[Applause]>>Okay, so the first thing
to say is, thanks for coming and spending your lunch time
here to listen to me tell you about how eating will
make you live shorter. So I thought I’d start by
introducing you to this man, Dave Fisher [phonetic]. So, he’s a for all intents and
purposes, fairly regular guy. He’s 5 foot 10. He lives in Berkshire
[phonetic], but he has a particular
peculiarity about the way he is. And that is, he practice
extreme calorie restriction. So for breakfast, he doesn’t
eat anything, for lunch he eats about 500 calories,
and for dinner he eats about 1000 calories for dinner. And that’s– that 1500
calories is about two thirds of what the NHS recommends
for the average male. And this has significant
physiological processes– verging on underweight
by his BMI, he’s only 6 percent body
fat which is about the level of a professional athlete. And you’ll be pleased to
know that when you do this for a long period of time, at least after the
first five years, you’re no longer [inaudible]. So why is he doing this? Why all of this suffering
and effort to– and this physiological cost. Well he and thousands
of other people who exercise calorie
restriction believe that this will add an extra 30
to 40 years of healthy life to. So I thought it would
be interesting to look at what the evidence actually is
for this, from the experiments that have been done, and
what we know now from this and what we’re doing
in my lab to understand about the interaction
between diet and aging. So I work here in this
building, in the Institute of Healthy Aging, which is on
the 3rd floor in the Darwin. And we look for any genetic
environmental intervention that will extend healthy
lifespan and we try and do this to improve old age
life for older people. But we don’t work with
humans in the lab, so we work with model organisms
and there are numerous reasons for doing this, one is they’re
relatively cheap to work with. They’ve got good genetic
reagents and they are easy to manipulate in the lab. But from the point of view–
from our point of view, more importantly, they’re
relatively short lived. So we have labs working with
the nematode worms, C. elegans, this is a soil-dwelling worm
that eats bacteria and it lives for about two to three weeks. My lab and other labs upstairs
work with the fruitfly, Drosophila and these lives
for about three to four months and then we have labs that work
with mice and mouse tissues and these guys live for
about three to four years. And so we hope to learn
something about human aging by trying to intervene with
the short-lived model organisms and if we test the same
thing on all three of them, we think we might have something
that’s evolutionary conserved and it might be relevant
for humans aging as well. So I’m sure everyone’s
aware we’re living in an aging society. But I thought I’d perhaps
show you these slides since it tells us two– I think,
very two interesting things that at least I wasn’t so
aware of until a few years ago. So this is the life expectancy
at birth for dozens of nations around the world, so each one of these lines represents
a different country. And so one thing you
can see is that for all of these countries’ life
expectancy at the time of birth has been
increasing overtime. So on the X-axis, we
have the year of birth. But two interesting things. One is, if we draw
a straight line here through the record holding
nation at any one point in time for the last hundred years, you can see that there’s been
a pretty steady linear increase in life expectancy at birth. And if we take the
slope of this line, we can get how quickly this is
happening and it works out that for every 24 hours you
live, we gain an extra five to six hours of extra life. The other interesting
thing is that the slope of this line isn’t showing any
signs of leveling off at all, which means if this trend
continues, half of the children that are born today
should be expected to reach their 100th birthday. And even for someone like me,
who’s– somewhere on their 30s, I’ll be expected to
leave until my 90s. So this is obviously fantastic,
we’re all living longer and more healthier,
but it inevitably leads to these problems, and these
are the diseases that kill us, so the diseases of aging. And so, rightly so, there’s an
enormous emphasis on research on focusing on each one of
these diseases in order to come up with a treatment for
each one of these diseases. Now for those of us who work
in aging have put forward that these are all caused by
one common underlying factor and that’s aging itself. And so by understanding and
addressing aging itself, we can potentially understand and massively improve old
age health for all people. So we all know of ways that
you could increase your life expectancy. So, you could decrease risky
behavior, so if you drive, wear a seatbelt or better
still, don’t drive at all. If you smoke, stop smoking. You could take some exercise, this will help increase your
life expectancy and we all know with people who do this, under
the picture of perfect health. This man here is Dick Bavetta. He’s a referee in the professional national
basketball league in America, and he has been for
the last 37 years. This year, he’ll be 74 years old and he’s still an active
referee in the NBA. But the truth of the
matter is that it’s more like this for most people. [laughter] So we know that
