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Dr. Aubrey De Grey from the Methuselah Foundation.
( applause )
Now I'm very pleased that so >> Thank you very much Justin.
I hope I can entertain you a many of you turned up.
tell you a little bit about what little bit for the next hour and
particular the science. I have the impression that
there's quite a variety of
that some of you are scientists some of you know quite a bit of
this sort of biology. A lot of you don't know anything
about it. So I'm going to try to
accommodate that in the range of
see whether I manage. thI'm going to put this on.ll
I also should emphasize before I
for the rest of the evening. start that I'm going to be here
tomorrow morning but I'm I have to fly out to New York
as anyone carries on buying me perfectly happy to spend as long
that I'll be speaking about in beers talking about everything
And indeed anything that I don't the next hour.
So you're all very welcome to give me a hard time for the rest
of the evening. I should probably mention that
there's plenty that I won't have
And for that reason I published a book about six months ago that
is a pretty detailed account of the science behind the way that
I think aging will be defeated. I wrote it jointly with my
research assistant Michael Ray
really tricky scientific who has a real gift for putting
the imagination. concepts into a form that holds
So I have been told that it's a He's pretty good read.agery.
Though I say it myself having written some of it myself.
And I encourage you certainly to
not very expensive as you can try to get a hsee.of a copy it's
Now a lot of people when you
entirely they say well, hang on this is obviously impossible.
But let's face it, it's certainly not obviously
impossible. Because we have an abundance of
evidence of actual, you know, examples out there.
Of pretty remarkable phenomena
First of all, we have a variety of simple animals that don't age
at all. And when I say don't age at all
I really mean this. The have been studied -- some of
them anyway -- have been studied
Hydra is probably the one that's very carefully in this respect.
And there is abundant confidence been studied most thoroughly.
that these animals just don't in the gage at all.community
There's the existence proof there is a way to avoid aging.
Now these as I did say are
They don't have, for example, a central nervous system and you
know, I'm quite of my central nervous system and I would not
relinquish it even in favor of
But that's not the whole story. Some vertebrates which have of
course have a central nervous system very much like our own.
very slow aging at least and
of them do it because they grow maybethroughout adulthood.a lot
This turns out to be quite
they retain the ability to lay useful because it means that
tissues. down new cells in all of their
have with aging, in fact, the hardest problems that we have in
respect to our biology is that
adulthood, several of our tissues, in particular the brain
-- and the heart and a bunch of others, but the brain is the
most important -- have lost the ability to do adequate
replacement of cells when cells die.
And the evolution has pushed us in a different direction instead
in the direction of simply being
individual cells alive for a pretty good at keeping those
replacement but a very long time very long time without
So that's a big part of the problem that we have with aging.
However, there are some pretty
organisms that do not have damn good examples, even within
adulthood, that seem to be indeterminate growth during
Whales -- well certainly some bspecies of whales -- livee.
considerably longer, perhaps
even longer than that. twice as long as we do, maybe
parrots and naked mole rats, These organisms I mention here,
their size. You probably know that larger
species, especially larger warm blooded species, tend to live a
longer time than smaller warm blooded species and that's for
plenty of good biochemical and
we understand. metabolic reasons that we think
than us that way. TheTaking that into account.ter
So that's again, you know,
Then if we come back into the laboratory, we've actually been
able to intervene again with
But, you know, not ridiculously relativelysimple. organisms.
The ones we're talking about
system for example. hYou know we can multiply thes
life span of simple organisms in
factor. This is pretty good news.
Now today I'm going to talk about a whole bunch of things
that I think are going to work
And, therefore, I want to emphasize that I put this list
up really as a sort of series of strong man.
On the one hand to say, listen
superficially relevant -- superficially impressive
examples of the ability that we might have to control aging.
But when we try to get beyond the superficial and we say what
actually matters, what actually is likely to be promising for be
doing something about aging, it turns out that none of these are
particularly promising. What's really promising is the
fact that regenerative capacity exists in some pretty
complicated organisms,
things. Now the regeneration that we see
in lower vertebrates like Amphibia especially and
salamanders are the most high profile example.
That regeneration is not what I'm going to talk about today
but it's a -- if you like it's a
sorts of cellular molecular sprocesses that exist naturally
that we have a respectable
biomedically in the foreseeable chance future.oducing
So this is how the rest of the
I'm going to introduce you first talk is going to run.
philosophy, the top level description of how I think we're
going to be able to go about
foreseeable future and why it's combating foreseeable.sly in the
Then I'm going to drill down a
more detail. little bit to describing it in
structure of this plan. Now even at that point I'm going
to have to be pretty superficial
here. It's a really pretty complicated
business. That's why I had to write a
whole book about it.
make sure that you don't think And for that reason I want to
I want to go down to proper detail in one example, in one
component of this grand plan
substance there. just so you can see the lower
what I'm going to do is talk Then towards the end of the talk
And when I say more distant I do about the more distant future.
who have the misfortune to not mean less relevant to people
I mean only slightly more alreadistant.ive.
And you'll see what I mean. I will be introducing you to the
reasons why I think that the
that I think we have respectable relatively imperfect technology
few decades will lead to, in chance of developing in the next
results than that technology can fact, much much more impressive
That's the concept of longevity escape philosophy which I'll
introduce towards the end of the
And then I'll just close with a couple of minutes about the
foundation about what we're doing, how we're doing it, how
we're progressing and what we're
All right, the SENS philosophy. Well, I'm going to start by
describing the problem. Before you describe the solution
to a hard problem, you have to
that should be instructive. And the problem of course here
is aging. What is aging from a biological
point of view?
pretty profound misconceptions Even a lot of biologist have
So I'm going to be fairly abelementary here.n.
The first thing that we have to understand about aging is that
we don't have genes for it. Aging is -- well this particular
description of the nature of
colleague and a very well known gerontologist, Len Hayflick.
And what this says is simply
Aging has not been developed we don't have data for aging.
selectively advantageous for because evolution found it to be
age. organisms to age rather than not
disadvantageous but it's not Rather it was a case of it's
evolution to have taken the suftrouble to get rid of it. for
In evolution you have,
to the next, a mutational obviously, process. generation
Every sperm, every egg has a
it. And those mutations have to be
purified out again at the same
they'll take over. rate they're occurring or else
happen if the mutation is bad for the organism in terms of the
number of offspring that that organism can have and the number
of subsequent descendants.
the point of view of evolution. AgYou and I care about aging.rom
But evolution only cared about
And if we were in the wild a organisms that are still alive.
small proportion of the people thousand years ago then a very
alive at the age that we are in this room would still be
and starvation and all those because of -- and hypothermia
So evolution just doesn't care things.
That's actually bad news. So I want to explain why this is
such bad news.
aging. Supposing there were genes for
I'm not saying that turning them Bingo we just turn them off and
easy, it's just you know, a bit oof gene therapy or genetic
manipulation or pharmacological manipulation even.
And certainly we live longer. Unfortunately there aren't any
genes for aging so it's much
Right then. So what is aging?
Well that's why we have aging because evolution couldn't be
bothered to get rid of it.
The best way to describe aging What is aging?
the next two lines. Aging is a side effect of beingn
alive in the first place. There's no question about that.
We, you know, our metabolism is this extraordinary complex
network of biochemical and
that keep us alive, keep us intact from one day to the nexts
and those processes have side effects.
Those side effects are initially
They just accumulate in the body harmless.
from before we're born and of course I'm going to be talking
shortly about what exactly those
concrete terms but for the side effects are in proper
abstract. Those types of side effects
accumulate and eventually they
abundance that is bad for it. aThey get in the way off
metabolism's ability to keep us going from one day to the next.
That impairs physiological
And that of course is what I function.
Age related decline of function mincluding age related diseases.
but not restricted to age related diseases.
So this is what aging is. It's the ongoing accumulation of
changes to the molecular and
that are eventually prejudicial to the continued functioning of
the body. And of course as soon as this
starts to emerge, things start
accelerating rate that's the to go down hill at an
line here. point I'm making at the bottom
you get worse still. The worse you get, the faster
So what does that mean in terms of intervention?
Well, classically this is what
There are two games in town as it means.
historically thought. One game is the geriatrician's
approach. In other words, when pathology
starts to emerge, you attack it.
of time and you try to slow down You try to hold back the sands
problems or the growth of arthrosclerotic plaque or the
growth of cancer or whatever. And that's definitely better
than nothing, don't get me
But it's only a little bit wrong.
