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Language: en
many people believe that humans are born
to die and that even if we could extend
human life we shouldn't I hate that idea
and believe that thanks to AI we are on
the brink of a biotech Revolution that
will radically extend human life to help
us explore this Frontier I bring you
today's guest a scientist and
entrepreneur who believes that at a
minimum AI is going to dramatically
alter Health span and that will have
thrilling consequences as long as we
don't mess it up that in mind I bring
you Dr mmud Khan
given the fact that most men lead lives
of quiet desperation why should anybody
care about extending their
life well let's uh let's think about it
from a society point of view and an
individual point of view
okay from a society
perspective if we can keep the majority
of people functional and health and I'm
going to distinguish between what we
think about as healthy versus
independently function
active contributors to society and their
family and their loved ones if we can do
that Society should care the GDP impact
as calculated by Andrew Scott a
professor at London Business School and
Oxford University in England and others
whove verified this data have shown that
the impact in the US in terms of GDP is
around1 to4 trillion dollar of GDP
impact just for a 12month extension of
healthy life not maximum life but but
just keeping us healthy so Society
absolutely should care Medicare UK NHS
any of these organizations cannot
currently afford the health care cost of
just providing Health Care to people as
they age it's not possible today we
haven't figured out the solution well
the Sol the alternative is just keep
people healthy they have not only less
need for chronic care but they continue
to contribute now at an individual level
most people I talk to and there lots of
surveys done people want to remain
independent active and health not
defined by a 20-year-old if you have
somebody 20 what is healthy and you ask
somebody who's 40 or 60 what they mean
by healthy most 60-year-olds will say
hey can I continue to be active can I
have the mental capacity and physical
capacity to be independent and can I
contribute professionally or personally
in a meaningful way that's one aspect of
what is being quote a healthy lifestyle
right most people care that's what they
want people don't want to live longer if
you ask them the question do you want to
live as long as possible and in their
mind that's 30 years spent in a nursing
home nobody that I know wants that very
important distinction no doubt now I
look at the moment that we're in right
now as an incredibly disruptive moment
there certainly as somebody that lives
in the US you can feel the tension
rationing up you can feel the sense of
divide and when you look at what things
exacerbate that anything that is going
to negatively impact the economy is just
going to put you in a really precarious
position when we look at what's going on
in terms of government spending and the
the pyramid that's about to flip upside
down where we go from most people are
young to most people are old and there
are fewer young people to take care of
them when I look at the problem
currently of an aging population where
Health SP is not taken into
consideration and it's just lifespan and
now we're spending just gobs of money on
supporting people from a healthc care
perspective um are we doomed if we don't
Rectify this situation and get those
health care costs under
control well I wouldn't use the word
doomed however I would ask ourselves
what are the options we
have those are challeng if we do you
know no action is a decision and if we
don't take any action in business as
usual we've seen what's happened the
last 20 30 years exactly as you point
there are economic challenges now
there's labor shortages on top of that
and developed countries where the birth
rate has dramatically
Fallen the life expectancy over the last
60 70 years has been extended by at
least 30 years let's say 20 years of
that is requiring sign significant
resources from a healthare system given
that burden societies are asking
ourselves what can we do and you know it
is itself divisive because if you're a
young person in a payforward society and
developed countries are a payforward
society by the way so are developing
country just it's not structured and so
in a in a payforward society I'm a young
person working today I'm supposed to be
paying taxes so I can take care of the
last Generation Well if there's a few of
those as you point out in that pyramid
that's it's okay that's part of being
but all of a sudden if you're in China
and you're one grandchild with four
grandparents how am I supposed to
contribute to that economic model let
alone personally having to take care of
that's divisive right how am I supposed
to do that so what are the
Alternatives it's going to have to be
Innovation Innovation across the
Spectrum which means everything from
policies of how we think about our
taking care of society
down to technological breakthroughs and
I don't mean just biology the whole
spectrum of technology to allow leverage
of the fewer and fewer young people we
have as well as the ability to use fewer
people to generate more and more
activity both financially but also
Services right that's true leverage and
industrialization over the last 100
years has allowed humans to create huge
leverage in every aspect of Our Lives
what we have to ask ourselves now is
what is that next scurve of that
leverage right how can technology help
us what are the policies that will
enable that what's the financial
policies that will do that what are
societal Norms how do we how do we
enable all of this and there there's
multiple aspects of this uh not just
biology and which means something that
you do for a living we need to start
talking to people in the terms that they
understand and one of the biggest gaps
and I've been in science 40 years is
scientists can't be on their own telling
this story scientists are not good at
telling the story and what we learned in
covid is what was being said as an
expert was not what was being heard in
some cases it divided us so I would say