the people who are the ones who are living the longest and reaching their 100th
birthdays now have done all the things that they shouldn’t do. They smoke, they drink,
they’re overweight, and in some cases
they’re even obese. And so this tells us
something about the strength of the genetics that we have in forming our life
expectancy outcomes. But first of all, before we
try and understand about how to treat aging, we need to understand what actually
causes aging itself. So I must say there’s
some doubt about this, but probably the most
intuitively attractive idea which is generally accepted
is that we age similarly to most things which is that
we accumulate damage overtime and fall apart. So one way is wear and tear,
mechanical wear and tear, so we all know that as we
get older, our joints go and this could just be
through mechanical wear and tear of time. But also, we live in
an aerobic environment and to metabolize our
food to generate energy, we generate partially reacted
oxygen, which is very reactive and reacts with molecules
inside our cells. And this type of reactive
oxygen species damage could lead to sort of general malfunction
of intracellular components that could escalate
and sort of lead to a catastrophic
failure over time. But the major difference
between us and this car is that we have error
built-in repair mechanisms. And so we could potentially
slow down aging by either changing the
rate of damage accumulation or by changing the
maintenance of the whole system. And this has got enormous
capacity because if we look around in nature, we actually
think there are some organisms that may even be immortal. So on the left here, this is
the so-called immortal jellyfish and on the right,
the marine hydra. And the way people have
studied this is if you go out into the wild and collect
a whole lot of this hydra and bring them back
into the land, presumably you collect a
whole lot of different ages and over time, it’s been
found that there’s no signs of senescence amongst
these animals. So it’s being proposed that
they are immortal, of course, we don’t know that for sure,
but it does at least tell us that extremely high
levels of functionality in multicellular organisms for extremely long periods
of time is possible. But that’s not the case for
all organisms because we know that different animals
have different lifespans. So for instance,
this mouse [phonetic] on the left here lives– has a
sort of intrinsic upper limit to its lifespan of
about three years, this monkey for about 60
years, and on the right, we have a bowheaded whale which apparently can
live for up to 200 years. And so this tells us
a couple of things, one is that genes are involved
in aging and the other is that evolution has shaped
aging, which is odd, right? Because if we think
about evolution, most of us would think
about it as a sort of an optimization process,
so making you better for your environment overtime. So how is it that aging or
evolution could tolerate such a deleterious
trait like aging and they even select for it. Well, the basis of why
this happens is largely down to these two men, Haldane
and Medawar, who are here at UCL in fact, who recognize
the fact that the force of natural selection declines
with age, so that after the age of reproduction, it
virtually comes down to zero. And maybe the best way of
thinking about this is the way in which Haldane recognized
it was, by thinking about it, late onset deleterious disease
like Huntington’s disease. Now, this has a genetic
basis and so it’s passed on from one generation
to the next. But by the time the sufferer
realizes they have the disease, they’ve already passed it
on to the next generation. So you can see how this
deleterious mutation can escape the force of natural selection
by having at a late onset. So maybe aging actually
works in the same way, where effectively we’re passing
on aging to the next generation. A slight variation on this idea
was proposed and formalized by George Williams, who
put forward this idea of what he called
antagonistic pleiotropy. So this is the idea that early
in life, perhaps the genes that cause beneficial effects
early in life are the same genes that cause aging, thereby,
you could generate a system where you actually
select for aging. And the argument goes like this. So this is my nephew,
he’s very young and so there’s a strong
selection pressure for him to reach reproductive
peak and pass on his genes to the next generation. So what if the genes that
cause this enhancement early in life are in fact
the same genes that causes detrimental effect
late in life and ultimately lead to death, then we
have a system– I have an alternative
version of this, if Bryan Cox [phonetic]
doesn’t do it for you. I found this amazing
photo on the web. So what if the genes that actually cause this early
life beneficial effect are the same genes that cause the
detrimental effect late in life. Now you have a system whereby
you select for aging indirectly by selecting for the
early life benefits. And if that’s the case, it means
that we’re all host of genes, whose normal function it
is, is to cause us to age. And so, if that’s the case,
then we should be able to find mutations in genes that
cause animals to live longer. And in fact, this is exactly
what was found, so 25 years ago, now the first single gene
mutation was reported for the nematode worms, C.