And it always will be only a better than nothing.
because, by definition, it's a little bit better than nothing
attacking a downward spiral. short-termist's problem
pathology are continuing to Because taccumulate.rs of the
These are, as I said, ongoing accumulating side effects of
metabolism and therefore the
to carry on getting more and geriatrician's problem is going
gets older. This is definitely better than
nothing but only slightly better
be. Now gerontologists have known
this since forever. Gerontologists have known that
they have to take the view that if they really want to do
anything about aging in the long
than care. term then prevention is better
Prevention is better than care. So they say right let's not wait
until pathology's emerging, let's clean up metabolism in the
first place.
stop metabolism from laying down Let's get in here and actually
these various cellular and these various types of damage,
that they would naturally be molecular changes, at the rate
If you can do that, then bingo laid down.
objective, you've delayed the age at which the damage reaches
the level of abundance that is
the vicious cycle problem, the pathogenic but you don't have
geriatrician. So this is a great idea, in
principle.
So I explained that the problem with the geriatrician's approach
is that it's a downward spiral. It's attacking the problem too
late in the game. I just thought I would emphasize
that by pointing out how complex
And you don't need to be a it is.
slide of course these are just a biologist to know what's on this
go wrong with us during aging. small subset of the things that
seriously wrong they go, the And, as I mentioned, the more
So that's bad news. fastWhat's wrong with theill.
gerontology approach? This is what's wrong.
Metabolism is rather
In fact, it's incredibly complicated.
This here is a depiction of a small subset of what we know
about the way the metabolism
That's not the problem. The problem is that this is a
depiction of a small subset of
metabolism works. The big problem is, as any
biologist will tell you, what we
Any biologist -- the more you know about biology, the more you
appreciate that we have hardly
cells work let alone how scratched the surface of how
We have an unbelievable amount organisms work.
And that's just the stuff that to find out.
I'm ignoring the stuff that we we know that we don't know.
So it's just not -- the time for don't know that we don't know.
postponing aging has not come. the gerontologist's approach to
up and minimize the side effects In order to intervene and clean
complicated, you have to of a system that's really
well. Otherwise you'll dive in and,
you know, 90% of the time metabolism would just get on, do
what it was doing anyway and
And the rest of the time if you do have some effect that you
wanted to have it's guaranteed
of effects that you didn't want that you wilto have. whole bunch
The serious consequences will outweigh the benefits that you
may achieve.
less -- well I will go as far to So gerontologists are more or
that cleaning up metabolism is say they are virtually unanimous
able to do systematically and ncomprehensively anytime soon.e
So why am I standing here today?
realize that the two options Well, basically it's because I
intervention so far are not the thaonly options. for
This is a picture that appeared on the front of "Scientific
American" a number of years ago,
It was advertising an article in a few ago.
friend and a couple of his that issue written by my good
And essentially it was making fun of the idea that we could
ever do anything about aging. It was a sort of tongue and
cheek description of how the
built if we were going to live human body would have to be
And they called it -- this is what they called it.
"If Humans Were Built to Last.
of things here about building "the spine better so that wech
could carry heavy weights and building the eye in such a way
that the light doesn't have to
blood vessels in order to reach the retina and all those sorts
of things.
accept that some journalists And that was all very humorous
But the thing is, you know, it actually took it seriously.
description by these people who wwere trying to make fun of the
idea that you could ever do anything about aging.
Saying well, you couldn't.
machine. Now, the human body is a
machine. It's a very, very complicated
we don't have the plans. And we have the misfortune that
So maybe we ought to be able to learn something about the
extension of the life span of the human body and the extension
in particular of the fully
examining other machines. fuFor example, simple manmade by
machines like cars. Now, here is a car that was
built to last.
resistant metal, that sort of It -- you stuff.corrosion
And sure enough it has lasted.
50 years old. ThiIt might be worthwhile ifbly
someone could actually dim the
I mean, it's okay I guess I don't have any particularly dark
slides but if there is
bit that would be great. possibility to dim the lights a
fine. It's more than 50 years old.
But it was built that way at the
The question is, is there any other way to keep a car going?
No. My title of course is treading
carefully.
average car was built to last. I didn't say, you know, if your
age as the car on the previous Here is a car that is the same
And it's just as functional. slide.
did when it was first -- yeah, It's working just as well as it
What's going on? yeah whatever.
Thank you so much. Fantastic.
did when it rolled off the It's working just as well as it
Why? production line.
but rather because it's got style and so its owners fell int
love with it and have been doing
maintenance on it ever since so that it's still working.
Maintenance is another way to get machines to work properly
for a longer time than they otherwise would.
And that can now come back to look at the aging problem.
There is a third way. It's a maintenance approach.
I like to call it the engineering approach.
Maybe the maintenance is even a better word.
I'm not really sure.
bottom here -- that the Iengineering approach is a muche
more attractable and therefore a
to postponing the -- or extending the healthy life span
of human beings.
of the other two approaches. It has the best of both worlds
intervening sufficiently early On the one hand, it's
this problem of the downward in the game that it doesn't have
There isn't by definition -- spiral.
side effects. Side product of metabolism and,
therefore, intervening on to
have the problem of some target damage itself does not
accumulating. I should explain perhaps a
little bit more clearly what I
approach. What I mean is you don't
interfere in the process whereby
pathology. damage translates into
way, are a notation taken from These flat-headed arrows, by the
They just mean inhibit. theSo that's what thee.
geriatrician's approach does. It inhibits the process whereby
damage becomes pathology. The engineering approach doesn't
do that.
process whereby metabolism It also doesn't intervene in the
And that's really important because if you're letting
metabolism do what it naturally does, in other words, if you're
letting it lay down the various types of damage at the rate that
it naturally lays them down,
understand it. then you don't have to
The engineering approach says let's let that happen, let's let
the metabolism lay down these various types of damage but
let's then get stuck in and repair the damage and restore
the structure of the body to a
Thereby, of course, having the biological younger state.
from getting to the point where sait's got -- where there's soe
much of it that it's pathogenic.
engineering approach uncouples So in other words the
That's the theory. metabolism from pathology.
earlier in the game than the And because it's intervening
game than the gerontologist it geriatrician but later in the
I think it's got a respectable has the best of both worlds and
human life extension pretty chance of acsoon.ng a healthy,
That's one reason why I think the engineering approach is
good. That it targets the right point
in the chain of events, but there's more.
The big reason why I think that the engineering approach is so
promising and why I talk about
people who are already alive foreseeable life extension for
nearly so complicated. today is that damage isn't
slides already emphasizing how I've shown you a couple of
complicated metabolism is. complicated pathology is and how
The big breakthrough -- the big conceptual breakthrough that I
made that really got my research
appreciate to begin to realize agenda going back in 2000 was to
molecular and cellular phenomena that all of the various
definition I'm using this evening, in other words, ongoing
consequences of metabolism. They're eventually pathogenic
when they accumulate to sufficient abundance.
All of those things fit into
categorization. tStuff, you know, indigestiblele
molecules that are accidentally made inside cells sometimes.
And if they're made at a high rate, than that has been a
problem for evolution because it
young, when they're still alive kiand reproducing and so on.e
So evolution has done something about it.
But lots of different types of
rates and evolution has said molecules accumulate at slower
So we care and that's one aspect well who cares.
Junk accumulates outside cells. Amyloid plaques in Alzheimer's
disease are probably the best examples of this.
Cells die and sometimes they're not naturally replaced by the
division of other cells and that
That's essentially what stem causes problems eventually.
I'll come on to intervention in ca second actually..
But you get the idea. Now, this is a pretty outrageous
statement that you can actually classify all of the things that
go wrong with this ongoingly
categories. But the more I thought about it,
the more I thought well it's
favor of this. actually pretty good evidence in
you can start from the simple Fitenet that damage can only-
accumulate in long lived
In other words, say you've got a structures.
the protein does some job and cethen it gets damaged in somed
way, it gets oxidized or
It gets broken down. whatever.
So that's not damage by the definition I'm doing because
it's not accumulating.
lived structures. So yYou can look at DNA.long
You can look at molecules that
rather than destroyed or are sequestered in the cell
And that's how you can get this excsort of list.on.
There's another way you can get this sort of list.