part of the challenge that we have to
overcome is we got to figure out how to
get people on the same page to
understand what the challenge is but
importantly also based on clear evidence
point out the opportunity and the
opportunity is huge everybody benefits
one other thing about
divisive what we have to think about is
the Haves and the Have Nots not just
within a society but across the world
every human being is aging but imagine a
world where you have technological
breakthrough which allows a population
and individuals to remain healthy longer
more productive more able to contribute
to their society all great but if the
only civilians and society that can do
that are rich countries then that
economic divide between the rich and the
poor countries will continue to widen if
that happens we're going to have
increase this challenge of Haves and
Have Nots so it's very important that we
ask ourselves another question on the
assumption that we can have
technological progress and I'm pretty
confident that will happen how do we
democratize it how do we make sure that
the masses are impacted in a way that
whether you are less well off within the
United States or are financially more
capable you have access to this the only
way to do that is democratization of
Technology we used to think that some
ubiquitous dream but cell phones told us
and showed us that very expensive
technology can become ubiquitous it it
really it requires
not just technological breakthrough but
Innovation and business models and it
was Innovation and business models that
democratized cell phone technology the
poor Rickshaw driver in a Asian country
has a cell phone we would not have
imagined that possible even 20 years
ago so you talk about the opportunity
being massive what is the opportunity
exactly just extending the healthy life
expectancy so let let's take a look at
we Define retirement age let's say 60 or
65 you know this was defined as I'm sure
you know after around World War II by
European countries and the number was
picked because most people didn't live
past 60 so it a great model right well
I'm going to give I'm going to guarantee
you a government pension if you last
live past 60 well if 90% of the
population didn't do that I didn't have
to take on responsibility so guess what
70 years later our definition of
retirement age in most countries is
still 60 or 65 we're assuming that after
that age you're no longer contributing
in a meaningful way and you become a net
recipient well the first thing that that
raises
is as soon as you turn 65 are you are
you now no longer contributing I would
say people are churches Charities if you
look at informal contribution to the GDP
in the United States in Europe and the
UK and many Asian countries older people
continue to serve next Generations in
countries with more formal employment
why should there be in particular when
knowledge workers are actually in high
demand because there's fewer of them so
these are the sort of links that we have
to think about and say what is it we're
extending right we're
extending
Health throughout your life allowing you
to contribute through all stages of your
life then it comes down to choices I'm
not saying everybody should be working
till they're 80 because they don't have
a choice but we we can choose to
contribute and everybody has a chance to
contribute in different ways whether
it's taking care of your grandparents
sorry grandchildren taking providing
support to your local church your local
charity volunteering at the local
hospital or continuing to work as an
executive new careers you and I have had
more than one
career why should it be one career or
two careers or three careers why can't
it be four
careers now is society set up for that
are we as Employer set up for that I'm
going to be provocative what's the
mission of an educational institute if
it only serves you and your life until
you're
22 is that the only mission of an
educational institute maybe we have to
ask us University presidents that their
role in a society is far more than
taking teenagers and giving them college
degrees give me an example what would
you want them to
do why couldn't an engineer who was
trained in the 70s and 80s be now
retrained as a data scientist and an AI
because they won't want to be hearing so
this is my my big concern and I'm going
to I'm going to pull a dark cloud over
us for a second I by Nature I am
optimistic but reality is constantly
trying to convince me that I should be
way more
pessimistic and you said societal norms
and I think that may be the thing that
we most have to think about and when
when I think about okay people been
raised thinking that they're going to
get to retire at 65 that they can then
put their hand out they have an
expectation that somebody's going to
look after
them that like you said works when
you've got a ton of people under you and
most people have died by then you're one
of the lucky few that's alive it does
not work when you're super topheavy and
that is a position that we're running
towards and I feel like everybody has a
sort of generic sense of either AI is
going to save us robots are going to
save us uh magically we I mean coming
from a US perspective we'll be able to
print our way out of it and just give
print money uh and be able to give money
away and everything's going to be great
and the reality is I think that people
are going to have to fundamentally shift
their perspective but historically
especially when debt gets involved the
only time that people shift their
perspective is when there is literal
Bloodshed and so I find that deeply
distressing and so when I think about
how do we how do we migrate people to
the real opportunity where so I am
very hopeful that not only can we extend
health span but we can extend lifespan I
don't want to I don't want to believe uh
that we're stuck at 120 I know we don't
have evidence yet so I won't I won't
back you into the corner of of uh
telling me that it is possible
but all of that is such a radical
transformation that even if we just
isolate it to the pyramid is going to
flip we are demographics they're set
there's no way to suddenly have a lot
more young people you can have a lot
more infants but you can't have a lot