elegans which as you can see from this lifespan, basically
doubled lifespan for the worms. And it was in 2001 that people
first discovered the single gene gene mutation in flies that also
extended lifespan, and in fact, these came out of the Institute
for Healthy Aging upstairs which was remarkable because
people thought for a long time that perhaps this worm thing
was just some worm peculiarity. They have an alternative
developmental phase which is effectively
like suspended animation and so perhaps, they were just
recapitulating this effect during adulthood. So when the first single gene
mutation was found in flies, people really started to pay
attention and then a couple of years later, it was also
found that the single mutation that extended lifespan in mice. So there are two very
interesting facts about this, I think, one is that these
mutations conform to that idea of antagonistic pleiotropy. So by mutating the gene, the organisms have a late
life beneficial effect, they live longer. But they pay the
price earlier in life because they’re usually dwarf
and they’re usually subfecund, so they’re low with
fertility as well. The other interesting thing
about it is that all of these– organisms, first
mutations for all of these organisms were
actually found to exist in the same molecular
pathway, and that’s to do with insulin signaling. So this really looks like one of those interventions
that’s evolutionary conserved and therefore, maybe
relevant to human aging. So just in case you don’t know, I thought I’d explain just
quickly what instant signaling is and how it might be involved. So, inside our bodies,
we’re made up of tissues and cells inside of tissues
and on each of our cells, we have various molecular
mechanisms for dealing with food. So when we eat food,
our body needs to tell us we’ve eaten food so
we then take up those nutrients and put them to good use. So, when we eat sugar, our
pancreas secrete insulin that goes in to our
blood stream, and tells peripheral cells
that have insulin receptors that they need to take
up this sugar and put it to some good use, for
instance in growth. So what I’ve been saying is
perhaps by mutating genes that are in this pathway,
we turn down those genes that are related to
growth and somehow set up an alternative state
inside the cells that’s to do with cell preservation and better preserves
the organism for longer. So that’s fine when you’re
dealing with an animal where you can mutate its genes. But we can’t do this
for humans obviously. And so now, we come
back to this idea of how calorie restriction
might be involved in extending lifespan. Because for most of us, there’s
often the equation between sugar in our diets and the
calories in our diets. And so we come back
to the Dave Fisher and his calorie restriction
diet and this was made– well, more prominent,
I guess last year, if any of you saw the BBC
Two program on Horizon about eating less and
living longer and he went through a number of these diets. So from the outright,
calorie restriction diet through various sort of
intense fasts, I guess, through to what finally he
found was the most satisfactory of them all which
is the 5:2 diet. In which you eat normally
for five days and on two days of the week, you
reduce your income, if you’re a girl 500
calories, if you’re boy to 600 calories for
those two days. And if any of my friends
are representing this, I reckon about 20 percent of the people here are probably
even practicing this diet now. But where does this
actually even come from? Why do we think that eating
less might make us live longer? Well, there is some
experimental evidence for this and it mostly goes back to
this paper which was sort of the first recognized
calorie restriction experiment to extend lifespan and
this was published in 1935, in which Clive McCay took
a group of white rats and he split them
between two treatments. One had free access to food
and the others that had access to a limited amount of food that was increased
overtime gradually. So on the top left graph here where you can see there are
two lines that rapidly shoot up on the Y-axis
and then maintained at a high level throughout life. And this represent the
body weight of those groups that were given free
access to food, so they rapidly gained weight and then maintained it
throughout their lives. These other lines that are sort of stepwise increases
throughout life, these are the restricted
animals. So they were given a
limited amount of food that then restricted
their development and when they started
to look like sick, they were given a
little bit more food, and so you could see
the stepwise increase. And the idea was
that if you stretch out their developmental phase
by feeding them less food and then you keep going with that decreased
food throughout life, you stretch out all
the phases of life and perhaps you live longer. And in fact, this is
kind of what he found, is that if you look
at the lifespan curve of the fully-fed animals, you can see they are dying
much more rapidly than those that were on the calorie
restricted treatment. So this is some time ago
now, and since that time, there have been many,
many experiments in many organisms
reporting a positive effect of calorie restriction to extend
lifespan and that’s all the way from single-celled
organisms like yeast through invertebrates,
through lower vertebrates and even into mammals. And most recently, there
have been two reports in the literature at least
that report at least some kind of positive effect on lifespan of calorie restriction
in monkeys. And so I think it’s
pretty easy to spot which one is the
