here,the idea is to collect genetic
and health data for upwards of amillion participants with the
goal of opening the door topotentially new innovations in
precision medicine, movingbeyond sort of one size fits all
approach to clinical trials andthe findings of clinical
(05:13):
research. Enrollment started in2017. And here we are a number
of years later, a full blownpandemic later. Where do things
stand?
What have you seen change? Whathave you learned in the last few
years from that project?
Eric Topol (05:30):
Yeah, it's been, I think the biggest commitment for
a singular or single project inthe history of American medical
research billions of dollars.Its real origin was
interestingly with then SenatorObama, who pressed for something
like this, and then FrancisCollins, the NIH director. So it
(05:50):
got off the ground just as yousaid, and now has over 850,000
very diverse participants. Abouthalf are not European ancestry.
So it's very different than theUK Biobank or other biobanks
around the world.
But what's noteworthy is themajority have had whole genome
(06:13):
sequencing and progressivelythey're getting their data. So
that is one layer of data. We'vealso had sensors in a large
proportion. And the intent isgoing forward, we'll have many
other layers of data to helpguide these participants to get
(06:34):
better health care. The onlyproblem is our funding has
gotten substantially reduced.
The Cures Act, the Congress andwhatnot, and our current cuts.
So it may not be as quiteambitious as originally laid
out. But at least it's a verylarge population, uniquely
(06:55):
diverse, that has rich data, andit's being made to the entire
world of medical researchers. Sojust like the UK Biobank, a lot
of good things will come from itand already have.
Rob Lott (07:07):
Well, that's a great segue. Can you maybe give us an
example or two of somethingexciting or promising that's
come out of this projectalready?
Eric Topol (07:17):
Well, we've already learned of some new gene
variants that account for someof the most important age
related diseases, includingcancer and cardiovascular or
neurodegenerative. And that wascritical because previous to the
all of us, so many of thestudies for genetics were in
(07:38):
predominantly white and Europeanancestry. So this multi ancestry
capability made a hugedifference. But the, for
example, we distributed Fitbitsvery widely throughout this
participant group. And we'velearned a lot about sleep
health, about physical activity.
(07:59):
So the outputs from this workwill go on for decades ahead,
which is really exciting.
Rob Lott (08:07):
Do you have a sense of the current administration's
view on this project beyond justtheir sort of broad attempts at
quote, improving efficiency orreducing costs, are they paying
attention to the work of all ofus? And if so, what do you think
(08:28):
their take is?
Eric Topol (08:30):
I think it's a great question you're asking. And I'm
worried about that because ofeverything that's been going
against diversity and equity,which this whole program was
dedicated to trying to counterthe prior medical research. Josh
Denny, who is in charge of thewhole program at NIH, has doing
(08:53):
everything he can to work withCongress to preserve its support
to augment its support. Because,as you may remember, the
Framingham study done manydecades ago, was one of the most
important contributions ofmedicine ever. That was for
cardiovascular.
And it was again, also of onlyone ancestry, essentially. So
(09:16):
now we have an opportunity tochange the future. And if we
don't continue to support thisprogram, then I think just
because of it, emphasis ondiversity of all things, that
would be a tragedy. So I'mhoping that we will be able to
marshal new support now that theCures Act funding is basically
(09:39):
expiring. And it does takecommitment from Congress and
also not the attitude that we'reseeing with respect to the
administration to somehowdiscount the importance of multi
ancestry work.
What are
Rob Lott (09:55):
you most excited about with this project going forward?
What do you hope to see in thenext couple of years? Funding
aside, let's say it's a perfectworld and you have all the
funding you need. What would youlike to see happen in the next
few years?
Eric Topol (10:10):
Well, think it gets to the super agers book. And
that is a blueprint for how wecan prevent, or at least
markedly delay the three bigkillers, the three big age
related diseases, cancer,cardiovascular, and
neurodegenerative. Because inorder to do that, we have to
(10:31):
have all the layers of data foreach person, which is what all
of us is really geared for. Andonce you do, that's what's so
exciting now, is that you canuse AI, multimodal AI, to
integrate each person's billionsand billions of data points to
say you're vulnerable and highrisk for this particular
(10:52):
condition at this time. Used tobe we might say, Oh, your risk
is for let's say heart disease.
