A Cure for Ageing?: David Sinclair at TEDxSydney


Translator: David Hsu
Reviewer: Denise RQ I believe that we’re all only given
one precious life. For those of us who are
really lucky to be born, it’s a life to be embraced, a life to be used for good, and a life that’s worth
prolonging in good health. When we’re all very young, we assume that our parents,
and our grandparents, all our loved ones will be around forever; but then we learn that that’s not true. I clearly remember my daughter Madeleine – here she is –
when she was four years old. I was putting her to bed, and she said, “Daddy, will you always be
around to protect me?” Man, it almost brings a tear
to my eye right now: I think anyone who’s been a parent
knows how this feels. And I said to her
– I had to be honest – I said, “I’m sorry. One day, like everybody,
I will grow old, and I will die.” I watched her eyes well up,
and she gave me a really big hug. But then I told her
– I think what we all tell our children which is, “Just don’t think about it,” and so she did. (Laughter) But here’s my big idea:
I think we’ve all done this in our lives, we all try to forget about this truth. Ironically, I believe
this is preventing us from realizing the lives
we could actually live. My grandmother Vera, she’s an amazing lady: she saved lives in World War II; she escaped persecution from Hungary
and fled to Australia; she had a wonderful sense
of humor, a love of life; and she spent a lot of time raising me; and she never wanted me
to call her grandma – only Vera – because she hated
the idea of growing old. But since then, I’ve watched her grow old. She has watched herself grow old too,
and she used to apologize to me for it. A few months ago, I heard that she fell over in her apartment,
and she broke the top of her femur. She went straight to hospital. They operated on her. Her heart stopped in the operation. I arrived in Sydney with my son Ben,
five years old, to say goodbye to her. She was there, just a shell
of the woman she once was. She had a feeding tube
coming out her nose. She barely knew who anybody was. And I thought, “This thing we call aging –
why aren’t we up in arms about it?” (Laughter) And this once vibrant woman,
reduced to this; it’s incredible. This is just my story, but this is being played out
every day in everybody’s family. It’s certainly not an isolated case. In fact, I don’t want to be a downer, but this, or something like it
is going to happen to all our loved ones, including all of us. That’s actually the best case scenario. So why aren’t we doing more about it? I think we all know
that aging’s important. For example, the World Health Organization
recently put out a report, a 32-page report saying that aging is one of the biggest
problems of our generation. Unless we do something to keep
the elderly healthy and productive, the cost is going to crush
national infrastructures. Our way of life, our economies
are going to fall. This is what the governments are saying. But what you may not realize is a fraction of just 1% of medical research is devoted to understanding why we age, and even less is devoted
to trying to do something about it. And this, to me, is a major puzzle. What I think is going on is
that we just don’t like to think about it. It’s really quite weird. I noticed many of you chuckled
when I was introduced. I think we’re just ingrained
to really not want to talk about it. We feel uncomfortable, embarrassed talking about extending lifespan
and delaying aging. For many people, it’s even sacrilegious. I once debated the bioethics adviser to
President George W Bush on national radio. His point to the audience, and to me,
was aging is natural. It’s part of the way of life. In fact, it makes life worth living. What a load of bull. (Laughter) Alzheimer’s, heart disease, cancer –
these are natural; and we do everything we can
to prevent and slow these diseases down. Ninety-nine percent of medical research is devoted to trying
to slow down these diseases, which actually, only a fraction
of us actually get; whereas aging,
if we’re lucky, affects all of us. So you might ask, “Why don’t we
just continue what we’re doing? Why don’t we just study
individual diseases?” That’s what we’ve always done.