calorie-restricted one, sort of anxious-looking one
on the left and this one on the right to me just looks like a grumpy old
man, to be honest. Anyway, so I guess what’s
going on here is they’re trying to reproduce that
effect that I was talking about with the mutation, whereby
restricting food somehow lowers this signaling pathway into the
cell to increase growth and sets up an alternative
self-protecting state that protects the
organism for longer. And as a side effect of this, we know that we gain
certain other features and those are the features, are things like what
Dave Fisher has. So we know that the
animals gained all of these physiological
changes and this is the sort of thing that Dave had. So, he has decreased body fat,
I’ve told you that already, he has decreasing levels of
circulating hormone called IGF-1 and there was a lot of emphasis
on this in the BBC Two program, he has lowered levels of
glucose in his circulation and he has a lowered BMI. Other calorie restricters
including Dave would report all sorts of other physiological
benefits. So for instance, if you close
your eyes and try and balance on one foot, apparently this
declines rapidly with age and it’s quite a good
knocker of how old you are. So calorie restrictors would
claim that they can do this for longer than someone
for the same age. Some report improved reflexes
for someone of the same age, other improve in– report improved short-term
memory and improved IQ. So some of these things I
don’t think of that impressive because you can practice at
them and get better at them. But other things
like lowered IGF-1 or lowered glucose,
you can’t cheat that. So the critical thing here is
even though you’ve got these features of an organism
that would be longer lived, the key thing is, are these
actually going to cause you to be longer lived, is
it worth the investment? So I thought I’d take a
couple of minutes to go back to the monkey data since this
should be most informative to us. So there are two reports,
as I said, on the effects of calorie restriction
on lifespan in monkeys. On the top left, we have
the age-related survival for the first group of monkeys
and you can see in blue, the blue line, you
can see the animals that have had free access to
food, and in the red line, the animals that were
calorie restricted. And you can see, there’s
quite a separation there so there’re more animals
alive in the restricted group than in the fully-fed
group at the moment. However, this graph doesn’t
contain all of the data. So there are a number
of deaths that occurred through non-aging related
causes and these were things that were reported
by gastric bloat or complications
due to anesthesia. And it’s– that’s fine to
take them out of the data, but it should be that
they occur roughly equally between the two groups so
that when you reinstate them, you should preserve
the difference between the two lifespan curves. But in actual fact, when
you reinstate those tests, you can see on the right that the calorie restriction
group is actually being more dramatically affected by
those non-aging related deaths than the other group. And there’s actually no
significant difference between these two
lines at the moment. Now, there may be some
difference that’s going to [inaudible] from this
point, but that’s kind of a doubtful outcome
in the end. And this is real and
this is important, right, because if you practice
calorie restriction in order to live longer, you
don’t want to know that there’s an increased
chance that you’ll die of something that’s
not aging related through complications due
to surgery for instance. So what about the second report? That’s the first one
that came out in 2009. What about the second one that
came out last year in Nature? Well, here actually, the
data is even more doubtful. So we have a late onset calorie
restriction treatment here on the bottom left. The solid lines represent males
and the dashed lines females. Again, the calorie-restricted
groups in red and the fully fed or the ones with free
access to food are in blue. And so you can see here, there’s
pretty much no difference between the two food treatments
for males or for females and there’s no statistical
difference between them. And when you start the
treatment even earlier in life ’cause this was late
onset calorie restriction, we find that there’s
pretty much no effect again, the same trend again. So we have solid lines for
males, dashed for females. But in this case, the red lines
seem to be below the blue lines if anything indicating
again that at best, there may be no effect in calorie restriction
to extend lifespan. So I guess this raises the
question, what’s going on here? Why if we had all of
these positive reports of calorie restriction
extending lifespan in all of these different organisms
and then when you do it in the monkeys, it doesn’t work. Well, I think there’s kind
of a reporting bias here. So if you change the food
and see a lifespan extension, that’s very easy to report
that in the literature. But if you change the
food and see nothing, you can actually report that
in the literature obviously, unless, you’re working
with monkeys. So if you’re working
with monkeys, everyone knows you’re
doing it and everyone wants to know what the answer is. And so you can’t not
report this lack of effect, and so I think these
points to something. And actually, if you look into
the literature more closely, you’ll find all sorts of small
reports of people saying, “We tried calorie restriction in
our animals and it didn’t work.” And so I think that this
is telling us something about the way that food