But we didn't know if you'reit'd be when you're 98, or when
you're 58. Now we can very,really fine tune this and say,
you know, when it is and what wecan do to prevent it. Because
the important thing to emphasizeis that three these three age
(11:15):
related conditions areincubating in us for over twenty
years. So we have a lot of timeto work with here. And if we
don't take advantage of that,then we're really being stupid.
Rob Lott (11:28):
I wanna hear more about, your experience
developing this book, in just amoment. But first, let's take a
quick break. And we're back. I'mhere with Doctor. Eric Topol,
(11:56):
Director of Scripps ResearchTranslational Institute and the
author of An Evidence BasedApproach to Longevity.
Doctor. Topol, who is theaudience for this book? Who were
you thinking about when youwrote it?
Eric Topol (12:11):
Everyone who'd like to expand their health span, or
extend it, that is. I think mostpeople would. We're not talking
about longevity really, eventhough that's in the title,
we're really talking abouthealth span, which is the number
of years with freedom from thebig three age related diseases.
Rob Lott (12:33):
Great. In your introduction, you described two
patients. And I'm wondering ifyou can describe them briefly
for our listeners here who maynot have gotten to read the book
yet, and explain how theirexperiences informed your
understanding of aging.
Eric Topol (12:51):
Yeah, so these are two patients of mine. Mrs. LR is
98 years old, and she's neverbeen sick with any of these
diseases. And she is noteworthybecause all of her relatives,
her parents, her siblings, alldied at young ages. So she's,
(13:13):
you know, the last one standingin her family, age 98, and
perfectly healthy.
So this is not only a genestory, in fact, that plays a
very minimal role for healthyaging, as we've learned from
her. And she is quite remarkablebecause she does oil painting
and has won awards. She's had agallery for her painting. She
(13:37):
does all these thousand puzzlepieces, assembles them. She
plays Remy Cube with seven otherwomen of similar age every week.
So she's not isolated sociallyas most people are more as we
get older. So she's a veryinteresting person to learn
from. The other patient has beenmine for a patient mine for over
(14:00):
thirty, thirty five years. He'snow 99. He's got another year
age in his book.
I just spoke to him thismorning, in fact, he's doing
exceedingly well. But unlike thefirst patient, he's had heart
disease since age 65. And he'sbasically a triumph of our
treatments for heart disease,and our ability to have
(14:22):
secondary prevention, you know,after bypass surgery, after
heart attacks. But in thefuture, we're gonna have people
like him who prevented theirheart disease totally. So
whereas he's 99 and his wife isplanning his one hundredth
birthday party, gave me a savethe date.
You know, we're going to see alot more of these two people in
(14:44):
the future if we use the datathat we have in our hands now
and more to come. It's going tochange the natural history and
the fulfilling the realexcitement of primary
prevention. That's been afantasy of ours in medicine. We
never really done it in anymeaningful way. But we have the
(15:04):
tools through this wholeindividualized medicine, data
rich world to accomplish it.
Rob Lott (15:10):
You've alluded to this earlier in our conversation, but
can you say a little more aboutwhat's kept us from fulfilling
that goal of primary prevention?Why is that so hard? And why are
we only now just starting tomove in that direction?
Eric Topol (15:24):
Well, lots of things here. First, as I mentioned,
we've learned now it takes atleast twenty years for those
three diseases to take root.Secondly, we know the mechanisms
of how these diseases progress,and they all have a common
thread. They rely on our immunesystem and inflammation. That is
(15:44):
the immune cells such aslymphocytes and neutrophils
secreting proteins that rev upinflammation in our body or in
our brain in the case ofneurodegenerative diseases.