more 20-y olds takes 20 years to get
there so we the pyramid is going to flip
and now the question is how do we flip
that pyramid well and I think if we
don't change cital norms and expect
people to live and work longer and
contribute more meaningfully to
basically their own caretaking their own
health care uh contributing to GDP all
of that if if we don't figure out a way
to psych locally get people on board
with that we are going to have a real a
a catastrophe that I have not mapped out
yet to figure out exactly what that
catastrophe looks like because you have
very angry old people in fact now that I
say this out loud the the problem you
will run into is they will continue to
wield political force and now you will
get you were referring earlier to what's
known as the J coefficient for people
that have never heard that word before
where you get a massive divide between
rich and poor right
I'm going to guess though I've not heard
of it that there's an equal
psychological principle that is
political power and if you have the old
generation wielding all the political
power you will get an uprising of young
people who just won't tolerate
it help me see a way out of this so most
of what you said were in full alignment
and agreement it's interesting because
everything you just described is not to
solve a technical problem or a
scientific problem but actually a
societal norm and therefore leading to
if possible policy reform but you won't
get policy reform until you get the
political clout to want to do
it to reemphasize what one of the things
you said in terms of the challenges one
of the things that I read and I'm sure
you saw this during covid people were
stying to actually write in Publications
and I remember a letter published in
London Times
actually stating why don't we let all
people die from Co instead of shutting
up society that was in the London times
so the fact that it got published is not
their opinion right in a free press you
but it tells you if somebody's willing
to write a letter in a highly visible
publication how many people were
thinking that okay so th that's starting
to be seen if that letter is some
evidence for that people were
questioning in more than one country
quote we're being shut down just to keep
old people alive right that was covid
what is 80% of deaths occurred in old
people and so we've already witnessed
that now the question is what are the
learnings and and I'm a little bit more
optimistic simply because when we look
at rapid technological change and
embracing technology in the past
Industrial
Revolution everybody was
scared all these manual workers are not
going to have any jobs guess what
happened gdps grew new professions got
created then we saw that when we started
to see agriculture start to get
industrialized agriculture was the
primary employer and guess what United
States Europe it's it's a minority
employer now so we've seen this when uh
we first started to see computers come
word processing printing the internet
yeah lots of jobs got
displaced the newspaper industry is is a
relatively minor media industry today go
back to the days of you know the the
Heyday of newspapers it's very different
media become what you do very powerful
reaches far more people so we've seen
this and once people start to experience
the positives they start to embrace the
question really is how much of it was
forced and how much of it was it
people saw the opportunity yeah if You'
asked travel agents 20 some years ago
what do you think of the internet you'd
have got a different answer than the
traveler so I always think how do I get
the the consumer to actually understand
the opportunity and embrace it and then
bring them along that needs to be said
then science provides a solution not the
other way around if we lead with the
scientific argument we're going to end
up in a very scary place because it's
misunderstood so I'm a little bit more
optimistic because I've seen there were
times I'm let me give you an example
there was a time if you go back postor
War II people used to hide a diagnosis
of
cancer there it was a taboo so if you
got diagnosed with cancer you didn't
tell anybody why because cancer was a
lethal
diagnosis if you got told cancer it's
done it's over it took a pioneering
woman who took on the cause of breast
cancer and said I am going to create
public awareness that cancer can be
conquered and the world doesn't have to
be this hiding taboo guess what the
National Institute of Health was created
as the National Cancer
Institute it took a whole movement and
over the next 40 years we found the
mechanisms of cancer and in many cases
today Cancer is treatable and curable
so what what's the analogy that getting
old is um not the terrible thing that we
once thought it was that you can be
thriving and a strong contributor as we
get older most people's mindsets the
consumer you ask tell me what it means
to get old and the first thing they
think about is the visible part of
people that might think it's onset of
dementia pain immobility rigidness they
won't use those words um but all the
negatives that are associated with the
decline in function of our bodies and
Minds as we get older that's the image
so if you ask people you know that is
the inevitable
outcome that's that's what they see and
yet it is clearly evident that loss of
function at the pace that we've seen is
not ubiquitous and certainly not to be
assumed is going to happen to everybody
in fact in the majority of cases it is
likely something that can be slowed down
if not
halted now how do you bridge that
current understanding with the technical
reality of what's possible and one of
the reasons I avoid about saying we're
going to live longer although I'm I'm
not actually questioning whether we can
live past 12 or not I'm a pragmatic
person let's show that we can keep
people healthy as long as possible first
and if one of the benefits of that is
that people live longer so be it but the
primary goal right now in my mind as a
personal opinion is keeping
functionality and healthiness for as
long as possible for as many people as
possible I always add that this is not
for the benefit of a few wealthy people