interacts with the organism to affect these lifespan
outcomes. And basically it says that
we’re missing something here. And there’s more information than what we have available
to us at the moment. So there are three
kind of obvious things that are put forward
that we’re missing, and there’s probably
more than this. But the three things
that I could think of straight away were
the genes better, our genetic makeup matters. We all know that
different people live for different amounts of
time, like I said earlier, this woman smoking a
400th birthday candle, that his could then interact
to affect the way we respond to the dietary treatment
for lifespan outcomes. The other reason is that
diet is complicated. So if you just look on the
side of a cereal packet, there are dozens of
nutrients and all of them have recommended daily
intake allowances that all of these things could
be important in shaping our lifespan, that calories are
really a convenient way of summarizing food
into one number. So it’s very easy to, you know, watch your calories
and eat a bit less. But it’s not so easy to monitor
all the nutrients in the diet and make sure you get a
proper balance of them that could be beneficial
for longer life. And the third one which is
probably not so important for the organisms that we use
in the lab because we keep them on the very casually controlled
conditions where that we think that they don’t get sick, but
it’s more relevant for humans and probably for the monkeys
as well is that they live in the real world of course. And so, if you are
nourished differently, it alters your ability to
recover from things differently. So it’s well known that if you
are relatively malnourished for certain nutrients,
you’ll find it more difficult to recover from surgery
or from acute illness. And so these things could
also interact with diet to affect lifespan
outcomes in the real world. So if we’re going to
talk about one and three, but I thought I’d just
take a little bit of time to look a bit more
about number two because this is the work we
do in my lab at the moment. And to go there, I
need to introduce you to our model organism. This is the fruitfly, Drosophila
melanogaster on the right here. And the way we do our
experiments is we keep them– I’m not sure– as you can
see in these glass vials and at the bottom of the
vial, we have their food which is just sugar and
yeast in an agar gel. And this relatively
simple setup means that we can easily
manipulate the food and look for interacting effects of dietary balance
on their lifespans. So when we dilute
all the nutrients in the food beyond which– beyond the extent to which they
can compensate by feeding more, we find that they gain an extra
roughly 20 percent lifespan increase which is not
dissimilar from what we find for the other organisms under
those calorie-restricted diets. So the first thing that
we did was you hold the– since there are only two
components to the diet, is just to hold the sugar
constant and vary the yeast and hold the yeast
constant and vary the sugar. And ask which one of
these components is likely to be responsible
for this effect? And we found it was
the yeast component that was critical
for this effect. So yeast for flies provide
all sorts of nutrients, basically supply everything for the flies except the
major calorie component which is the sugar. So they supply protein,
fats, sterile, vitamins, minerals, all sorts of things. And so we divided up these
into different categories and did the same
experiment again. So we just varied one of these
nutrient groups and asked which was responsible
for this lifespan effect. And this was very
clearly shown hat it was in fact the protein
component that was critical. So this is actually now
also known for mice. I know of an unpublished
study in which if you look very carefully,
the high levels of protein in their diet would dramatically
shorten lifespan whereas relatively restricted
levels of protein in their diet were
associated with longer life. And I think this says
something for diets that very heavily
emphasize protein in order to assist weight loss that we
actually don’t know what the long term effects of these are. But from the experimental
model organisms that we use, it seems to be associated
with much shorter lifespans. But protein is actually more
complicated than all that. So this is the food pyramid
and most of you would know that we get our– the majority
of our protein from dairy meat and some vegetable protein. But protein is actually
made up of subcomponents and their subcomponents
are called amino acids. And there are 20 different amino
acids that make up protein. And they can exist in
different proportions relative to each other in
any one protein. So we then started to manipulate
individual amino acids to see if any of these could
recapitulate this lifespan effect that we see with
protein restriction. And what we actually found
was that if you manipulate by reducing just one single
amino acid in the diet, you could actually fully
reproduce this dietary protein restriction effect. And this is also known
for rodents as well that if you manipulate in a very
careful way a single amino acid in the diet, you can reproduce
this longevity outcome seen– normally seen under
calorie restriction. So what’s going on here? Well, there’s a different system
in the cells that responds to amino acids in the diet. So again, we have this
ability to tell our bodies that we have eaten something,
eaten amino acids in this case. And communicate inside the
cell to turn on pathways that are associated with