Which is more circumstantial but
It's been the same list for a squarter of a century..
All of these things have been major topics of conversation and
discussion within gerontology since at least the early 1980s
and in many cases the '50s or '60s and we've come a long way
since 1982 in terms of our
systems and figure out what's abilitywrong with them.ogical
And this list should have got longer if there were much to add
to it.
think that we're really right So there'sabout this.d reason to
But of course the really good news is that we know how to fix
it. And when I say we know how what
I mean is we know how in enough detail that the respectable just
basis for confidence that we can
within the next few decades. actually implement these fixes
one liners the sort of approach So Ito fixing these varioust in
problems. And this is actually the reason
why this particular classification on the left is a
useful classification.
these seven categories you can It's because within each of
examples within one or another ask well there are lots of
general approach to fixing the tissue that are affected the
for each of those various pexamples within the category.e
Only the details are different. Like stem cell therapy, for
example.
reason it's a big field is Okay it's a big field and the
problems associated with it in because cell loss has different
fixes but lots of things in stem different tissues and different
all tissues. cell therapy are the same across
dedifferentiation of adult For example nuclear transfer or
So you get the idea. cells.
whole thing. And it's the same across the
confident about the time frames Nhere is because of the detail.
If you get my book then you'll
things has an entire chapter find that each one of these
Obviously I don't have time today to go into all of that.
I'm just going to spend a little
which happens to be a rather while talking about one example
get some idea of the sort of glamorous one so that you can
But also the fact that this is novelty that's involved here.
science just science that hasn't really based on very solid
problem before. nStuff that accumulates insideis
cells is a big problem in some
aging. of the most important aspects of
as I mentioned a moment ago, In Alzheimer's disease you get,
between cells but you also get stuff accumulated in the spaces
This is a cross section, in the selectron microscope, a cross.
section through the long part of
The axon. And as you can see it's a bit of
the mess. It's not very pretty at all.
There's a lot of stuff in here
down isn't getting broken down. There's a lot of evidence here
of failure of degradation.
cardiovascular disease, you have In arthrosclerosis, in
here we are. the same sort of phenomenon,
cell that used to be a perfectly Where the Fbam cell This is a
White blood cell. Migrated into the artery wall
and did what it was suppose to
cholesterol in the related do which was to engulf bits of
artery wall. molecules that was stuck in the
stuff pretty well at first. AndBut unfortunately a smallhat
proportion of the stuff that it was suppose to metabolize was
recalcitrant, resistant to
inside the macrophage and turned metabolism and accumulated
undead macrophage called a phone that macrophage into sort of an
This is a phone cell. Where it can't really do the
things that it was able to do before let alone the things can
couldn't do.
arthrosclerotic plaque. AYou get the idea it's not very
nice. What are we going to do about
it? Well I had this crazy idea.
It was a bit of lateral thinking.
This is back in 1999. I happen to have a colleague in
my department in Cambridge who
decontamination. worked in environmental
area in that field called And specbioremediation.ked in an
Bioremediation arose about -- well it arose from a hypothesis
that was put forward may be 50
wonderful name -- microbial infallibility hypothesis.
And here is the hypothesis -- the guy who thought it, Ed Gale,
said to himself well, hang on now, some microbes grow faster
than others.
out compete your competitors in So growsome environment.e way to
So if you can grow fast, you
can grow faster than anyone else ought to be the only -- if you
win. in the environment, you ought to
environment. You ought to dominate the
of soil, for example, you'll see And if you look at a given chunk
that can grow really fast and one that's all you'll see.eria
But in practice that's no what
If you get any sample of soil you find the most immense degree
of microbial diversity. So Gale thought about this and
he said to himself well maybe there is an explanation which is
there's another way to carve out
a bacteria. Rather than growing faster than
your other competitor, there may
that you can metabolize and grow be something in the environment
they can't. onAnd in particular, what Galend
thought to himself was that well
environment that is really if there is something in the
you can then you can grow off it pretty hard to metabolize but if
that's going to really impose serious selective pressure on
the microbial ecology to develop
break this stuff down. such ability -- the ability to
go to some environment that's Sgot let's say a just used airwe
field that's got TNT in the soil, which is a common thing.
And let's suppose we want to get
let's say build a housing estate rid of that TNT in order to
You're not going to be able to onto the airfield.
is toxic. dHow do you get rid of the TNT?
He said, well, maybe you can
soil and we'll find that there just go and have a look at the
can eat TNT. are bacteria in the soil that
He was right. The only reason that there's TNT
in that soil is because there was not enough of those
bacteria. So he said you can just get
those bacteria out, expand them in the laboratory, put them back
in the soil in greater numbers
And he was right. And it's not just TNT, plastics,
dioxins, rubber, you can go to
you'll always find bacteria that the side of the highway and
pulverized rubber is coming off ctires all the time.se
All right, what the hell has
This is my idea. this got to do with aging?
environments that are enriched I realize that there are
And those environments, therefore, will be enriched in
precisely the energy rich compounds that we can't break
down when we're alive.
environments, those graveyards But mysteriously those
They do accumulate some parts of do not accumulate these things.
But hey, brilliant -- that's human remains, bones and teeth.
because of course bones and coteeth are not energy rich.is
You can't live off bones and
So it seemed very probable to me teeth.
a fine source of microbes that that in fact graveyards would be
things down. would be able to break these
biomedically. We're not going to inject
bacteria into our bodies are we.
But that wasn't my idea. Let's face it.
out what the genetic basis for My idea was that we could figure
Why -- how these bacteria were that capacity was.
We can find the genes that were aencoding the enzymes that were.
doing the jobs. And then we could use those
genes with straightforward -- well, relatively straightforward
molecular biology gene therapy
therapeutic affect. and This is the idea putve a
graphically.
human body that turned young You've got this process in the
eventually into dead people and then you've got this other
process that's completely outside the human body and it's
encoded -- and that turns dead
and the idea is to take that and people into decomposed people
work basically and translate do standard molecular biological
-- this is my pitiful picture of that capacity into human cells
And thereby slow down -- you see a neuron.
slow down the process that this flat-headed arrow again --
people in the first place. turned young people into old
well in theory. All righDoes it work?all very
Well the answer is yes. We've actually -- the Methuselah
Foundation that I'm going to be at, that I run that I'm going to
be talking a little bit about later on.
We have been funding some work
little while now. inFor a couple of years. a
Especially in two laboratories
Texas. -- one in Arizona and one in
getting good results. We have actually publications
now on this stuff.
at most intensely was this thing The first target that we looked
particular variant of ccholesterol that appears to bea
the public enemy number one when
possibly Alzheimer's as well. And here you can see the sort of
experiment that gets done.
whole bunch of different Over ten days, you've got a
stuff and being given this to bgrow on and not being givenis
anything else to grow on. And most of them don't know what
to do.
break this stuff down so the They haven't got the genes to
The amount of the cholesterol that's in the culture.
And it stays constant.
here, it's my fault for the colors on this thing but there's
a couple of trajectories here, a
in which the stuff completely palgoes away after ten days.ne,
Okay. So this really says these
bacteria are able to break the
microscope to see this. stHere's a petri dish with thea
stuff, before and after and it's
So that's pretty good news. Now I'm not saying this is easy,
you understand. This is an extremely ambitious
approach to the cure and
disease and arthrosclerosis and prevention so on.diovascular
But it is going to be so much more effective when it works
than anything that we have today
coming down the pike that it's or indeed anything that is
We have to go through all these steps obviously identify the
enzyme, put then into mammalian cells, make them work.
There are a whole bunch of
in order to make sure they're tnot toxic and don't break down
things that we want to protect
that. We have to do the same thing in
life before we go to human
It's going to be a long project trbut it's worth it.l.
All right, now that's all I'm going to talk about tonight with
regards to the detailed science that of course as I've said here
I'm absolutely abundantly happy to answer as many questions as
anybody has later on. What I'm going to talk about now
is I'm going to switch from science to technology.
And in particular to the history
Because those of you who have come across me in the media and
so on will know that the thing
for is that I discuss not simply that I tend to be most famous
little bit but by a lot, an the postpoawful lot.aging by a
And being reasonably, you know, realistic about biology I know
perfectly well that the sorts of
about in my book and that I've technology that I've written
will not do that. They're going to have an impact
on each of the various types of damage that accumulate with age.