this should be for everybody if we don't
do that we're going to have a true
societal
challenge you can reboot your life your
health even your career anything you
want all you need is discipline I can
teach you the tactics that I learned
while growing a billion dooll business
that will allow you to see your goals
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today yeah it's very nice way of saying
that we will have revolt on our hands uh
it it does become a dystopian nightmare
very fast if people one class of people
are able to buy their way to immortality
and feeling good and all of that and the
other cannot but it's going to start
there um as you look at this landscape
as you lead people through this
landscape I think that that's going to
be one of the big challenges that you
face how do you think about that right
now in terms of um one what
breakthroughs are real what's happening
right now and then how are we going to
make sure that that is cheap enough that
everybody will have access to
it so first of all let's look at the
fact that there are real differences
which seem to be not just simply purely
driven by biology so if you look at the
differen is in what life expectancy is a
start if you look at the United Kingdom
if you live in Glasgow versus if you
live in London the life expectancy is at
least 10 years shorter in glasgal now
are you saying that's class-based it's
certainly zip Cod code based right we
know that
socioeconomic situation which is
correlated with your postal code or zip
code is an important driver of that how
much of that is choices versus lifestyle
versus the environment you live in all
those are complex now without getting
into the biology of all of those
interactions it's clear that
our human life expectancy and
maintenance of health is D driven by
some factors that appear outside our own
control it's a function of where you
were born and grow up on the assumption
that if you're in Glasgow versus London
or some parts of Chicago versus another
part of CH wherever you look there are
clear
disparities those disparities are
helping us understand what are the
mechanisms driving that we can keep
populations healthy by understanding
those differences that's one Public
Health
population level evidence another we've
seen is populations living in certain
parts of the world the so-called blue
zones clearly have longer life
expectancies what is the difference
there what is it about growing up in
some part of Italy or some part of
Greece or some part of the Northwestern
part of Pakistan and India parts of
Japan all over the world there are these
blue zones what is different about those
populations and it's easy to say well
it's their lifestyle choices but there's
clearly learnings in that so that's the
human evidence now we look at animals we
have observational evidence the
different species live longer but more
importantly starting with very simple
single cell organisms which was first
shown decades ago all the way through
now to primates monkeys we've shown that
interventions
including uh therapeutic potential drugs
not approved drug potential drugs in
some cases drugs that could be
repurposed can change the life
expectancy of otherwise randomized
matched animal groups so that's reason
to believe that this is possible now is
it safe what's the optimal way of doing
this with humans those remain to be
determined the last piece and I'll give
you an example of
this it raises the question if
biological of function has happened can
that decline be slowed or
reversed well if you think about the
evidence from things like epigenetic
reprogramming without getting into too
much of the technical jargon essentially
our DNA sequence our genetic code is the
same today at my age in my 60s than the
day I was born my genetic code hasn't
changed the ability of my cells to read
that code and replace themselves clearly
has changed so the question really is is
is there something wrong with my genetic
code or is there something that is I'm
losing the capability of Translating
that genetic code there's more of it
there than the genetic code because my
DNA is the same and it's all already
been shown by people like yamanaka who
got the Nobel Prize for it that you take
adult cells and you can actually change
them back to genetically flury potential
youthful cells so the code was always
there now there are animal models that
it's been shown in already in
rodents mice and now even in apes and
monkeys that you can take a dis diseased
tissue in a living animal reprogram
itself cells such as in the retina and
restore function and the most powerful
evidence was on the cover page of nature
from David Sinclair's Lab at Harvard
where he took animals that lost vision
from glaucoma and age related eye
disease and restored their Vision by
epigenetically reprogramming their
retinal cells that's powerful it tells
you what we used to think was permanent
loss of vision actually to a degree now
how much of it was restored we can't
measure in an animal but we can show
that it was an animal who couldn't see
light now can
see that gives us a lot of optimism
technically to figure out what's the
next step to go from we went from worms
yeast to ice to
monkeys next step is how do we take that
to humans in a safe manner we're that
close what are the breakthroughs that
you're most excited about in longevity
you know it's a common question I get
that since we're an investment team as
well as a science funding
team if I knew the answer to that it'll
be a trillion doll answer I think there
are several both Pathways and lines of
evidence that excite my team my myself
my peers in other
organizations we're actually approaching
this say where is the highest chance of
success in keeping a portfolio but I've
been in science for 40 years and one
thing I learned is you have to maintain
the
portfolio I'm of a school of thought
that I don't think it'll be a single
breakthrough some people think you know
we're going to find the pathway that
results in age related Decline and we're
going to be able to treat it I think
it's going to be different Pathways to
different levels of emphasis and
importance in different humans and what
we're going to figure out is what they
