Fasting: Awakening the Rejuvenation from Within | Valter Longo | TEDxEchoPark

Fasting: Awakening the Rejuvenation from Within | Valter Longo | TEDxEchoPark


Translator: Rhonda Jacobs
Reviewer: Peter van de Ven Thank you very much. Thank you very much. So I’ll tell you a little bit about
what we in the lab have been doing, but also some of the exciting things
in the field of gerontology. And first I start by saying that the medical field has really
turned into a Band-aid field, right? So we wait until somebody develops cancer and then we use chemotherapy
or other therapies that do some good and kill cancer cells
but also kill the normal cells. Or with Alzheimer’s, we wait until somebody’s brain
is very damaged beyond repair, and then we put
a Band-aid on it, essentially, and try to keep the person from
progressing further in their dementia, but it doesn’t really do much good. But even if we were able
to be very successful in curing some of these diseases,
I always ask this question, and guess how much longer we will live if we were good enough
to completely cure cancer. What do you think? Twenty years? Twenty-five years? It actually turns out that it’s only
about three or four years, right? And what if we were good enough
to cure cancer, heart disease, stroke and diabetes today? And the answer is about 13 years. And the reason for this is that if one disease doesn’t get you,
something else will. (Laughter) And this is why, instead, if we – In the aging field, we’re really saying, well, why does a mouse get cancer
after one-and-a-half years of life and people never get cancer when
they’re one and a half years old, right? Well, we get it after 40,
after 50, after 60. And the reason for that
is the mouse and the people, we age at a different rate. So the one-and-a-half years for the mouse is equivalent to 40 years for people. So if we were able to delay aging, just half as effectively
as we’ve already done for mice, we would then get
about 30 years of extended life. So treat aging, and most people say,
well, if you’re going to treat aging, we’re going to have all these people
that are going to live longer, they’re going to have Alzheimer’s, they’re going to have
all these bad diseases, so what’s the point? But it turns out that
if you look at some of our work and work of others, and these on the right
are the long-lived organisms. The first one on the left is yeast –
you have a normal-lived one and the dwarf one lives
up to ten times longer than the one on the left. And the flies in the center, same thing –
the small ones live twice as much. And the mice, finally, the small one
lives about 40-50 percent longer. But what’s amazing about these mice is that they get diseases
at a lot lower incidence compared to the regular mice. And the only difference is a single
mutation in the growth hormone receptor, so the little mice are lacking
this growth hormone receptor. So years ago, we knew
that this simple organism, the yeast live longer,
it was very healthy; their DNA was very much protected. And we knew that the mice
also had this record longevity. But even though they lived longer, 50 percent of them
never developed any diseases, compared to the regular mice – only about ten percent of them, or less,
never developed diseases. So we started looking
for people around the world that had the same mutation
and asked the question: Is it possible that people can also
be so protected against aging but also against the age-related diseases? And it turns out that they seem to be so. I started a collaboration
with Jaime Guevara, who’s an endocrinologist who is following
all these people down in Ecuador, and particularly in the Andes mountains
in southern Ecuador, we were able to follow very closely
about 100 of these subjects. And it turns out that
they almost never develop cancer, and in fact, only one in all these years
that I’ve been monitoring – in over 30 years – only one
has died of cancer. And you can see, instead,
in the relatives, you have what you expect, about
22 percent incidence of cancer deaths. And then, when we look at diabetes, even though in Ecuador, the obesity
prevalence is about 12 percent, in these people, these little people
have a prevalence of obesity which is much higher, over 20 percent. And so any endocrinologist
or diabetologist would tell you, these people for sure
are going to have diabetes, and instead, it turns out that instead
of the five percent prevalence – so five out of 100 people
in Ecuador have diabetes, so far in the case of these little people,
none of them have developed diabetes yet. So they’re very much protected, but the field, particularly
starting in the ’90s, we were all confused about
“How do you stay young?” How do you find out about aging,
and how do you regulate aging? If you look around the world and you ask (Laughter) people who have record longevity – this was the oldest lady
in the world at the time, living in Los Angeles. And she felt that by not drinking
and fooling around – that’s how she got to be 115 years of age. (Laughter) And I’m embarrassed to say,
in the next slide, actually, Salvatore Caruso
in southern Italy agrees with her. And so he came up with “No wine,
no smoking and no women” as a motto for longevity. (Laughter) But, of course – (Laughter) (Applause) (Cheers) But Madame Calment of France
obviously disagrees. And not only she disagrees,
but she got the record, right? She made it to
122-and-a-half years of age. And now you’re saying, okay, this shows
that you can do whatever you want. Wrong. Right? And in fact, I just visited there,
and since yesterday, the oldest woman in the world
is an Italian lady, Emma Morano, and everybody says, well, she eats
three eggs a day and steaks, etc., etc. But then when you look deeper, it turns out that a lot of people
in her family live to 100, 102, 103. And that tells you