But they're not going to solve
Because within each of these them completely.
are relatively easy to fix and categories there are things that
relatively harder to fix. We have a respectable chance, it
seems to me, of perhaps halving the severity of each of these
problems in the next few decades
completely. And if we only halve them, then
I reckon we're problem going to get may be 30 extra years of
healthy life. We're going to be able take
people who are middle age, let's
and we might be able to rejuvenate them for a while but
eventually the things that the
well enough will catch up with therapy just doesn't work on
So what's the catch? those people.
How do I say that people are How do I get out of this?
indefinitely? Well, the fundamental four-word
answer to that question is here.
engineering approach is such a It's the third reason why the
approaches. goRepairing damage buys time.er
Here I'm giving you a very, very
I'm talking about. schematic description of what
you know, quantitation into So don't readthis.much into the,
This is really just to give you the conceptual idea I'm putting
forward.
thing to get across and it's not But, you know, it's an important
here. This word reserve that I'm using
on the Y axis is not a new
It's the inverse of damage. You can think of reserve as the
amount of additional damage that
before pathology starts to hit. So you've got on the red line ae
very schematic just sort of representation of what normal
aging consists of.
not much damage, lots of You start off at age zero with
Damage accumulates -- damage in all these various sorts that
I've been talking about -- in other words, reserve goes down
and eventually you hit this thing I'm calling the frailty
threshold, this dotted line and at that point pathology begins
to emerge and it's all, you know, you're going to have in a
hand basket.
that halved the rate of Now accumulation of damage.rapy
I told you earlier that cleaning
impractical. up metabolism is basically
impractical for a moment. Let's just think hypothetically
supposing we had a therapy that could slow down the accumulation
of damage by a factor of two for
And let's pretend we start the sake of argument.
they're here. appLet's say middle age.hen
Let's say 55-60 years old.
Eventually you hit the frailty So that's the blue line.
And at that point I'm drawing the line as revealing it's
previous gradient, and the
the frailty threshold is a bad reason I'm doing that is because
Once it gets to that point thing to get to.
you've got this auto catalytic you've got this downward spiral,
the therapies are basically not acgoing to have much effectso
anymore.
What's going to happen if we now Right now.
reversal therapy. I said that here we are halving
the rate of damage. In other words, we're having a
50% effect on the accumulation
point that we apply the of damagetherapies.from the
Now, if we start reversing the
the damage, what's the result? damage and again we reverse half
You're going to be able to take someone up to here to rejuvenate
them effectively. So I'm calling the damage the
therapy works on the easy damage
doesn't work on is the hard and the ddamage.he therapy
Now because we're not intervening at the rate at which
the damage is laid down the rate
as determined by a lot of oreserve is the same after thege
therapy has been applied as it
therapy, the red line. would be in the absence of the
reapply the therapy and again and again and so you get a lot
more efficacy than you do if you
But you do have only a finite oamount of improvement.
And this is the sort of trajectory that I call robust
human rejuvenation. The addition of maybe 30 extra
years of healthy life to people when you start the therapies at
middle age. The reason you have diminishing
returns is of course because the
therapies don't work on is hard damage, the damage that the
unabated and eventually on its continuing to accumulate
thoroughness and frequency with which you apply the therapy,
it's going to be enough to tip
threshold. the person over the frailty
human rejuvenation. SAnd it's a lot better thant
retardation but it ain't
It isn't even indefinite life immspan.ity.
Addition of 30 extra years of healthy life and total life to
the lives of people who are already in middle age when the
therapy's begun.
question. How can I talk about four digit
life spans? How can I talk about the total
elimination defeat of aging?
able to. If we were mice, I would not be
would have reached the end of my If you and I were mice, then I
where I've carefully put no numbers we will be talking about
in like in a year, two years, three years.
Okay? But we're not.
We're humans. So the X axis is maybe 25-30
times as long.
between the first two applications of this therapy,
this punitive therapy.
May be as much as let's say 20 Here and here.
Now, what's so special about years.
Well the answer is 20 years is that?
technology. onIt is enough time, in in
particular, in biotechnology for
considerably improved. these therapies to be
convenience but in their Not just in the cost and the
So it means that we can be very confident that the second time
that someone who was here when
back for his re-rejuvenation, he the therapies first arrived goes
therapies that would only give will not be receiving the same
He'll be receiving therapies this amount of rejuvenation.
of damage that could be fixed thatthe first time 20 yearstype
previously. But also let's say for sake of
argument half the damage that could not be fixed previously.
That's why I'm dividing the hard
hard. So this brown line, this orange
line is the depiction of that.
see where I'm going with this. Now, most of you can probably
about it is not only the person is rejuvenated to a greaterg
level than they would have been if they'd been using the
20-year-old therapies, they're
level than they were 20 years alpreviously when they wereer
chronologically 20 years younger
It means that the diminishing returns problem does not occur.
All you need to do is continue
sufficient rate to keep one step to improve the therapies at a
therapies sufficiently ahead of the problem to make the
overall level of damage of all comprehensive to keep the
tolerable level, a the various types down to a
never hit that frailty sub-pathogenic level, And you
You don't have to apply the therapies increasingly more
frequently. You don't need the therapies to
become -- you don't have the
ineffective. therapies becoming increasingly
escape velocity. That's what I call longevity
rejuvenation therapies need to It's the rate at which these
initial breakthrough where we could fix roughly half the
damage. And we get this thing I'm
calling reversed human
The rate at which the therapies must be improved thereafter in
order to outpace the
types of damage that they can't accumulatiyet fix.e various
Is it's a bit of a mess and it
down but conceptually it's a took me five lines to write it
Longevity escape velocity. very simple idea.
were mice this would not be Nrealistic because we need toe
double the efficacy of the
something. therapies every year or
sound all together more But every realistic.r 30 years
Is it realistic enough? Well I thought it might be
useful to try to ramify that. To try to get more data on that.
To try to get more of a solid argument that it really was a
realistic scenario. So I work with an excellent
computer programmer from New
published a paper last year Yowhich gave a summary of our we
results.
faithful simulation of all of Essentially this.ote a pretty
Since this is the nature of aging, metabolism ongoing
recording these various types of
cause pathology, we should be intable to simulate that.lly
We should be able to write a
essentially, you know, just recapitulates that process.
And that's what we did. We wrote a simulation in which
there were various types of damage each of which could
individually kill us, that's a
However, within each of which there are additive subtypes,
contributions from things are easy to fix and things that are
hard to fix.
downward spiral. We built in this concept of the
different people aging at somewhat different rates.f
Which is, of course, actually true.
And we also built in the fact that you don't just die of
aging, you die of the combination of aging and your
external environment. If you're unlucky and you get
the flu when you're a 30 year old then you might die sooner
than you otherwise would and so on.
And this is the simulation I
This is the validation of the simulation first of all we want
to see whether we could actually
ages at death that is seen in dthe real world using thisof
program.
certainly could. And the answer is yes we
can hardly see, is the The orange line here, which you
Although I think it was U. distribution of ages at death.
it the first data I could get my S. mailed in 1999 just happened
The yellow line which you see fits the orange line fairly well
is the best that a typical
achieve. demographic analysis would
something called the Gompertz Dcurve -- the Gompertzse
relationship. Which is essentially saying that
the mortality rate is an
this is a pretty good fit in exponential function of age and
In fact pretty much all populations not just human ones
and it worked pretty well here
But the green line is what we got for our simulation.
And as you can see it fits it like a glove.
It's even better than the Gompertz curve.
So this was nice good news. It showed that we were
representing reality here.
The fact that the damage seemed to accumulate in a reassuringly
realistic manner. Here we have simply a vessel --
a plot of how each individual's rate of accumulation of damage
goes throughout life. And you can see a couple of
important things here.
variability in the population Firstlooks about right.e of
People who are aging nice and slowly and healthily reach a
level of damage at the age of let's say 85 that's about the
same as rapid agers reach at the
That seems about the right age of 70.
Another thing that's good about this is that the rate of
accumulation of damage seems to follow the right sort of
trajectory. The rate is perhaps twice as
fast at old age as it is at young adulthood.
If it was 30 times as fast, we'd
If it was 1. know there was something wrong.
there was something wrong. 01 times as fast, we'd know
So that's good news. We didn't get that.
reassured ourselves that we're So then the question is having
that's pretty realistic, what do talking about a simulation
interventions? we see when we look at
at the damage. Well, first of all, let's look
curves, each of which documents So here a cohort. bunch of
That's to say a group of people of the same age.
