David Sinclair
Here is the full transcript of Australian biologist and professor of genetics David Sinclair’s TEDx Talk: A Cure for Ageing? at TEDxSydney conference.
TRANSCRIPT:
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. 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?” 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 – 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 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. No, I don’t recommend that. Don’t do that. 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. Thank you very much.
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