are and what combinations of those are
most active in you versus most active in
me and if I can personalize it to that
level then I'm likely to address this
and I think the simplistic view of I'm
going to find the elixir of Youth as one
molecule that we're going to put in the
water supply and suddenly everybody's is
so naive to and it underestimates the
complexity of biology and the ability of
biology to adapt we've had a billion
years of evolution of life it has
created all sorts of intricacies we have
to recognize that aging is common to
just about every living species
originating from that one common cell a
billion years ago and if it's that time
meal then it's probably got multiple
bifurcations over the billion years of
life's Evolution we need to understand
this is where Ai and the modern
Technologies where computational
capability and biology are coming
together are going to unlock some of
that it will be more nuanced and
personalized than that maybe in your
case your eyes are aging faster than
your heart in my case my heart might be
aging faster than my liver in another
person we all know people whose body has
age but their mind is sharp we know
other people whose brain is aged but
their body is Young and so we know just
from observation aging is not a single
uniform effect it's a common term for
probably a lot of very diverse processes
which manifest in people in very diverse
ways yeah I hope that gives you some
context it does I'm going to paint a
picture of the future and I want you to
tell me where I go wrong so so uh when I
think about extending human life whether
we're I I'm talking primarily about the
combo of Health span and life span so
this is only exciting for me anyway if
we make 120 just you can count on that
and the way that you can more or less
count on getting to 65 I want to be able
to count on getting to 120 and feeling
like a million bucks okay so if I were
in your shoes and I had to start making
some bets the thing I'm going to be
going from first Prin principles and the
thing I would want to bet on is what are
going to be the things that can identify
the patterns so my base assumption that
everything rides on top of is that the
human body is one to your point it's
individualistic so you have to be
looking at the level of the individual
but there are going to be large patterns
that you can pull out of the data so
while every human is going to be
different I will learn a lot more from
population level um data sets on humans
than I will from um mice right so AI is
going to be able to parse through all
that and instead of us taking these
rough swags that blue zones and what is
it that they have in common it's really
going to look at okay I'm going to take
let's say humans fall into 42 categories
I'm going to break the humans into 42
categories these are the chunks that
they break into these are the people
that age brain first these are the
people that age heart first whatever
these are vascular diseases Peter AA
breaks these down into the Four Horsemen
of death he says heart disease cancer
neuro degenerative disease and type two
diabetes all right type two diabetes is
all lifestyle choices that that is a
self-made problem uh but the by the way
I disagree on that but we'll come back
really yes I'm very eager to hear about
that uh the other three or four
depending on your take um are almost
certainly just predispositions for a
weakness to aging so okay I'm making
bets number one is going to be AI it's
finding the different patterns number
two is going to be how are we going to
go about grouping those um things
whether it's the four horsemen or
something else and then how do we
actually go about resolving those issues
so so much of this is going to be about
vasculature is my gut instinct uh and so
how do we actually go in and address
those one is going to be lifestyle so
just uh whether it's a wearable device
or whatever that tells me to eat this go
to bed here there what whatever and you
remove from the need to think about it
and to know it just tells me what to do
and I do it um but we're also either
going to have to find a way to make
people care less about doing the things
that we'll call bad behavior so take OIC
OIC is a weight loss drug just makes you
less hungry and so you don't have the
sort of human compulsion to go eat that
thing so now you're not doing a bad
behavior that's going to cause you a
problem or I have to create something
that stops the bad behavior from being
bad if that makes sense so those would
be the areas that I would look for
pattern recognition investing in AI um
probably AI again in terms of getting
down to the individual level and sort of
wearable Technologies about what you
should do when at the individual level
and then the last stop on the train
whether it's going to be drugs or other
medical interventions actually going in
at the cellular level and making the
changes so those would be the the three
buckets that I would be thinking about
where I'm looking for the Innovations
what's the flaw in that thinking so let
me add a fourth so there's I wouldn't
say there's a flaw in the three I think
they're all
valid come back to the choices Ty
diabetes we'll come back that for sure
there's a
fourth and that is in the broadest and
we we can get a little bit more specific
in a minute but in the broadest
sense our only real way we measure age
today is bed on your birth certificate I
look at the day you were born and I tell
you this is how old you
are it has almost no um way of
understanding even when I've
aged that these two people are of a
different age and we can all know 60y
olds that look perceptively 80 and we
know 60y olds who look 50 or 40 right so
there's a clear difference some of those
may be choices they've made over their
lives
and uh but people have aged differently
but we don't know how to measure in from
one person to another how do you measure
age okay let alone how do you measure it
at an organ level okay and yes there are
technologies that talk about methylation
of DNA and this and the other but to
measure age in an effective way you need
to be able to measure three things one I
got to be able to measure what your age
is
today however if I can measure your