It seems pretty good. But what you may not know is that the rate of aging is actually decreasing. What I mean by that is that we’ve developed many medicines
that actually can treat part of our body, say our hearts – we’re very good
at keeping our hearts healthy – but our brains still age. So we have ended up with – and just to use
my grandmother as an example – a nation of elderly whose hearts
are working well for example, but their brains
are no longer functioning. And this is a major problem
for a healthcare system. It’s extremely, extremely expensive. What we need are medicines that will keep all of our body parts
working at the same time. If we just fix one part of our body, the problem is some other part
will break down: we are just switching out diseases. I don’t think this is
the right way to go about it. If you look at this graph actually,
this really brings it home. We are always taught that our medicines are making us
healthier for longer. That’s not true. Look at this graph. The amount of time
that we are spending in good health is actually decreasing
in terms of percentage. No wonder healthcare costs are going up. What we need to do, of course,
is to keep us healthier for longer. So, I am not talking about
living for 500 years. I see that sometimes quoted in the press. But what I am talking about is an ability for us to live into our 90s
and our 100s in a healthy way and not like my grandmother who suffers. And many of us will go through this unless we do something
about the root cause of aging. I would argue it is
the greatest problem of our time. Well, let me tell you about the work
that I’ve been doing, a little bit, about how I think we can get
at the root cause of aging. So when I was in my 20s,
I earned a PhD in Sydney, and I headed off to Boston
to a place called MIT to understand why yeast cells, little budding yeast that we use
to make bread and beer, why they grow old – because, I figured, if we couldn’t figure
this out for a yeast cell, we had no hope of understanding
why we grow old. Fortunately, I did. And even though there were critics
of this approach, the critics were even Nobel Prize
winners who told me, “This is not the way to go about aging.
Yeast cells don’t get Grey hair. They don’t get heart disease.
They don’t get cancer. But I ignored them, fortunately. I was quite naive, luckily. And in the next few years,
what we discovered as a group was that yeast cells do,
in fact, grow old. and one of the reasons is that their genes start
to switch on as they get older. So what I mean by that is that– Every cell has a set number of genes;
we all know that. In every one of your cells:
the same number of genes, but they aren’t all switched on
at the same time. They need to be kept on and off and tell what type of cell is in the liver
and what type of cell is in the brain. What we found was these yeast cells
as they got older, after about a week, all the genes started
to come on, and they died. Now we could find genes that could actually slow
that process down. We could find genes that could switch off
those rogue genes and silence them. This led to a discovery
of a longevity gene called Sir2. Sir2 stands for
Silent Information Regulator 2. So in 1999, we started a new lab
at Harvard Medical School. I was 29 and figured
I could change the world. It was really exciting. We soon discovered that there are seven
of these longevity genes in our bodies. We call these the sirtuins. So the sirtuins have risen
to scientific prominence. There’re thousands of papers on these now. What we’ve learned is that they seem to protect
our body against diseases of aging. For example, If you put
extra copies of these genes into yeast, little nematode worms,
flies, and mice – they do a lot better. In fact, in most cases,
they live longer in a healthy state. So what we need to do
is to figure out ways to tweak these genes,
to make them more active. And, in that way,
we might be able to delay all the diseases we get as we get older, and, possibly, even reverse aging. Let me explain
what the sirtuins do in our body. I have been very fortunate that the TEDx people have helped me
make some videos here. There’s a new idea about aging: and that is that, as we get older, genes are switched on and off
in the wrong way. So when we are young,
there’s a beautiful symphony playing; but as we get older, the instruments, the orchestra starts to play willy-nilly
and screws things up. If we zoom into the cell,
you’ll see a chromosome. If we stretch out the chromosome, that’s the DNA
all twirled up, there in Grey. The pink blobs are proteins
called histones that the DNA is packaged in. Red means the gene is off. The problem during aging is that chemicals come in
and stick to the histones, and turn the genes on, so that’s what the green lights mean. This gene that should be off
in the brain of my grandmother is now coming on, and that’s a terrible thing. If this gene happened to be a gene