implementing those nutrients for instance in growth. And this protein that communicates this signal
is the tour signaling pathway. And it turns out that if you
reduce amino acids in the diet, you reduce signaling
potentially through this pathway and maybe this is the reason
why the cell is reprogrammed to preserved better for longer. Now this pathway is
even more interesting because for this
one, we have a drug. And this drug was found in a bacterium that’s
found on Easter Island. And this drug was found to
inhibit the growth of fungus. And when it was discovered what
this drug actually acted on, the drug is called rapamycin,
was found that it acts on a protein inside the cells
which was then called the target of rapamycin, hence
the name TOR. So we now have a drug
that targets the pathway that intervenes between
amino acids and growth inside the cell. So logically, if you feed
the drug to the animals, you should be able to
reproduce the effect and now we have a
drug for aging. And this was in fact reported
a couple of years ago here in the Institute of Healthy
Aging again that the effect of rapamycin– addition
of low doses of rapamycin to flies throughout their life
results in an extended lifespan. And in fact, this is also now
being shown for mice as well. So it seems now that we
have a treatment or a drug that could be associated
with longer life for treating that works in flies and in mice. So I’ve said a lot of treatments
and genetic interventions and dietary interventions
that can extend lifespan, but I haven’t said much about
what’s actually happening at the molecular level to change
the program of the cells if you like into the long-lived form. So I’ve represented
it always like this. You have nutrients. You have some kind
signal to growth. And all I’ve been saying
is that if you block this, your reprogram the cells somehow
to preserve the cell for longer. Now that’s kind of
the level of detail that we actually
have at the moment. That’s about as much as we know. But there were two major
theories about why this happens. One is that actually when
you block growth like this, that’s all you need
to improve health. So growth is great early in life when you’re actually
getting bigger. But perhaps, it’s not so good to have these pathways
activated late in life when you’re no longer
physically expanding, so maybe you just don’t need
growth late in life and in fact, when you turn these
pathways on late in life, they’re bad for the
functioning of the cell. A slight alternative
version of that is the in turning off the pathway
associated with growth, perhaps you trigger an
alternative pathway that’s associated with maintaining
the system better for longer. And so by enhancing
maintenance and repair and by channeling what the
body thinks is scarce nutrients instead of towards growth body
towards maintenance and repair as a side effect of this,
perhaps we live longer. So I guess given the fact
that we know relatively little at this stage there’s
so much more to know about what actually is
going on inside the cells to cause the animals
to live longer. And given all the confusion
about dietary balance, the genetic interaction
with dietary balance to affect lifespan
and the prospects for how this might be relevant
for us in the real world, it really leads us to ask if this guy just
completely wasting his time, has he invested all of his
dietary energy into something that won’t actually work? Well, it’s a little bit
unfair because actually in all the interviews I’ve
read and seen with this man, he’s one of the first to admit that this is an experimental
diet. He’s not guaranteed a
lifespan benefit outcome, but he’s willing to
invest these 20 years now of dietary restriction in
order to gain those benefits. So I thought it might
be worthwhile just at least updating
people on what it is that we actually know before
anyone decides to do this. But– so finally, I
thought I just check and see of how old people actually
thinks he– think he is. So can I get a show of hands? People who think he’s
25 to 34 years old? 35 to 44? 45 to 54? Okay, well it turns
out, he’s actually 55. So I think most people
would agree that even if he is not going
to live longer, at least he looks
better for his age. [laughter] So– [laughs]
So that just leaves me to thank the people in my lab
that actually do the work. And then the funding agencies
and of course, you for coming and listening to my
talk so thank you. [ Applause ]>>We have a few
minutes for questions. Do we have questions here? There’s a mic coming
down to you.>>So with certain
sort of populations around the world being
vegetarian and [inaudible] of protein reduced
diet, is there any kind of real world data
back this up or?>>So there are lots
of books about this. There’s one book that someone
gave me called the “China Diet”. I’m not sure whether
people have read this. You know, it’s very strongly
promoting the fact that the rule of Chinese diet is relatively
low amounts of prot– of meat and a high
emphasis on vegetarianism, as well as daily exercise
and all this sort of stuff is in fact the key to
living longer. So there are various studies
that seem to agree with that. There’s also some
work that’s been done on the Japanese population. You may have heard of
the island of Okinawa and they’ve eaten a
relatively low amount relative to mainland Japanese people and
these people tend to live longer than those on mainland Japan. And when they immigrate
to America, their lifespans dramatically
reduce, so there’s sort of
evidence there. [Inaudible Remark] Yeah. Humans are difficult.>>All right, we have
another down here.>>If it is found eventually