biological age today that doesn't help
me other than I'm going to tell you
something you probably already know
which I feel older than I am or I feel
younger than I am so it's a diagnostic
with little other utility perhaps
helping you intervene more in Lifestyles
more aggressively with one person or
another I don't know the second thing me
that measurement has to be able to do is
to be able to to predict for me the
gradient and the rate at which you're
aging now that's a much more powerful
meure because if I could measure your
rate of Aging when you were 30 I might
be able to tell you you're on a much
steeper slope than somebody else and
therefore you should pay attention to
this I don't have that technology today
and the third characteristic should be
able to do is it should be able to
reverse if I make the Intervention which
means I can demonstrate to you but
because of the intervention whether it's
lifestyle or it's a treatment or a
device this is predicting you're going
to live 10 years longer
that
fourth variable does not exist today
technologically until that happens we
are not going to be able to design the
clinical trials the therapeutic
protocols the clinical protocols by the
clinicians in the field to actually be
able to do something about it I'm going
to give you diabetes analogy when I was
in I'm an endocrinologist I spent my
professional career treating diabetes
and researching
diabetes if you think about if you go
back to the 70s when I entered Medical
School hemoglobin A1c was not available
finger stick blood sugars were not
available to be able to do your own
blood sugar and even those did not
become useful until it was shown by the
diabetes control and complication trial
that A1C correlated with outcome of
complications now I had something to say
to my patient saying this is your A1C if
you bring it down by 1% your risk of eye
complication goes down by X the
equivalent of that is an exist in agent
so it is going to be very critical for
investment and funding to answer that
question hasn't happened the NIH has not
seen it as its mandate the UK medical
research Council has not made it
Priority to actually invest in
developing the science to be looking at
the so-called biomarkers of Aging with
the three characteristics that I just
showed you somebody's got to do that now
industry won't do it because you you
can't patent these things I don't want
them patented why because if you patent
them you will restrict their general
adoption and you restrict the general
adoption you won't get a standard
Benchmark by which to compare things so
I just want to make sure there is a
fourth pillar the very few people are
talking about and yet it's the key
enabler to the others the other three
you just said are not going to happen
until you get this done so that's one so
should we be investing there absolutely
my organization have we' clearly said
listen you got to go after this and make
sure it's open source why you want the
best signs to be adopted by industry by
the regulator recognized remember and
I'm sure you know the statins didn't
take off until we had LDL
cholesterol it was the fact that we
could measure LDL cholesterol as a
predictor of vascular risk and something
that correlated with reversibility that
risk that you started to see a whole
family of drugs what's going to happen
in agent got to do that that's number
one the second is while these exist we
are free living humans exactly to the
point now how do they interact between
them is it truly a biological
intervention versus a sensor and a
device and at what point does a biologic
become a device and when does a device
become a drug we are actually at the
point with nanotechnology and all these
other new technologies where is
questioning even our scientific
definition of these separations let
alone our regulatory
definition what if it's a combination of
a device and a drug that's delivered in
a certain timed way should that go for
regulatory approval in a as a device or
a drug I can tell you there are
challenges even our regulatory
environment because we don't know where
they
fit we're trying to reverse fit things
where biology doesn't naturally we go
there so it's more nuanced is my point
in that and this is where we're having
to now start to say where can we unravel
some of this complexity and I totally
agree with you big data Ai and large
population sets will help us do that but
at the same time I'm a firm believer in
bringing the policy makers and
Regulators to the table this meeting
we're at today is very much including
that because we need their guidance and
their coming along on this journey to
help us understand so we deliver to
policy makers what they're going to be
expecting and help them shape us and
vice versa so that's where things will
change all right so when I think about
um blood sugar a continuous glucose
monitor uh is whenever somebody asks me
you know what should I do to radically
change my health my answer is always if
you let me put a CGM on you and you let
me dict what you eat simply by the
readings that I get on your CGM I will
change your life in in ways that they
couldn't possibly imagine fat loss being
the easiest but your joints hurting your
sleep patterns all of it is going to be
dramatically impacted by that um do you
is there anything in the literature
because I know you're going to hate the
sort of vague question is there anything
in the literature that indicates what
aging actually is or are we literally
blind at this point to the nature of
Aging I think there's a lot of
literature that tells us what the aging
process is at a cell level very very
strong literature around that a lot of
to a lesser degree but still powerful
literature that helps us understand the
aging process at tissues and organs in
various different organs to different
degrees which sty you know probably the
least understand might be the brain but
in other organs we're starting to
understand that muscular scattle
bone you know is there anything that the
different systems have in common there's
a few for example sence the so-called
accumulation of what the lay literature
is sometimes called Zombie cells cells
that are are not functional but haven't