that told the liver to be a liver cell, and now it’s on in the brain, you can imagine the problem. And that’s what we think may be
a large part of what happens during aging. This leads to a really
important possibility. We used to think that mutations,
these irreversible changes to our DNA, are what cause aging; but, in fact, if it is this
– what we call an Epigenetic change – that’s reversible. So let me show you how we can reverse it. These sirtuins actually make proteins
that I’m going to show a cartoon of. It’s going to look like a Pac-Man. What the sirtuins proteins
do in our bodies is that they clip off
these chemical groups. And now the gene that was on
in the old person – in green – goes off again. And that’s what the sirtuins are doing
in our bodies right now. They’re stimulated naturally
when we don’t eat and when we exercise. And If we eat a large hamburger,
we shut them down again. This is not good. So what we wanted to do
was to find a way to turn this system on, to find a molecule
that could be taken in a little pill and turn on these sirtuin enzymes, and, thereby, we could clip off
these chemical groups, keep these diseases of aging at bay
and keep the whole body healthy. We might even one day, in theory,
reverse aspects of aging. As I said, I was in Boston and things
were looking really interesting. I started a company
that was based on the discovery that there were molecules
that could activate these enzymes. The one that we found ten years ago
which got a lot of media attention, was from red wine. It’s called resveratrol. And, don’t ask me to say that again –
it’s a hard word, resveratrol. And so resveratrol (Laughter) as you’ve probably heard, is in red wine. Now, the problem with that is that you’d need to drink
about 100 glasses of red wine a day. (Laughter) No, I don’t recommend that. (Laughter) Don’t do that. (Laughter) But what we clearly needed
was a drug that would do this. Something that’s more effective,
more potent than resveratrol. This company raised a lot of money, and they set to find molecules
that were even better than resveratrol. They found ones that were 100 times
more potent than the red wine molecule. They put them into animals. And these animals – I’m talking
about mice – were much healthier. They didn’t get heart disease. They were protected against Alzheimer’s.
They were protected against cancer. It was extremely exciting. They even started human trials,
and the molecules appeared safe. And there were already hints,
just little hints, that actually these molecules were working
the same way as resveratrol was working to prevent these diseases of aging. So at that point, everything looked great. I thought, “The world is going to be
different in my lifetime. We don’t have to worry.
This is going to all work out.” And then the bottom fell out. What happened was, a few years ago, the world’s largest pharmaceutical company
put out a scientific paper that said that all of this science
was wrong, dead wrong – that resveratrol did not work
on these proteins. In fact, another group said
sirtuins have nothing to do with aging. It was a really
depressing time of my life. I had emails from top scientists
sending me condolences. The clinical trials were put on hold. I thought I’d let my lab down.
I thought I’d let Australia down. I thought I’d let the whole world down. And there were days where I really wanted
just to quit being a scientist. But the good news was, the silver lining, was that it forced us in the lab
to go back and really understand how did resveratrol and these other
synthetic drugs actually work. So I pulled together a group of scientists
– there were about 30 of us – and set to work
to understand what was true. And what we’ve discovered is resveratrol really does bind
to that Pac-Man, sticks on the back of it,
and makes it chomp faster. That’s how they all work.
We were surprised. We didn’t realize resveratrol and these drugs all work
the same way, but they do. It was amazing. So the clinical trials
have started up again, and I’m hopeful that one day
– hopefully, not in a too distant future – there will be medicines
that we can take, say a little pill – I’ve got an example
of what it might look like – we might take one of these with breakfast, and that could ward off the diseases
of aging until much later and keep us healthier and functioning. I really look forward to a day
when this happens, and when it does, I believe we’re going
to look back at today, like we do people from a 100 years ago when people would die
from an infected splinter, which in those days, as you might recall,
was perfectly natural. I’m not only going to believe we have
a right to use this new technology to help ourselves and our loved ones; I believe we have a duty,
a financial and an ethical one. And if you don’t believe me,
just ask any four-year-old. (Laughter) Thank you very much. (Applause)

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