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New class of anti-ageing drugs | Innovations

New class of anti-ageing drugs

New class of anti-ageing drugs

Updated 21 March 2013, 13:38 AEDT

A remarkable discovery that may change the way we think about ageing—forever

PROFESSOR DAVID SINCLAIR : This pill would protect you against maybe twenty other diseases from cancer to heart disease, even type 2 diabetes and Alzheimer’s so this would be a super medicine, one that would be treating one disease but preventing twenty or more others.  

DESLEY BLANCH:  That’s Australian geneticist David Sinclair from Harvard University and the University of New South Wales. He is predicting drugs that combat ageing may be available within five years. 

Their new research has finally proven that a single anti-ageing enzyme in the body can be targeted, with the potential to prevent age-related diseases and extend life spans maybe out to 150 years.

He and his international team have shown that a molecule in red wine can be used to activate an anti-ageing enzyme in people. They say their work ends the dispute over red wine’s anti-ageing properties.

PROFESSOR DAVID SINCLAIR:  Well, we started out not looking at red wine, we were looking at genes that would extend the life span of simple organisms. We even started in baker’s yeast,, little fungus and we found that there were a set of genes, these are called sirtuins, that when you turn them on, organisms are healthier, they live longer. And we were looking for any molecule that we could find that would turn on anti-ageing pathway, And the one that was working the best for us, the natural compound that we found, the best one was resveratrol and I looked up where resveratrol was and fell out of my chair when I saw that was in red wine.

DESLEY BLANCH : And now to the breakthrough. What have you found?

PROFESSOR DAVID SINCLAIR : Well, what we’ve discovered is that the red wine molecule and some newer more potent drugs that we’ve been developing, they stick to this protein that controls ageing and makes it more active and so you can think of this surtuin enzyme as a protector of the body. It tells other proteins how to repair the cell and keep the body healthy, and we’ve found a way to make it more active and make the body healthier we think.

DESLEY BLANCH : Your earlier work has been fiercely contested by other researchers who questioned whether resveratrol was in fact activating this anti-ageing enzyme. So how do you feel today having proven your science?

PROFESSOR DAVID SINCLAIR : Ah, relieved mainly. I have a lot of hope and enthusiasm for the ageing pill and its possibility of having medicines that could revolutionise health and make people live into their 100’s in a healthy way. I’m just happy that the science is back on track, nothing more than that. We still have a long way to go and a lot of work to do.

DESLEY BLANCH : Well, you’ve shown that the enzyme surtuin can be switched on--and you used 117 known drugs and that was out of maybe 4,000 you said so, as well as with a low calorie diet and exercise and the anti-oxidant resveratrol that’s found as you say in red wine and grape skins and peanuts and berries. But you’ve enhanced its behaviour with stronger synthetic activators, which you say means a whole new class of anti-ageing drugs is now viable. So what will it actually mean for cancer and for Alzheimer’s disease and Type 2 diabetes, just to start with?

PROFESSOR DAVID SINCLAIR : The red wine molecule was just a starting point. It really just proved that it’s possible to turn on this anti-ageing protein. And what we’ve been doing really for the last 8 to 10 years is taking that knowledge and making more drug-like molecules, because the molecule in red wine resveratrol, it’s not very available in the body when you drink it, it’s not very potent. So we’ve been steadily improving the molecules so that they are a hundred and some of them are a thousand times more potent at activating this anti-ageing pathway.

So what I’m hopeful is that if we can get some of these molecules through clinical trials and if they prove safe and effective, then cancer patients, Alzheimer’s patients, type 2 diabetics would have a new type of medicine they could take, that wouldn’t just treat one disease, but prevent and treat many, many others.

DESLEY BLANCH : A bit of the history. You believed in this technology to the extent you formed a start-up company, Sirtris in 2005 out of your Harvard laboratory to develop the anti-ageing medical technology which was then subsequently sold to the drug company GlaxoSmithKline in 2008, to which same company you’re now a scientific adviser. So what is GlaxoSmithKline doing with the technology today?