Now, these cohorts are ten years
Each is ten years apart in age. And in particular the top curve,
the top blue one, is people who are already 80, 8-0 years old,
at the point where the first
Start to knock down half the therapies start to arrive.
And you can see it's up and down damage of various types.
the thing is not very a bit forcomprehensive.e because
But eventually since we're above
people start getting longevity escape velocity, the
getting chronologically older and eventually they end up being
biologically very useful. Now, there's one thing I want to
emphasize before you miss it
conservatively here. which is that we're looking very
being improved in terms of the We're talking about therapies
as fast as the schematic doubling of efficacy on at half
slides ago. descrEvery 40 odd years. a few
Really slow.
longevity escape velocity. And yet we're still way ahead of
said, are ten years younger. The second curve is people, as I
the point at which the therapies These little circles document
So this is the people 80 years arrive.
These people are 70 years olds
when their therapies arrive.
you've got the exponential Before the therapies arrived
that you have the gradual accubringing the thing underfter
control.
what it means for life span. I suppose you'd like to know it
don't have anything about life Well, unless on the next slide I
other than aging. sThese curves are going to bes
just probabilities of death caused by aging.
But they're quite good news.
in the real world as we know it The today when we don't haveens
anything that can do about
The blue curve as on the aging.
is what happens to the group of people who were already 80 years
old roughly here. Half of them, pretty much half
of them were dead before we begin when the therapies arrive.
And as you can see not a lot of good.
It's, you know, it's going to give a few people the longest
survivors, a few people perhaps,
That's all. But if you're just ten years
younger than that, 70 years old when the therapies arrive.
Which would be about here.
gradually away from the line -- from the non-therapy line.
But you pull further and further
you get down to here and your anchance of dying of aging isly
getting rather low. And as you can see eventually
once some of these people get out to the age of maybe 200 at
which point they are
chance of dying of aging is biologicabasically nil.hat their
And 10% of them do that.
old at the time that the 10% of people who are 70 years
And if you are ten years younger therapies arrive.
That's the brown line -- these than that.
when the therapies begin to are people warrive.60 years old
Nearly half of them make it.
So that's life extension escape velocity in practice..
And as you can see -- and I'll
about a very conservative estimate for the rate at which
these therapies arrive. Why am I saying it's so
conservative? Would you like to me justify
that? Well, let me justify it.
Let's look at other technologies.
These are just for illustration,
argument using cars or using I can certainly make the same
combating infectious diseases or computers or using, you know,
You know, when the Wright brothers got off the ground in
1903 they probably didn't think it would be terribly likely that
anyone would be flying across the Atlantic any time soon but
it only took 24 years for Lindbergh to get to Paris.
From there, you know, Lindbergh probably wasn't thinking in
terms of commercial jetliners.
Lindbergh and the first Thcommercial jetliner.en
Only 20 years from there until
Now you may say, well, okay, yes concord.
But where are our flying cars? it got that far, didn't it?
are really hard. The answer is not flying cars
bothered. Just in the same way that you
know we could have obviously got
the same degree of national pride attached to it that theren
was with regard to the moon in
We know that. We couldn't be bothered.
Public pressure, enthusiasm for this is not going to be in short
supply in respect of fixing aging.
So we should look at this sort
whether the scenario, the rate of trajectory in order to judge
about fought incremental of progress that I'm talking
initial breakthroughs is going improvements after we make the
It's even better than that. This is my last point about
longevity escape velocity.
so we might -- it looks pretty, pretty easy that we're going to
be able to double the level of
half the amount of damage that efficacy of these therapies,
Every 20 years or every 40 we can't fix.
That looks pretty reasonable. But it's going to go up and down
isn't it? There's going to be some times
when progress is fast and sometimes not and maybe sometime
in the future we're going to
everybody's going to die because have a really bad century and
Right? we make no progress.
yes but hey we got that far so Now, I mean, that would be bad,
itself. tBut also it turns out thatf
argument doesn't even work
slow down. because it turns out that we can
fix half the damage in order to get to robust human rejuvenation
in the first place. But the second time around 20
years later we're not fixing
this scenario we're only fixing a third of it and the third time
around another 20 years later we're only fixing a quarter of
what we couldn't fix previously and so on.
And as you can see that's still good enough.
The people are still staying
frailty threshold. nice and healthily above the
gets easier with time. So it gets easier, it actually
extraordinarily difficult to And that means that it's really
that -- rejuvenation therapy is giving a few decades of extra
life will, in fact, give an indefinite degree of extra life
as a result of the rate of
And you want to believe that subsequent progress.
Now here's a vintage car. It's not 50 years old it's well
over a hundred years old taking part in a London rally which is
an annual car rally.
year. And this car, of course, is
getting a lot of maintenance, no
But the critical point is it's question.
more sophisticated maintenance getting no more maintenance, no
years ago when it was only 3 or t4 times old as it was designed
to be.
velocity for cars is already In other words, longevity escape
We're not having to, you know, negligible.
So I'm just going to complete with a couple of minutes on the
Methuselah Foundation.
run. This is the foundation that I
of Cambridge but I quit because II was able to get paid to doy
this stuff full time. And basically what we are --
we're a 501 charity based and registered in Virginia.
And we promote and fund, sponsor
talking about. the hastening of just what I'm
we had no money whatsoever. WhenAnd that didn't stop us.003
We decided that we would get
enthusiasm going raise the stuck in and get public
research in a legitimate, you know, respectable way that
didn't in any way demean it and so we launched the prize called
the Methuselah Mass Prize, as we
We call it the M prize now. It's simply -- we offer you
money if you can get, if you can
any mouse had lived before. make miVery simple idea.ger than
Gets the message across to
talk about science to them for people who go to sleep when you
And, you know, it really worked. more than 10 seconds.
And we didn't have to spend very It got the word out there.
We only put $5,000 in it in the mbeginning.
And now as you can see it's got quite a lot.
And that's just because of
And people around the world who phave put money in and you cane.
still do it.
a PayPal account can add to that And anyone with a credit card or
The research part is the other part.
When we got the M prize really thing we do.
years ago started funding research directly in just the
same way that any standard
because we're very small -- well funding agency would do accept
have standard grant solicitation still fairly small -- we don't
We just fund stuff that I think pis cool..
Which is fun because I know what's cool.
And we are spending that money
The project that I told you about a moment ago, the
introduction of microbial genes into cells to get rid of stuff
that we can't naturally break down is something that we're
funding at three universities now around the U.
S. in Arizona state, at Rice
Columbia in New York. UniverGoing very nicely.d also
Funding's going up all the time.
They're really committed to all The grouof this.tastic.
They're the best graduate students you could possibly
imagine and the PIs that we're
committed to it so it's a glorious situation from point of
view of the grant administrator,
Also over the past year or two so to speak.
other major really challenging we've been funding one of the
The obviation, rather than components of the sense program.
mitochondria mutations. And again a comparable amount of
funding which again is going up all the time.
We're funding that not in the U.
Because we are a very much a S. this time but in Paris.
We expect to be funding at least global enterprise.
projects in the next few months. three probably more like five
one or two people. Again at the same sort of level
money from? Well our number one donor at the
moment is a guy you may have
cofounder of PayPal and is now heard of Peter Thiel who was the
most successful hedge fund in the world, in terms of its rate
of growth, clarity and capital. He's very good at making money
and he's got a lot of it. But he's got slightly less than
he would otherwise have had because he gave some of it to
me. To fund some of this stuff.
And a lot of what he gave was not straightforward
unconditional but rather as a challenge pledge, in other words
we have to get money from other people in order to extract his
money from him. And we're doing our damnedest to
get that money. Eventually we want to be quite a
lot bigger than what we are now.
half a dozen people at the I've told we we're funding maybe
half dozen or a few more in the momentfoundation itself.ybe a
We'd like to be up around 500.
and funded by the foundation. This is the sort of structure we
expect to have. It will include work like this
around universities around the
stand alone facility in which wespecially the integration of a
multiple different interventions
pursued. into the same mice will be
possible. We hoWe're not there yet.on as
But we're working on it.
of 6-digit level of budget. A yWe're now very much at thert
7-digit level.
fast as we can. AnNext step will be along the as
order of magnitude bigger than
We will set up a standard grant solicitation and administration
and application procedure.
and fund work that I haven't So that we can find out about
And eventually we'll get to the point that I described a moment
ago where we have a stand alone facility as well as funding
extramural work.
pitiful amount of money really So we're talking about a pretty
that we'd like to solve. given the scale of the problem
drop in the ocean of biomedical We're talresearch.t really a
The reason we're talking about
because all the work I've sdescribed to you here is works
that we want to do in the next
ten years on mice. several years up to a maximum of
what I like to call robust mass rejuvenation where we can take
middle aged mice and seriously
serious money will be needed in posorder to translate that the
technology to humans. But that's the easy part.