And also, we've learned so muchabout how lifestyle factors can
help. So not just diet,precision details within the
(16:07):
diet, like ultra processedfoods, and the amount of protein
and all those sorts of things,exercise, fundamental, sleep
health, but then many otherlayers of data such as
environmental toxins likemicroplastics and air pollution,
and forever chemicals. Sobasically, we've learned all
(16:28):
these things and added is thething I mentioned with respect
to, we had only a fuzzy idea ofbeing able to say you're at risk
for this. And it was basicallyusing this polygenic risk score,
pretty primitive. And it didn'tsay when it just said you're at
some risk, and it wasn't veryaccurate.
But now we have amazinglyaccurate ways. We have a protein
(16:52):
marker, it's just one proteincalled p tau two seventeen, a
breakthrough, where we can sayyou are at high risk for
Alzheimer's, when, when you'regoing to have mild cognitive
impairment. And if you changethese things, predominantly
lifestyle factors, and possiblydrugs that we have even now to
(17:12):
repurpose, we're going to changethat whole thing and prevent you
from ever manifesting.Alzheimer's, well, that's a
dream. So there's beenremarkable progress, and most
people aren't in touch withthat.
I I recently wrote a a subjectin in ground truths about p tau
two seventeen, and I was stunnedin the poll of it. Thousands of
(17:34):
people, they'd never even heardof it. And, you know, a lot of
these people have family historyof Alzheimer's or have an APOE4
allele that they're worriedabout, you know, a gene test
they've had. So we have newtools now, based on all the
things I've been saying toaccomplish this very far
reaching objective that we'venever really done before.
Rob Lott (17:58):
The subtitle of your book is quote, an evidence based
approach to longevity. And asyou well know, there's a high
quality evidence and low qualityevidence and everything in
between. Of course, writing awork of non fiction is very
different from writing anacademic journal article, a meta
(18:23):
analysis, systematic review. Howdid you go about judging which
evidence to include and which toleave out when you were
developing this book?
Eric Topol (18:33):
You'll note I had over 1,800 citations in the
book. So it's much more like amedical type of report. But I
tried to, of course, translateit more for the public that has
less grounding in this kind ofwork with a caveat in the book
in the introduction, some ofit's kind of dense and just skip
over that you get to that pointwhere you'd say, I don't get
(18:57):
this. The point being is, Iobviously for in working in
medical research for forty yearsnow, I have a pretty good sense
of high quality by knowing theresearchers involved, the
journals where it's published,the quality of the work, you
know, how so much of it isrigorous, and basically tried to
(19:20):
use everything we have to makejudgments about, for example,
what are the lifestyle factorsthat we can say are hard
evidence? And where is where arethe soft spots?
But basically, your point is socritical, because there's so
much pseudoscience out there.There's all these people hawking
supplements, longevity clinics,longevity companies, I mean,
(19:43):
this is just riddled with allsorts of things with no
evidence, and selling andbasically predatory, okay? So
that was one of the reasons whyI thought there was a need for
the book. We have books outthere where people are saying,
get a total body MRI, starttaking rapamycin, and all these
(20:04):
other things, get all theseother tests, and there's no
data, no evidence. So what I'mtrying to do is set the record
straight as best as I possiblycan by everything we know.
And I'm also gratified thatsince the book was done and went
to the printer just a few weeksago, even more stuff has been
coming out to reinforce what Ithought where we were headed to
(20:28):
really anchor it. So I'm pleasedthat these major conclusions,
these blueprints are gonna beconsidered, I think by most
people quite accurate.
Rob Lott (20:40):
Great, well, you'll have to start that folder of
additional evidence for thesecond edition.
Eric Topol (20:46):
Keeping that active adding new things that if I ever
do that, or if I just hit on oneair at a time, because as you
say, every week, there'ssomething coming up to help us
in this way.