that restricting something, some part of your diet
actually helps you drop dead. But equally, it find– you find that that connection
make your body frailer or more susceptible, do
you think the age old sort of produce compromise would–
could come in where you do a bit of each and get a
good compromise or is it more black and white?>>Nothing is black and white. [laughs] Yeah, I think– so
there are a couple of things. I guess one thing that’s
important about this, if there were a diet that would
really enhance your health with old age, it would be
important that’s reversible. Okay, so it’s important that
if you start late in life that it’s actually beneficial
and there’s a little bit of work from the labs here upstairs that
the dietary restriction effects on the flies at least
is fully reversible. But whether that’s true enough for other organisms,
we don’t know yet. As– So what’s the other part? If it makes you more
frail, if the price–>>You were saying that it
can make more susceptible.>>Okay. [Inaudible
Remark] Yeah.>>Therefore it looked
like so let’s say in terms of the two days and
five days were true–>>Yeah.>>– I know you’re
saying it isn’t necessary. The fact that you
did one day would that be a better compromise
than with the two days?>>Yeah, I can’t really say. I mean, it’s always
possible I guess. I think what’s really important
here is that what we end up doing is we end up
refining these dietary or genetic treatments to the
extent where we can find– try and tease out the
beneficial effects from those detrimental
ones as much we can. And this should then put us
in the best possible position to understand the molecular
processes that are going on here and actually really come up with
an intervention that’s properly targeted towards aging
rather than coming up with these compromises
as well.>>Thank you. We have some questions
at the back there.>>I’ve always believed or heard that men don’t live
as long as women. Is there anything of this
in your research and also, I wonder if the monkeys were
allowed any access to sort of trees or grass or
anything like that and if not, [inaudible] ’cause they
look pretty depressed. [laughter]>>I think you’re right
about the monkeys. They really– I think this
is a pretty hard life living in these experimental setups. So I’m not exactly sure what
the setup was for the monkeys. But I do understand they
had restricted movement, so I don’t know exactly
what the setup was. So I can’t really
answer that one. There is a difference
between males and females in life expectancy. Exactly why that
is, we don’t know. I can tell you– my lab
doesn’t work on this, but there’s some work in the
Partridges [phonetic] lab that is trying to address this
now, at least for the flies.>>Thank you.>>We have another
question here.>>Thank you. I just had a question, I wonder if you’ve got any recent
research you can recommend about carbohydrates as well. I don’t know if you
mentioned that. I came a little bit
late because–>>Yeah.>>– I know a bit
about the carbohydrates from the recent research
about breast cancer and using that to sort of either
prevent it or to–>>So I’m not aware of really
clearly showing the effects of– it depends what you mean. So it levels– so one
of the major problems when we’re discussing
this always is that it’s relative to something. Okay, so one of the
major criticisms is that all you’re doing is
just preventing someone from overeating. So of course, you’re going to make them live
longer, all right? So what we’re talking
about is some kind of peak or optimum diet that
somewhere in the middle of overeating and undereating. Okay, so the exact way that
carbohydrate could work, that’s really difficult
to comment on without controlling all of the other nutrient
balance properly. So I think we still
got a long way to go before we start
singling out single nutrients to say they have this or that
effect on a specific disease. But what I can say
is that these– there’s something weird about these amino
acid restriction diets and I’m not exactly
sure what it is. But I’m also aware of
evidence in my mice at least that if you deprive mice
of a single amino acid for days before surgery that they have a much
improved outcome after surgery. And I don’t understand
why this is, but people think this might
be some activating some stress response pathway
that then enables you to recover much quickly
once you come out of it. So I can’t really comment
on your exact question.>>Thank you.>>I think we’ve got time
for one more question and this gentleman here.>>Not withstanding the
experiments, we are living so much longer than we
used to a hundred years ago and we are the most obese
nation in the Western World, so is that explainable?>>No, and every time– every now and then you
see in this media, right? Being a bit overweight
is actually good for you. And I think there was
one just the other day in the press as well. But I think there’s some
reporting bias again to do with that which can
explain those effects. I think the majority of
the games that we’ve– that we have achieved over the
last hundred years have largely been doing things like just
washing your hands or you know, antibiotics or you know,
these types of things. And so it means that we’re all
living much healthier throughout life up until the point at which
we start experiencing these age-related diseases. And that’s being reflected in where we focus our
research efforts now that we’re much more interested
in those diseases now, you know.>>All right, well thank you for
your questions and I think you’d like to join me in
thanking Dr. Piper for his very interesting
lecture. [ Applause ]