Because after we get sufficient proof of concept that the
gerontological community in general are saying yes, it's
only a matter of time before we do it for humans, then Oprah
will be up there saying let's do
And then -- [LAUGHTER] Money it.
It will be impossible to get will be no object.
commitment to fund this. elected except on a manifested
shortest but the relatively short term, relatively cheap
order of nine digit funding to
the laboratory in mice. get toAnd I'll stop there.pt in
Thank you.
I imagine there's a few minutes for questions if
anyone's got any. >> What will the benefit to
society be of extending life? >> Aging is really bad for
people. It doesn't just kill people.
It kills people really horribly.
We generally agree among It causes suffering.
right? ourselves that suffering is bad,
You know, most people feel this. God said so.
considered to be a bad thing. You know, we are actually
suppose to regard old people as people too.
So, you know, putting two and two together we have a moral
obligation to do this.
of restructuring of society that And yes, there will be a degree
Just as there was with the will be required after results.
I don't know many people who industrial revolution.
pre-industrial world and the would like to go back to the
vaccines and so on when 40% of world before we had hygiene and
one. infants died before the age of
but get over it. Progress does cause upheavals
And progress that alleviates Progress is progress.
progress. >> I have two questions for you.
One is do you practice caloric
If not, why not? restriction?
I don't and there are two >>reasons..
First of all I already look as
frivolous point. though I do and that's not a
who might find calorie I have a feeling that the people
precisely the people who will get the least benefit from it.
However, that's a detailed point
you want. wThe other reason I don't do it
is because I don't think it's going to do anyone much good.
I published something on this a few years ago.
But essentially my reasoning is that the -- even though we --
all organisms seem to have
respond to nutrient deprivation by hunkering down to one degree
or another. The shorter lived you are the
more impressive the metabolic acrobatics is that occurs in
response to nutrient
For example, worms and flies can deprivation.
they normally would if they're live several times as long as
their development. starved at the right time of
live 40 or 50% as long. Now there is good evolutionary
reasoning to suggest that this
That actually the only reason we is actually not surprising.
extent that they're useful. And long famine much longer than
a year just don't happen often
pressure to retain the ability enough to apply enough selective
Second question then is of to survive them.
people have that are posing the greatest resistance or barrier
to you, what are they that are
blocking them from buying into really preventing them or
And by buying into, I mean your vision?
So, first of all, let's get lthe wealthy people out of way.
because the problem the wealthy people don't deserve all the
blame for not getting me money. Because they're just members of
the general public. And they, too, have the
misfortune to have televisions
right message and so on. on which they don't receive the
problem. So, you know, it's a social
wealthy people not being It's not a problem just of
Basically, it's the same problem sufficiently visionary.
scathing answer to the previous like when question.ve a fairly
Nobody clapped. You've all got this problem,
right?
trance. IPeople have made their peaceg
with aging. Aging is something that we've
had to live with all our lives. All civilization's life, so to
speak.
away is because until now, And the reason we rationalize it
It's been this grim thing that's that's been our only option.
not going to happen to you for going to happen to you and it's
there's nothing you can do about quite a long time, okay, but
Then what's your choice? it.
know, obsessing about it and not You can spend your life, you
you can put it out of your mind and get on with your miserably
short life, you know, and make
And obviously that's the thing the best of it.
And given that that's the thing to do, it doesn't matter how
irrational your rationalization is.
Okay, so the people are very
believing and swallowing good at and coming up with and
about aging and, you know, irrational rationalizations
applied the faintest sense of proportion to the problem they
would not dream of considering
So what I spend my time doing is to be arguments against this.
degrees of aggressiveness, essentially, well, to varying
people to grow up and take this problem as seriously as they
would take any other problem. >> I have two questions, as
well. My first question is do you
think your anti-aging technology
ecological solutions to wibasically deal with the factth
that humanity is beginning to reach -- well, it will
eventually reach carrying capacity.
It's whether the ecological -- societal, you know, whether
we as society will keep pace
So the anti-aging stuff will with the anti-aging stuff.
soon will it happen and we will happen be able to cope. is how
A large part of why I'm fairly
because I need -- I feel a need, strident about these things is
technology but also to hasten not the anticipation of the the
technology so that there's a
planning that goes on and we certain amount of forward
when suddenly people announce dthat they've made these mice.d
It seems to me that it's
But I don't say that it's going pto be okay immediately.y.
I think that the transition to a
pretty damn turbulent just as post-athe transition to a to be
industrialized world was pretty turbulent.
But that's not the question we
The question we have to ask ourselves is it worth it?
And my second question is given the complexity of the
metabolic processes and the fact
basically inflict various kinds tof damage on the body, how doto
you account for, you know, how
damage and especially -- my main you're going to target that very
How are you going to, for example, target a decreased
cognitive abilities into old
So first question is why do we have decreased cognitive
abilities with old age in the first place?
And the biggest reason I think
things that I put up on the screen, the fact that the brain
accumulates crap. Inside cells and outside cells
get in the way and stop neurons from communicating so well with
each other and from working so
And a more advanced rate they'll well.
they, therefore, can't do much die at an accelerating rate and
So we're fixing those -- we're when they're dead.
Now that's almost certainly not the whole story with regard to
cognitive decline.
Number one is -- and the biggest There are two other things.
because there are too many one -- is we don't learn so well
It's often -- you know, people distractions.
psychological studies on what people can remember in their
lives.
phenomenon which they've given And they found that there is a
reminiscence bump. the wonderful name to the
however how old, whether you are Basically what this says is that
time of your life that you're going to remember best is your
adolescence.
an equilibrium. AnAnd if you think about it,of
that's not surprising.
age are probably forgetting Evethings as fast as they aredle
learning new things because the process of recalling a
recollection -- a memory -- reinforces it.
So you basically remember the interesting things -- a lot of
which happened during adolescence -- rather well, more
or less indefinitely. Whereas, the things that were
not so interesting tend to be the ones that are forgotten.
That's fine.
then it continues to be fine. If itIn the blue T-shirt.nd 80
The process which you are working on, is it going to be a
completely experimental stimulus
I can't hear. >> What kind of a treatment are
you working on would it be just external stimulus to the body or
would it require conscious
Certainly it's clear that having a good frame of mind, you
know, especially being able to
for longevity. cope well with stress, is good
that. However, these therapies willd
certainly be straightforward
If, for whatever reason, you're aging faster than average,
either because you haven't got
you smoke or because you really like Big Macs, or whatever, you
know, that's going to be fine.
therapies is that the only But the thing about rejuvenation
aging a bit faster or a bit slower is the frequency at which
the therapies need to be
The same therapy should work applied.
I think that answers your oquestion..
( inaudible ) >> So what?
A conscious effort
You got to go to the hospital or whatever, you know, it's not
going to happen in your sleep.
down and rejuvenate them by force, if that's what you mean.
How would you solve the problem of space?
Clearly the birth rate and
less match. the deatThat's clear.o more or
So if we're lowering the death
very widely then we will end up lowering the birth rate as well.
How will we do it?
I have no idea. But I do know that first of all
it's not for us to ask. We have the duty, a moral duty
-- a very clear moral obligation
soon as possible so that to develop these therapies as
choice between the high death rate that we have today and the
low birth rate. And that may be a dilemma but a
dilemma that they are entitled
rather than have us impose these to choose between for themselves
know, you got to have the high values on them by saying, you
That's the first thing. Second thing is if we look, you
know, pragmatically at the what the problem really is and how
bad it is -- well, first of all,
population, the fertility rate let's remember that the
whole developed world and indeed is already plummeting across the
China and India are fine the pre-developed world.
And that's going to continue. Furthermore, there's a good
reason to believe that it may accelerate.