Rob Lott (21:01):
So a few months ago, Health Affairs published a paper
led by Doctor. Don Berwick,which was part of the National
Academy's Vital Directionsseries, offering an agenda for
the next administration. And inthat paper, one of the goals for
our healthcare system that theauthors proposed is quote, an
(21:24):
additional decade of healthybirthdays after retirement. And
I'm curious how you see that assort of in alignment or not with
your own thesis of this book,and really what steps our
nation's leadership should betaking potentially to fulfill
that goal. What role really dopolicymakers have when it comes
(21:48):
with a goal like longevity?
Eric Topol (21:50):
Yes, I mean, I think the world of Don Berwick, and I
think what that was getting atis that in the book, I also
summarize, we have data that ifpeople have their lifestyle
factors in optimum form, theycan get seven years more healthy
aging right now. The problem ismost people don't have the right
(22:14):
type of physical activity, theattention to sleep health, and
achieving that. And really, youknow, very healthy diets, you
know, this ability to get peopleto go to a healthy lifestyle, I
think will be much increasedwhen people know that it's
specific risk that is for sure.Timing, and know, it isn't like
(22:40):
most of us are going to get allthese three diseases. Most of us
are really vulnerable perhapsfor one.
And so if you start toindividualize, that's the whole
tenet of precision medicine, Andthen you'll have a much higher
rate of moving towards healthylifestyles, and eking out, you
know, what easily could be adecade of healthy aging. The
(23:01):
point is not to live an extraten years with dementia, or, you
know, as a cancer survivor, butwith all sorts of complications,
but to achieve primaryprevention of these conditions
so that you can live healthilyand you're not frail, you're not
compromised. That's what ourgoal has to be. The sad part is
(23:23):
we have an administration whopurports to say they want to
really bring down chronicdisease. But the actions don't
be speak that with dramaticreductions of support for the
public health agencies, NIH,FDA, CDC.
If we're gonna really do this,we actually have to increase our
(23:45):
support because this isn't gonnahappen by accident. We're not
gonna be able to do what we'retalking about today without
dedicated programs that arefunded to achieve these goals
and harness the opportunity,making it a national priority.
Rob Lott (24:00):
So longevity and superaging, these concepts are
often thought of as sort ofsuccess at forestalling death.
Now with your previous comment,I think I have a sense of how
you think about these goals. Butafter all, death is a scary
(24:21):
thing with all kinds of emotionsand anxiety at play. And it also
obviously has implications forsociety as a whole. Now famously
back in 2014, Ezekiel Emanuelwrote an article in The Atlantic
under, the title, quote, why Ihope to die at 75.
(24:45):
And in that, he wrote that,death is a loss. It deprives us
of experiences and milestones oftime spent with our spouse and
children. It deprives us of allthe things we value. But here is
a simple truth that many of usseem to resist, that living too
long is also a loss. I assumeyou read that article at the And
(25:09):
I'm curious how you thoughtabout it then.
And now as you've developed thisbook ten years later, how you
might respond.
Eric Topol (25:17):
Yeah, no, I know Zeke and I totally disagree with
him on this. And as I think heapproaches 75, he may wanna
write a retraction. I thinkbasically he takes this
fatalistic approach. And Ihappen to be an optimist. And
basically what I've thought is,there's gotta be a better way
(25:37):
than what we have now.
And I think we're seeing thatbetter way emerge. And yes, if
you have a very bad chronicdisease and you're debilitated,
well, maybe that's living,extending life, that's not the
goal. But what we need to do iswell beyond age 75, we're
(25:59):
talking about the two patientsthat I present in the book and
come back to it many times, aged98 and 99, we're gonna see a lot
more of that. We can do this. Sorather than a defeatist
attitude, I see us get promotehealthy aging because right now
people age 65, they have threechronic diseases on average.
(26:21):
That's not what that's not thekind of population that is gonna
be the answer to this. We needto prevent preempt these
diseases. And we could start,you know, at age 30 and 40 now
we have the means to do that.
Rob Lott (26:34):
So people have been pursuing longevity for
centuries, you know, fountain ofyouth, it goes all the way back.