PROFESSOR DAVID SINCLAIR : They’re pushing ahead with the clinical trials which I’m sure everybody knows are extremely expensive and beyond the capabilities of my little academic lab. We’re talking tens, up to 100s of millions of dollars. Eventually it may cost a billion dollars to get one of these drugs approved and so GlaxoSmithKline has the resources and the knowhow that my lab doesn’t, to try these in various diseases of ageing, anything from Type 2 diabetes, even to diseases of inflammation, like arthritis.

DESLEY BLANCH : Well, if your drugs can mimic the benefits of diet and exercise, will there be any impact on weight?

PROFESSOR DAVID SINCLAIR : We were originally thinking that we might make our--the animals in our study are mice--much skinnier, but that didn’t happen. What we found was that the mice still became fat on a Western diet, but what was incredible was when we opened up the mice their internal organs were skinny and when we looked at their health, they were as healthy and, actually they turned out to be just as long lived as the lean skinny healthy mice.

So I don’t think this is necessarily going to turn out to be weight loss pill, but it may protect your insides, even though you’re, if you are obese, then you may live just as long and healthy as someone who’s skinny, and also what we found if you’re already healthy, these molecules like resveratrol, they enhance your health. So it’s not an excuse to sit on a couch and just pop a pill, because you get greater benefits, the healthier you begin.

DESLEY BLANCH : Still looking at that future. Is there any possibility that we could take an oral medication as an anti-ageing preventative or would these drugs be strictly prescribed for certain conditions?

PROFESSOR DAVID SINCLAIR : Well initially I predict that they have to be sold as a medicine. There’s really no approved way for your doctor to prescribe anything but something that’s been tested in clinical trials, so we really do need to make a regular medicine.

But my hope is that once a drug is on the market that, let’s say 10,000 people are taking that drug; we’ll notice that that group of people is in general healthier in many ways, maybe even tends to live longer and so that would be a way to have some evidence that this drug will benefit people more broadly and eventually, I don’t know how long this will take, but I hope there is a time when we can start taking this type of drug in our early 30s and 40s so that we can have the greatest benefit.

DESLEY BLANCH : And it’s not a matter of just having that extra glass of red wine, because the resveratrol within that supply I think you said, was very small, so we’d have to probably drink too much red wine to try and get any positive health gains. They’d be probably negative gains wouldn’t they after all that consumption?

PROFESSOR DAVID SINCLAIR : Oh well, you know, like most people, a glass of red wine occasionally is fine and I think most doctors would agree that for health it’s fine. But to get the sort of disease-fighting amounts you’d need to drink about 100 glasses a day, which, as you said, is something that I wouldn’t recommend.

DESLEY BLANCH : Well, you’ve threatened us of running faster while fatter and living to be maybe 150 years old, and I’m wondering if that’s something we really want, apart from the issues to do with accommodating us and feeding us over this longer period of time. But I guess from the point of view of getting rid of a few diseases, it’s got to be good news!

PROFESSOR DAVID SINCLAIR : Well, that’s really what we’re trying to do here, it’s to make medicines to treat diseases and make people healthier, happier, more productive for longer and I don’t think anyone would be upset if we were able to create medicines that help people.

It’s true if we do end up living a very long time we’ll have to change things but we’ve been doing that for the last hundred years anyway and I think no one would want to return back to the 1920’s, the days when you could die from an infected splinter. So I think it’s all a good thing, but we will have to adapt for sure.

DESLEY BLANCH : So for you David, what’s the next step?

PROFESSOR DAVID SINCLAIR : Oh well, in my lab at Harvard and also at UNSW (University of New South Wales) where I also have a group, we’re looking for even better molecules to delay ageing and treat diseases and we’ve got some pretty interesting discoveries, at least in mice, and then we’re hoping to do some more clinical trials and keep working hard at trying to make the next blockbuster medicine.

DESLEY BLANCH: After the Forever Young Pill, we can only wonder what that next blockbuster medicine might be. That was David Sinclair Professor in the Genetics Department at Harvard University and from the University of New South Wales in Sydney.

Contributors

David Sinclair

Guest

Professor, Genetics Department

Harvard Medical School

and The University of New South Wales

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