it’s so difficult to make it to 100; and that tells you the genetic make-up
of these families is such that they’re much, much more likely, potentially hundreds of fold
more likely than everybody else to make it to such an old age, and this is why they can sometimes
do whatever they want – like in her case,
smoking to 117 years of age. And by the way, she quit smoking,
not because of health reasons, obviously, but because she was embarrassed
that she couldn’t light up anymore, (Laughter) and that was her reason
for quitting smoking. You know, a lot of us in the field,
mostly 20 years ago or longer, we started saying, well,
we can never figure out how people age because it’s too complicated,
so let’s turn to very simple systems. And some of us turned to bacteria,
the unicellular baker’s yeast, what’s used to make bread and wine; some people studied worms. But something that I first
had described many years ago was if you starve these organisms, you switch them from a lot of nutrients
to water, they live longer. It’s very counterintuitive – you think
you starve them to death, but no. Not only they didn’t starve,
they lived longer, they were very protected. So that was a very surprising finding
that I had made back in the days at UCLA. And now, decades later, we actually have –
don’t worry about the details here – but we now have a network;
we understand why fasting works. Particularly, fasting works because
amino acids in the proteins of the diet activate one pathway
which is called TOR pathway and another one
called growth hormone IGF-1, and then sugars in the food
activate the second pro-aging pathway, a pathway that accelerates
the aging process called PKA, right? And the other surprising thing
we were wishfully thinking for was that this is conserved, conserved from simple organisms
all the way to humans. It turns out that it probably is. The focus of my talk – we now clearly know
that these pathways, these genes, these [inaudible] genes can protect and make all kinds
of organisms live longer. And fasting can have a major contribution
or orchestrate these genes. But something that happened
in one of the experiments in my lab that Chia-wei Cheng was doing,
which was we fasted mice, and when you fast the mice, they become
very protected against chemotherapy, and all kinds of different toxins, but chemotherapy
is one of the ones we used and are running
a lot of clinical trials on. But the more surprising thing was that even though the mice
were protected from chemotherapy, after six cycles
of fasting and chemotherapy, only in the mice that were fasted
for the six cycles, the white blood cell number
went back to normal. And so that was very strange, and we said, this is not possible by protection;
how can they just go back to normal? And so we started
thinking about regeneration. Is it possible that fasting
is telling the body, “Okay, now I want to make new cells;
I want to regenerate the immune system.” And so I started thinking, well, maybe the body
has everything in it to fix itself, to regenerate and rejuvenate. So I started thinking about
how does a couple of 40-year-olds generate a perfect baby,
a zero-year-old baby, right? And then, if you think about it,
you have old sperm and an old egg, right? And they get together in the same body, and then, all of the sudden,
it just … perfect, right? So then the body knows how to do it, we just – we don’t know
how to make the body do it. So is it possible that fasting
is one of the ways to push the body to do exactly that – go into this regenerative,
rejuvenating mode? And evidence for that comes from the mice. When we took mice
and started at middle age, and give them what we call
“fasting-mimicking diet.” Now that we know how each ingredient
orchestrates this genetic network, we can play with the diet to make mice –
and people, as you’ll see in a second – think that they’re fasting, right? And so with this diet
that we start at middle age, and then we feed it to the mice
twice a month for four days, and then we return them
to their regular diet. And it turns out that you see
the level of white blood cells in the young mice is very high, and then in the old mice
it goes to a very low level. And then on the far right, you see the old mice that have been
on this periodic fasting-mimicking diet. So now the level of white blood cells
is back to the youthful level that they had at four months of age. So you know about the connection
between the immune system and cancer, so one of the things you would expect is the immune system
is getting stronger as I just showed you, and rejuvenated,
the level of tumors goes down, and actually goes down dramatically, so the mice that have
been on the diet periodically have about half of the tumors. But these tumors also occur later, and you see there on the right, the red dots are the mice
that were on the fasting-mimicking diet, and the grey dots are the mice
that are on the regular diet. So a lot less cancer, later in life, and a lot of the tumors
are benign in nature instead of the malignant ones that are developed
by the mice on the regular diet. Okay, so, regeneration from within –
how does that happen? I’ll just summarize it very quickly,
but what happens in these mice is you have these genes that I already
told you about, IGF-1 and PKA, and these genes basically keep
the stem cells in a stalled mode, right? And you have a high level of immune cells,
but a lot of these cells are damaged. This explains a lot of the autoimmunities
that people have, right? So they’re not necessarily functional
or functioning well, especially in older people, so when the mice or people fast, now this stem cell, this IGF-1
and PKA genes are reducing their levels, and now the stem cells are activated,
the hematopoietic stem cells, so the stem cells
of the blood are activated, and actually the immune cell level
goes down, right? So the patient or the mouse