And, of course, with time, we'veseen incredible advances in our
knowledge and the technologyavailable to act on that
knowledge. I'm curious if youcould say just a little bit
(26:54):
about this moment and why you'republishing this book now. Is it
just that now is the latest stepin the march of time forward and
progress? Or do you see this assort of a hinge point in history
when it comes to science andhealth?
Eric Topol (27:14):
Okay, so the science of aging has advanced and it's
remarkable. And the thing that alot of people are thinking about
in the science of aging is wecould reverse aging. We could
reprogram cells. We could givethese synolytic drugs that get
rid of senescent cells in ourbody. We could prolong lengthen
(27:36):
our telomeres, or you take NADplus supplements or rapamycin or
a long list, right?
The problem, each of thosecarries significant hazard. And
what I'm trying to do is say,wait a minute, one of those
might work someday to slow bodywide aging, But let's not
(27:56):
overlook the science of aginghas brought us clocks. We never
had clocks before. Okay, we havebody wide aging clocks,
methylation epigenetic clocks,we've got organ clocks, these
protein organ clocks. We canclock our immune system.
We have these proteins, like Imentioned, we have ability to
(28:18):
pick up tumor DNA in our plasmaat the microscopic level where
well before any scan would seeit. So we have now these new
ways to be on top of our agingprocess. That's to me, the real
excitement about the science ofaging. And it's the book is
(28:40):
really intended to bring thatout, to really highlight these
exciting advances in contrast tothe hype about all these things
and this, you know, the hawkingof supplements and the predatory
stuff, which is baseless. Itdoesn't have the evidence in
people.
It's all about rodents, youknow? And so if you can
(29:01):
reprogram a mouse and make anold mouse into a young mouse,
that's great. But it just sohappens you also create tumors
in the mouse. So, you know,these are elegant science
approaches, but the science ofaging has brought us something
else which we can capitalize on.And the reason that's important
is you can use these clocks tosee if you're making headway in
(29:26):
any given individual, right?
So if you have a brain organclock, and it says that you are
65 years old, even though you'rereally 55 years old, you know,
that's serious. That's aproblem. We then go on to
changing your lifestyle and allsorts of things. And by then all
of a sudden, brain organ clockis 45. Well, okay, that's the
(29:51):
science of aging at work.
And so we can do this and it'sexciting. And it applies to each
of the three major diseases tostay ahead of them, get ahead of
them. The earlier we start inlife, the better, but there's
never a time when it's too late.
Rob Lott (30:06):
Well, that's such an encouraging note. Before we wrap
up, I'm curious if there are anyother major themes you want to
make sure that our listenerstake away from the work you've
done on this book?
Eric Topol (30:19):
Well, the interaction of our lifestyle
factors with the ability toprevent these diseases is really
quite extraordinary. And it'snot just these headings of diet
and sleep and exercise, But thedetails, you know, like ultra
processed food, how muchprotein, caffeine, alcohol, I
(30:40):
mean, there's a lot of myths andmiscues out there. So I try to
set all that straight, but alsoget into the layers of lifestyle
that people haven't previouslyconsidered lifestyle. I call it
lifestyle plus. And that's theseenvironmental toxins, air
pollution, and microplastics andforever chemicals, and the
(31:03):
importance of things like socialisolation, time in nature, and
many other things.
So the lifestyle factors is thebiggest chapter in the book,
Because if we really takecontrol of those, both the
things that are doing good, andthose that are being harmful,
that's a real important pathtowards healthy aging.
Rob Lott (31:24):
Great. Well, with that, I'm gonna go for a walk in
the woods. I hope that couldhelp along the way. Doctor. Eric
Topol, thank you so much fortaking the time to speak with us
today.
Eric Topol (31:35):
Thank you.
Rob Lott (31:36):
And to our listeners, please tune in again next week.
If you enjoyed this episode,recommend it to a friend, smash
the subscribe button and tune innext week. Thanks for listening.
If you enjoyed today's episode,I hope you'll tell a friend
(31:57):
about a health policy.
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