died and got eliminated sin Essence is a
fairly common phenomenon that we're
seeing tiir elongation is is a common
phenomenon and observation there's a lot
of question marks whether it's something
you can intervene on you know is it
elongation isn't it the shortening of
the telor but elongation sorry is an
intervention y got right and
so those are common which of those are
mechanistically a cause and are
reversible right syence probably is some
of the most powerful literature what
causes sence is it the breakdown of the
methylation of the DNA itself well so
what we know is what senescent cells are
not doing is functioning normally what
we know is that they're
releasing molecules in their vicinity
so-called um you know paracrine effect
local effect of these molecules changing
the function of normal cells recruiting
and attracting inflammatory cells into
those tissues so we know they do all of
these
things why some cells become ccent and
and why some individuals accumulate more
senescent cells than others that has not
been fully understood on the other hand
we have knowledge that certain molecules
treatments drugs can reduce the ccent
load of tissues we also know that
reduction is associated with improved
functionality so our knowledge has
progressed all the way to understanding
that mechanism in this pathway is for ex
an example it is ready and there are
clinical trials going on in humans today
where drugs that actually reduce the
syence load or reduce the impact of that
sence actually are underway today so
that's an example what what's the um
mechanism that they're targeting are
they just trying to kill this inessence
cell or are they actually making this
inessence cell perform better three
lines of interrogation or trials one is
Target and eliminate the siness cell
just reduce the siness set load one of
the challenges there is how do you
identify very precisely a ccent cell
from normal cells and eliminate them
another is to reduce and buffer the
impact of that sinin cell right either
by reducing its function Etc and the
third is change the um decline of the
normal
tissues as a response to that so there's
different Pathways that are being
approached of course we have to remind
ourselves that sin
exists at certain stages in our
development for important functions too
recovering from healings from a wound
require some of those incent Pathways so
completely blocking them and eliminating
them to zero May well be quite
detrimental so what is the sweet spot so
we we know coming back to your question
there are powerful mechanisms that we
can intervene we're learning with
Precision how to do that will that
happen I'm pretty one of the things I
would say I'm confident eventually we're
going to figure this out we're at that
stage right now it's a matter of time
resource and Investments who will figure
that out exactly of course if we knew
that that's the only company I'd be
investing in that we don't know we think
about the mtor pathway right it's a
commonly quoted pathway everybody's
heard or many people have heard of you
know why don't we just give metformin to
everybody and this is you know going to
slow down is probably one of the most
widely used drugs as you know for
diabetes clinical trials in patients
with diabetes has shown that survival is
better in metform and treated patients
near bersel and others have shown in
multiple Publications that this is a
powerful impact it is proposed that
metformin's benefit is working through
the mtor pathway can we come at drugs
that are more
specific very encouraging data including
in humans have we proven it yet and will
everybody benefit from it without
risks and side effects those trials some
of the trials are underway so we are at
human trial stage in a number of these
pathways are you taking met
Foreman one of the things I've learned
to do as a physician is never answer
what I what I take really because you're
worried people will copy you or what
exactly so I you know as I said to you I
I'm an endocrinologist and then the one
of the commonest questions I'd get is
well if you were in my place would you
take it and I always turn around say if
I was in your place I wouldn't be
treating
myself interesting on a podcast that's a
terrible answer I will tell you that
right now uh so here's my take on this
let me know what you think um I've had a
lot of people on the show that do take
that that take a whole host of things
that are getting a lot of praise and I
have not taken any of them because I am
so paranoid about isolating compounds
and I have a very bad feeling that uh so
often something that's marked as a
Wonder cure now a year from now is oh
actually sorry that was killing you and
I'm super paranoid about that I the
fantasy thing that I hold out hope for
is AI and just the ability to
recognize patterns in an
unbelievable volume of data and that
right now feels like the missing piece
to me is we we need a way better
understanding of all the complex
interactions so for instance maybe um if
you are diabetic taking um metformin is
incredibly advantageous and the the
length of your life would have been
shortened were it not for metformin but
if you don't have diabetes taking
metformin now actually shortens your
life it's going to be complex or if
you're getting enough sleep every night
and you take metformin and are diabetic
then it's advantageous but if you're not
getting enough sleep blah blah blah that
you end up with a lot of complex
interactions and until we can look at
the whole data set how much sunlight are
you getting uh genetically how well do
you produce vitamin D like there are
going to be so many complex interactions
that unless you're really looking at
something that's truly n of one you're
never going to be able to figure out
what the right play is and so for me the
thing that I'm trying to do is stay
alive long enough for us to get to what
is often referred to as escape velocity
so that you're you for every year that
you live we now add more than a year to
your life expectancy and so
theoretically you are Immortal I don't
think we're ever going to actually
achieve immortality but that's probably
a different
conversation um yeah so because I'm not