In the west, we see that not
children but they are having only are women having fewer
And that's very interesting because we have to ask why are
they having them later? And of course there are
different reasons for different individuals but the point is
they are, for whatever reason,
their lives until the mid '30s choosing to do other stuff with
Then why are they having the or whatever.
Answer of course, it's then or children then?
Right? never.
That's one thing we're going to It won't be tfix.way anymore.
So if you know you're going to
child safely, you know, at the be perfectly capable of having a
choose to postpone your birth agfor a bit longer if you'rel
enjoying yourself at age 30 and 40 and 50.
And that won't happen really
the resulting from the death early on in the process before
So if you look at the actual rate being low, right?
trajectory is a really powerful math of tinfluence.mographic
Red T-shirt.
how this would adversely effect >society and how these changesof
come about, isn't this theory kind of vague as seeing how the
effects improves your life or effects one person but adversely
effects many or could?
thinking about? >> Who( inaudible )erson you're
But everyone is yourself. It's going to benefit everybody.
The question is are the benefits
the social dangers? >> What about people that have
to change their life and don't
They don't have to. Okay, consider the Amish.
The Amish are a perfectly respectable, stable community
that reject a bunch of existing modern technology.
Now, that's fine. We don't resent them for it,
they don't resent us for it.
It may very well be in the We get along.
society choose to stay where future that some sections of
and others sections choose to go they are and not to go this way
And that's fine too. this way.
overpopulation or whatever let's What's not fine is to say today
values and make everyone Amish not go there let's impose our
That's not fair. in the future.
The first you showed for the Go on.
kind of like you mentioned about therapies where you have this
therapy to like reach half of the one third and like that.
But I'm kind of curious what I
more or less having the same could see is that like you're
recovery rate need to do each atime because the pink curve ise
exponentially decreasing so it
time you have applied a therapy there person you're actually not
decreasing -- >> If you think it through
that's what you would expect. This is the limit.
This is the slowest that you
the frailty threshold. could get and still stay above
that each time you're knocking Because what's happening here is
amount of damage that you're not off the a certain chuck of the
So the rate at which the overall repairing, right?
is slower than it was previously amount of damage is increasing
damage that are increasing. So each of these lines has -- is
increasingly closer to
have to do less each 20 years. horizontal and so you expect to
So the damage is not the It's what you would except.
Yes, that's right. orange line but the blue line?
The reserve, the Y axis, is the amount of damage that you can
afford to accumulate before frailty happens.
So, yes, each of the blue lines is the trajectory of how much
damage you have or equivalently how much reserve you have left.
And the orange line is the
happening. individual, you know, what's
particular individual, how much Sdamage they actually have.a
And the blue lines are the
the therapy doesn't yet repair. So back here, for example, okay,
this chunk of damage here could be repaired but none of this
could.
notional at that point. ABut down here they become lesst
notional because -- yep?
something new if like you can? >> Like have you taken has
I think that-- ( inaudible )
something that I used to, I guess, misjudge in terms of
people's reception of the whole thing.
It's perfectly clear to me that the hardest part of all of this
is going those first 40 years.
That's really tough. Going to this point.
chance of going there within And I think we got a 50/50
But I think we've got at least a maybe 30 years.
a hundred years if we just hit a 10% chance of not going there in
What I'm much, much more certain lot of problems.
here this is going to happen. We're going to have no trouble
staying ahead of the longevity
I think that answered your escape velocity.
In the back. question.
would assess fixing or >> I was just wondering how you
occurs -- the quote-unquote damage that occurs with every
replication.
yeah, okay. So this is something that I've
published on but it's pretty
people don't agree with me on this but I reckon my logic is
pretty sound. There are a bunch of things that
can happen to a cell when it
One thing that can happen is accumulates mutations.
Okay? We've got a solution to that.
Stem cell therapy.
Another thing is that it can get Cell loss right?
to die. into a stateOkay?e can refuses
So the immune system has this problem.
You accumulate cells that are not doing anything.
They won't proliferate when they
and they get in the way they should but they also won't die
other cells. inhibit the proliferation of
is that it will die quite easily The third thing that can happen
really easily. but it will also proliferate
Uncontrollably. Now it may surprise you to learn
that I think cancer is a really good thing.
It's a really good news that we get cancer.
Here's why. Cancer is so bad that just one
cell going wrong can kill us
order like ten or 20 years fairly quickly in a fairly short
Anything else that goes wrong in later.
cells in order to matter. Now that means that the problem,
the main problem that evolution has had in getting us to live as
long as we do is cancer.
aging closely, we find that a lot of the aspects of aging are
side effects of making sure that
younger than we do. In particular, the accumulation
of mutations in the genome that have nothing to do with the cell
cycle, is constrained, in terms of its race, simply by the fact
that DNA repair and maintenance has to be incredibly good in
order to stop us from dying of
So actually cancer is an cancer at the age of four.
It has forced evolution to make a DNA repairing machinery
unnecessarily good for other
In other words, if we can just purposes.
we're done. The other mutations are going to
accumulate but they're not going
until we're a lot older than we tocan ever get at the moment.gy
So, yes, we're going to have to fix that in order to maintain
longevity escape velocity in the
the curve. long run but we're talking off
That's my view. >> Are there any types of damage
that we'll never be able to repair and does that imply that
as life span increases we're
synthetic or artificial technologies organs, bones and
teeth.
structure of your question, because I think that what you
call synthetic or non-biological
the biological ones. technologies sort of blend into
will almost certainly reach longevity escape velocity and
robust human rejuvenation in
almost overwhelmingly by using these first few decades in fact
biomedical approaches to this. straightforward biotechnology,
increasingly we will use But I also think that
We already use them for some non-biological approaches.
implants, you know, things like things of that.e, cochlear
I think that as a non-biological
more and more things, more and sophistication improves that
become easier to tackle by more problems of aging will
biological solutions. nonSo I think there will be a by
continuum and eventually we'll
we'll be using a lot of gnon-biological solutions.,
Is the slope on this curve -- exclusive of science and
exclusive of technology -- is the slope on that curve
dependent on money more than
robust regeneration? anything else today to reach
I think at this point, you know, >> Yes, it is.
that's useful. lots of research is happening
progress is zero. So it'Certainly not. that
Lots of stuff is happening in stem cells, for example.
But most of the seven -- that I'm talking about are definitely
not proceeding as fast as they
more appropriately directed could if peofunding.f there were
There are in each case really,
scientists who work in this ygeneral space and who have alls
the expertise necessary and who are interested in working on
these particular things but they
things are easier to fund or don't work on them because other
and, you know, the sort of easier to get publications for
have to prioritize. thinThat why I started thed to
Methuselah Foundation because with a bit of change, I can --
with a bit of money I can change
I used to give up somewhat slip and slide that said scientists
will do anything interesting for
And that's more or less true. Certainly, I mean, I'm well
integrated into I know
leading scientists in all of personally all of the world
I'm constantly communicating these various fields.
them into doing stuff when I with them and trying to control
course increasingly actually can't pay them as well as now of
So really at this point I've paying them.
than getting enough money sent done all the hard work other
appropriate project. in the direction of the
( inaudible ) >> Specific treatment is going
to change extremely fast. It's going only when these
things come along clearly there's going to be massive
pressure to engage in incremental refinements that do
not simply do this sort of thing
comprehensiveness but also in terms of the
No question about that. However, even at the beginning
when these things are very
foresee any significant delay between the point where they're
available to anyone and the point where they're available to
everybody.
a very unrealistic and That seems, you may think, to be
But here's why. There's going to be this gap
between the point where we get
point where we get these proof of concept in mice and the
That gap is going to be a absolute minimum of ten years
and it's very likely to be 15 or
longer than that. That's a long time for society
to get its head around the whole
And, in particular, it's time for society to have a few
general elections in which it's going to be impossible to get
elected unless you have a manifesto commitment not only to
put enough public money in, as
private money, to get the wresearch done but also to getg
all of training of the medical
and all of the building and factories and so on so that when
the therapies do finally arrive,
made -- the serious money's been the serious decisions have been
This is going to be straightforward for a bunch of
reasons.
matter to people. You know, it's not going to be
the economy stupid in the famous
It's going to matter more. Clinton phrase.
mentality when people are willing to embrace a certain
amount of -- of standard of living in order to end the
slaughter as soon as possible once they actually see it that
way.
economic point of view it's Bugoing to be easy to justify.n
Because being frail is not just risky, it doesn't just kill
people, it's really expensive.
statistic but the average person I don't know if you know the
medical expenses in their last in the west consumes a lot more
of the rest of their life put year of litogether.n the whole
And that's irrespective of how
So we won't have that anymore. old they are when they die.
anymore with these technologies and all that money is going to
be saved. Even at the beginning when these
therapies are very expensive. That expense will be absolutely
dwarfed by the amount we save by
in a grisly state for an extra not having to keep people alive
All right now this is more of an opinionated type of answer.