is temporarily immunosuppressed, right? And then, the trick happens
when you re-feed. Now the stem cells
that were activated during the fasting, they go to work, and they start
regenerating new immune cells. So in the mouse it’s really dramatic because the level of immune cells
goes down to about half and then back to the normal level. So within days, the mice are able
to regenerate half of their immune system. And the result of that
is what we call longevity extension, so these mice are now living longer, particularly when you look
at the average survival. Okay, so what about people? We can do this in mice,
but can this be translated to people? And most people think that we can go
maybe ten days without food. It turns out that most people,
most of you, can go for 60 days, right? You can be with no food at all
for two months, right? And actually, like the Emperor penguins
from the South Pole, some people can actually
go for six months with no food at all. We completely forgot this used to be
very common in all kinds of religions, and now slowly, it is disappearing
from all religions. What happens during fasting, the body, first of all, turns
from a glucose, a sugar-burning mode, into a fat-burning mode. And you see there,
those are the ketone bodies, beta-hydroxybutyrate, the blue line,
that is building up. So after just a couple of days
on this fasting, your body completely reprograms. And even your brain, that for most of you, all your life
is being fueled by sugar, is now moving to a fat-based
metabolism, right? This is why people usually get a headache
after they fast for the first time. And so we developed, again,
the mouse fasting-mimicking diet; we developed the human
fasting-mimicking diet. And again, the point of this is to trick
the body into thinking it’s fasting, like in water-only fast. And so we tested this in a group
of 100 subjects at USC, and these people were asked to go on three cycles
of this fasting-mimicking diet, between 800 and 1,100 calories per day,
and the diet lasts for five days, so they were asked to do three of these. So in three months, essentially they did
15 days of this fasting-mimicking diet. And the results, I think, are again, in agreement
with regeneration and rejuvenation, although we can’t prove it in humans yet. But for example, if you see blood glucose, in the normal people
that had normal fasting glucose, it dropped just a little bit
after these three cycles of the diet. But in pre-diabetic, it dropped a lot. So it went from 104 or so to 92,
back to the normal level. And if you look at IGF-1,
one of the key markers, risk factor for cancer, people that have a normal level
of IGF-1 to begin with, it was a small drop. But people that were at risk for cancer,
they had very high levels, it dropped a lot more. And the same thing also
for one of the major risk factors for cardiovascular diseases,
C-reactive protein, it’s an inflammatory marker, and so people that have
high levels of this marker are at risk to develop
cardiovascular diseases, and you see that there is no change
for the people that had good levels of it from the beginning, and a big change for people
that had very high levels of it. The circulating stem cells
in the normal diet, the stem cells in
the body of the patients was low, and then when you fast them,
it goes way up. You know, what happens in life
because of diet, aging, toxins, etc., we accumulate damage, and this damage can lead
to all kinds of diseases. And the fasting-mimicking diet
switches the clock back a little bit by promoting this regeneration,
rejuvenation effect, and now we’re seeing effects that are consistent with protection
against all kinds of diseases, including diabetes, cancer,
cardiovascular diseases and Alzheimer’s. So to summarize, I use my mentor
at UCLA, Roy Walford. And Roy was one of the pioneers
of calorie restriction. He, back in 1990, I think it was, had the bad idea to lock himself up
with another seven people in a place in Arizona called Biosphere 2. So eight of them went inside this place, and then inside of this place,
they became calorie restricted, And when they were calorie restricted,
this is what they looked like. So this is very extreme, right? They went to this very extreme
calorie-restricted diet. But the point I’m trying to make
is about organs. If you look at Roy Walford in the middle,
while he was in the Biosphere 2, his organs had shrunk
to very small levels. Like for example, his liver was probably
about half of the normal size. So half of the size that it was before
he entered Biosphere 2 on the left, right? And then he exits Biosphere 2 – and by the way, I was there
when they came out, and it was a very stressed out
group of people – (Laughter) but you see now, that’s Walford six months
after he exited Biosphere. He went back to the same weight, and the organs, whether it was
the muscle, the heart, the lungs, all the different systems are now
regenerated, back to the normal size. And there’s really not many
other ways to do that, but to turn on stem cells
and regenerate very much in the same way that the zygote and the blastocyst and the cells during embryogenesis
are forming the embryo, so we think that that’s probably
the most powerful way to get this coordinated response, regenerating multiple systems
back to a more youthful state. And I just want to end with my last slide
and with Salvatore Caruso, who, by the way,
was married and had children, so this idea about the women
maybe was a little bit made up. (Laughter) But I think, you know,
the diet helped him a lot, but also a big factor, I think,
for Salvatore was he wanted to live, he wanted to have the record. And he was always looking around
the world, like, “Who’s older than me? How many years I have to live
to make it there?” So it was great. And I’m just going to end with this song. (Guitar music;
Salvatore singing in Italian) Thank you very much. (Applause)