a I don't mind telling people uh what I
do but that yeah I would really tell
people to be wary of isolating compounds
let me respond and react um to one of
things that you said I think which is
very
powerful and it raises a dilemma we have
in society and in the
field clearly if you have diabetes and
unless you have a
contraindication metformin in most
doctor opinions is the first line of
drug we also know as clinicians that if
you are at risk of diabetes and have
impaired glucose tolerance giving you
metformin is likely to delay the
progression to full-blown hypoglycemia
based on a threshold for blood sugar now
it's a Continuum so it's sort of a
artificial biological threshold but we
call that a threshold
right there is no drug approved by a
regulatory Agency for the prevention of
diabetes even today there are diabetes
drugs and we are diabetes drugs that we
know reduce the progression but they're
not appr pro for that there are lots of
reasons for that but one is to take a
drug like metformin do I advocate that
everybody who doesn't have diabetes
should be taking metformin no some
people can have significant reduction in
vitamin B12 levels which has
complications which can cause harm we
know your ability to build muscle from
resistance exercise I'm not talking
about big bodybuilding but resistance
which we know is a good thing is
mitigated if you take Metformin so you
put on less muscle if you take Metformin
so we need to understand not only why
but what is the implication of that for
the individuals who do take Metformin
how do you overcome that right is it
more exercise a different lifestyle so
there are always trade-offs and to your
point we need to understand well there's
a way we can do that can do a randomized
control trial of healthy individuals
look at known age related endpoints and
do a metformin trial why hasn't that
been done well first of all and this is
a personal
opinion it's a drug that's very
cheap 5 10 cents a pill if that no
patent there's no branded version that
is going to sell to make money from it
and so industry for good reasons no
shareholder is going to pay a Company
CEO to go and put lots of investments
into proving the metformin
works on the other hand government
agencies don't typically invest in doing
large clinical trials for generic
drugs it's not on their radar
screen who's going to do it and so I
think one of the questions we have to
ask ourselves in this whole field of
what I look at as repurposing drugs is
when drugs are either near off patent or
have gone after
patent can they be repurposed based on
much greater science understanding after
they've been on the market to where else
they could do that requires a couple of
things one is the funding the second is
you know drug companies compete on my
drug is more effective than yours it's a
good thing right that's the private
sector
competitiveness but it raises a question
should we ask the industry to pull all
their safety
data and and so that for the common good
safety becomes essentially open
source so that as drugs are on the
market we start to understand their
safety profile because the benefit of a
drug is two sides of an equation
efficacy and risk it's both we talk a
lot about efficacy but we can actually
accelerate our understanding of safety
by a lot of this changing and sharing
data even while a Drug's on the market
and then after it's gone off the market
Market really pulling that how do we
bring that about you the AI on just a
population level data set will get you
so far actually studying large data sets
of people who've been treated in
structured
trials will give you a whole other level
of complimentary depth in understanding
but you need to have access to more than
one trial do you see where I'm going so
those data sets and I'm not talking
about the Publications where you do a
some meta analysis is based on the data
that's published but actually getting at
the source data and really interrogating
it will open up all sorts of things now
that raises litigation questions risk
all of those but they're all solvable
the last piece of this data I don't
think we're going to be able to really
unlock the power of AI and large data
sets until we start to understand how do
we do that protecting privacy without
blocking access to it and so that's
going to take without blocking access to
what the data being collected right now
if I went into uh a government data set
in most developed countries and I said I
want to look at the population data set
to really understand this I cannot just
simply go in as an academic researcher I
can look at claims data if the Medicare
for example gives me access to it but
that tells me reimbursement
data claims data only tells me what was
optimized for
billing can I get into understanding
actually what the clinical record showed
not what was built and we there's lots
of literature that shows that claims
data I'm using as an example does not TR
fully represent the clinical data set do
you think people should have to um
assume it was anonymized but should
people have
to reveal their data so uh I'm imagining
a future where um we're we're wearing
our it's it's not a CGM but you're
wearing something that's monitoring your
blood levels on let's say a 100
different variables and uh we're also
tracking mortality so I can see this
person has this Blood profile and they
live this long they have these ailments
they complain about this again
anonymized but do you think people
should ought they I won't even say
legally do you think morally they ought
to give up their data you've raised the
powerful point right and I very
insightful question which is to what
extent do you balance the individual
versus the common good right this
principle allies not only to Medical but
lots of things and there are lots of
areas where we do give up our individual
rights for the common good take
contagious infectious disease we did
this in covid right if you were covid
positive we gave up certain choices in
some countries you actually had a
passport and if it was positive you
could not enter
certain buildings that was we gave that
up wearing a mask was giving up our
individual choice for the common good so
the it really comes back