You can tell I don't like that.
How do you think that the whole psychological process is
going to be different because, I
when they're 25 versus 45. mean, someone thinks differently
I mean, how do you think that's Sgoing to differ..
Well I'm 44.
Okay, so I mean I can see some I was 45 yesterday.
you know, people of my age with regard to how they behave toward
-- in terms of youth and so on. So I, for example, I feel that
in some ways I'm absolutely as
You know, I still enjoy the same much of a child as I ever was.
I still live like a student. sort of informality.
most of modern music. I still listen to stuff that was
from the '60s and '70s and '80s,
So there's plenty of things that right?
alone in society, that are I can see even in myself, let
The question is will that actually be to the extent that
that might be a good thing is it
And to the extent that it might be a bad thing, you know, the
people are sort of old before their time if you like.
Will that go away?
about this. I think that the more health you
have, the more vigor you have,
change to choose to go to discos the more options you have to
want to. with your granddaughter if you
people just don't have at the You know, thmoment.ke that which
So I think there inevitably will
among society with regards the be a greater degree of variety
at given ages but I think that's sorts of people that people are
And equally there will be more fine.
You know, age will matter less. And there's another question.
Yeah, you have one. >> Sort of an evolutionary
ambivalency in terms of how there hasn't been a lot of --
Evolution is a function-- Sorry, aging is a function of
evolutionary neglect, yeah. >> And so in the future as you
proposed, more in terms of
( inaudible ) Do you think that there could be
the potential of evolutionary ambivalency in the other
direction?
Basically evolution of the human >> No.
overwhelmingly under our own race is, at this point, already
We're actually, at the genetic control.
faster now than we ever did before and we're doing sor
because the evolutionary
on the individual genes and pregenetic pathways are beingres
altered by technology, by civilization.
The immune system is a fine example.
A lot of the -- it's pretty much
reasons why people's immune asystems tend to be worse nowe
than they used to be -- and more
is because of the absence of allergies and stuff like that --
infectious diseases. selective pressure imposed by
weak immune system whereas You can get away with having a
having any kids. previously you would die before
accelerated rate especially when So that would happen even in a
able to have good and effective and safe gene therapy.
We will be doing our own
Their own treatments evolution.
Do you think that will be limited at all by own only
intellectual capacity --
That's a pretty ( ihard question.
I think probably not. Simply because we're so good at
enhancing our intellectual
and so on. capacity at all with computers
no predators. >> Wha( inaudible )es that have
You mean why don't they age?
They do of ( inaudible )
longer than organisms that do couhave natural predators. lot
That is the dominant
But it's not the only determinant.
Because even the organisms that have no predators they still
have other causes of death that are not age related.
Things like starvation and
accidents, infections, all these especially hypothermia,
Anything that's extrinsic contributes to the determination
of how much evolution cares about aging.
Is there some sort of, you
pressure for aging that we know, evolutionary sort of
There are still a few gerontologists who look at that.
Who are interested in the possibility that that might be
so. Because there's so much data out
there which in some way looks a bit like, you know, an aging
program.
goes wrong more or less Tsimultaneous, for example, isg
often brought up. But in each of these cases, one
can see that actually is indeed what you expect from the absence
of an aging program.
gerontologist take seriously the But at this point, very few
program. idea that there is an aging
to be a aging program you have Essentially in order for there
aging program would not only to have a model for how the
In other words, how it would evolve but also be retained.
species. actually be a good thing for the
succeeded in finding a model for And people just haven't
( inaudible ) >> Speak up, speak up.
Are these therapies going to
and gray hair? get rid of things like wrinkles
If we can fix the inside than it's going to be pretty damned
easy to fix the outside.
diseases that will be difficult to deal with like auto-immune
diseases. >> There are plenty of diseases
that will be difficult to deal
in the train of events where with but luckily they, the point
these ongoing types of damages, we'the precursors of variousrds
diseases, right.
relationship is very complex and The cause and effect
fact, it probably won't be well indeed known for a while.nd, in
But that's fine.
of damage then by definition If we fix all the various types
function, we are fixing all the consequences of the damage.
So auto immune disease -- well, sure, that's important but what
will they come from?
immune system. They come from inadequacy of the
auto immune problems are age And certainly to the extent that
That people's allergies get worse, for example, then yes,
that will be something that will
the immune system even though that rejuvenation is being done
for more life threatening reasons.
I've exhausted you all. Oh, no I haven't.
One more. >> If you were to fix something,
you need to know what's broken. >> That's not necessarily true.
Carry on. >> Well, how do you propose to
do surveillance in realtime of
able to target different entire organisms in order to be
All right, good question. So the question is -- it's quite
a profound question so I want to
The objection that the make sure everybody heard it.
you know -- in order to fix something you got to know that
it's broken.
thing is in some way -- you know, would be better in some
other way.
You mentioned surveillance of Howthe organism in some way.is?
The thing is we can sidestep all
very simple trick. of our ignorance about that by a
difference between younger All we have to do is look at the
And I don't mean children and really old people here..
I'm talking about, let's say
Now the difference is at the between 25 and 40.
between someone who's 25 and molecular and cellular level
small. someone who's 40 are pretty
still run more or less as fast I mean, I'm 45 now and I can
can still think more or less as as I could wfast. was 25 and I
I'm functionally more or less intact.
But as things stand I've got a
life span and that's of course considerably shorter remaining
made of. got to be a function of what I'm
molecular and cellular level. Now, therefore, if we look at
the composition of an older person and we find differences
and we know differences between that person and a younger person
and we can say if we reverse
to be a good thing. We can't say that if we reverse
some individual difference it's going to be a good thing because
a lot of those individual differences may be adaptations,
may be compensations but they'll
differences. be compensations for other
way it was at a younger age, we Soknow we're going to have thehe
result we want even though we don't know which of the things
were actually bad for us and
I'm all for fixing things that which were not.
All right. might not matter.
The issue of evolution ( inaudible )
Yeah. and>> So if the objective ofon.
evolution, survival of species, it seemed like that there may be
some innate aging mechanism going on that hasn't been
identified and still hasn't been
Because you've got two different identified.
species. possibilities to sustain the
turnover rate, right? OneFaster death rate.her
Or you have a very, very slow turnover rate.
Either of those strategies will result in survival of species
but so far it appears evolutionary from our experience
we're on a high turnover rather than a slow turnover objective.
So that doesn't work. And the reason it doesn't work
is because you're thinking about
that's protected. tYou're thinking about ant
environment in which most organisms die of decrepitude.
Most organisms in the world do
In a typical ecological niche in not die of decrepitude.
nearly all organisms die of starvation or hypothermia or
whatever. Okay.
Evolution has to work within
Evolution can't change that. that.
Evolution has -- for a Okay.
going to work on that species to particular species evolution is
that the species has and so on maximize the number of offspring
survive. in order for the species to
context of the mortality rate that's going to happen anyway.
And therefore in the context in the fact that not many organisms
are going to have offspring at
all going to be dead from other the agcauses than aging.ey're
So that's why aging doesn't matter at those ages.
But evolution does not -- the evolutionary pressures are not
restricted to just creatures in the wild.
We're subject to evolutionary pressures --
You're right, and I mentioned that earlier in respect to the
immune system ago.
We age now simply because we But that's very recent.
the wild. Which was actually not very long
ago in evolutionary terms,
So eventually we'll fix it. But yes, at the moment, you're
quite right, at the moment our
environment is imposing evolutionary pressure to live
longer. And for just the same reason
that, you know, if you took a species that lived a very short
life span and you put it in a protected environment the same
pressure would exist. But that pressure has only been
applied very recently and it
it's a very hard job to do. I think we really ought to stop.
I'm desperately thirsty so
questions can follow anyone who wants to ask more
me.