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Further to the article by David Stipp in Scientific American blog, reviewed by me a few days ago...
Further to the article by David Stipp in Scientific American blog, reviewed by me a few days ago...
Drugs that could help people 'to live to 150' could soon be a reality, according to headlines in The Daily Telegraph and the Daily Mail.
The news comes from molecular-level research into the compound resveratrol, which is found in red wine and dark chocolate, and has been shown to increase the activity of proteins called sirtuins.
These proteins are able to increase the lifespan of yeast, worms and flies, and it has been suggested that they may also play a role in human age-related diseases such as Alzheimer's disease.
This laboratory study looked at whether a synthetic version of resveratrol could stimulate the activity of sirtuins to such an extent that it could theoretically improve human life expectancy.
Although the researchers found that these compounds directly activated the sirtuin proteins, it is far too early and optimistic to claim that a pill could be created that would allow people to live to 150.
This study was interested in biological processes in a laboratory, not the development of an anti-ageing pill. No pill has been made to improve life expectancy in humans, and the '150-year' claim seems to have been manufactured by the headline writers. Dreams of a pill that will allow you to live to 150 remain just that: dreams.
Red wine and resveratrol
Red wine only contains tiny amounts of resveratrol. Any hopes that a bottle of red will extend your lifespan are unfounded.
Where did the story come from?
The study was carried out by researchers from Harvard Medical School, the Massachusetts Institute of Technology, the US National Institutes of Health, the pharmaceutical company GlaxoSmithKline, and other institutions in Portugal and Australia.
The research was funded by research organisations throughout the US and Portugal. No funding support was reported for GlaxoSmithKline (GSK), although a GSK company (Sirtris) employs several of the researchers involved in the project, and one author is an inventor on patents licensed to this company.
Patents have also been filed by Harvard Medical School on the tests developed in their study, as well as by Sirtris and another company for some of the compounds tested.
The study was published in the peer-reviewed journal Science.
Headlines proclaiming that a pill has been developed that will help us live to 150 are highly flawed. It is also unclear what evidence these claims are based on, such as the Daily Mail stating that a pill could be "available within five years". Indeed, it is nearly two years since the last time the Mail ran a story on very similar news.
This laboratory research tested whether, and how, a class of compounds can increase the activity of a particular enzyme previously identified as being involved in a range of age-related diseases.
The research did not assess whether these compounds have the same effect when given to humans in a pill, if there is any effect on human disease or lifespan, or whether such a pill would be safe.
Much more research is needed before we know if these compounds could show any effect on human lifespan.
What kind of research was this?
This was a laboratory study that examined the ways that molecules called sirtuin-activating compounds (STACs) may increase the activity of the protein sirtuin-1 (SIRT1).
Previous research has found that activating sirtuin proteins leads to a longer lifespan in yeast, flies and worms. It has been suggested that SIRT1 plays a role in many age-related conditions, including cancer, Alzheimer's disease, and type 2 diabetes.
Researchers report that SIRT1 has been shown to be involved in several processes surrounding these conditions, including controlling DNA repair and natural cell death, insulin secretion and inflammatory pathways, among others.
These findings make it an attractive drug target, as researchers hope that drugs that safely activate this protein could improve human health and extend our lifespan.
Previous research has shown that both synthetic and naturally occurring STACs (including resveratrol) can activate SIRT1 in the laboratory.
However, there has been debate as to whether this activation was a real, direct effect of STACs, or if it was caused by fluorescent chemical compounds called fluorophores, which are used to monitor the effects of STACs during experiments.
Fluorophores are widely used in laboratory research, as they make it easier to measure chemical changes to these proteins. However, they do not occur naturally in the human body and they may change what naturally happens in the reactions being tested.
There is the risk of a kind of biological Heisenberg Uncertainty principle: the act of observation could change the system you are trying to observe. This means that if the STACs cannot really directly activate SIRT1 in the body, and only do so in the laboratory due to the presence of the fluorophores, they would no longer be potential candidates for treating age-related diseases or extending lifespan.
The set of experiments described in the current study were designed to determine whether STACs were able to directly activate SIRT1, and to identify the precise way that such activation occurs.
What did the research involve?
The researchers carried out a series of complex laboratory experiments to determine whether a range of STACs were able to activate SIRT1. They developed a new way of measuring SIRT1 activation that did not require the use of fluorophores, so that these compounds could not affect the reactions.
The SIRT1 protein acts by modifying a range of different proteins, and the researchers tested whether the STACs enhanced the effect of SIRT1 across this range of proteins, or only on certain proteins. They also assessed how STACs might be having this effect.
What were the basic results?
The researchers found that STACs could activate SIRT1 in the laboratory, even if fluorophores weren't present.
They found that this increase in SIRT1 activity only affected proteins that had a specific type of amino acid in a particular position in the protein.
They found similar findings for all of the 118 STACs tested, including resveratrol.
How did the researchers interpret the results?
The researchers felt that their results meant that a range of STAC compounds can activate SIRT1, and that this process "remains a viable therapeutic intervention strategy for many diseases associated with ageing".
Conclusion
As yet, there is no pill that allows us to live to 150 years old. The research these claims are based on actually aimed to resolve debate about whether STACs, such as the resveratrol found in red wine, can activate the ageing- and disease-related SIRT1 protein. The results suggest that these compounds do in fact directly activate this protein.
Compounds that can activate the SIRT1 protein are of great interest to longevity researchers. This is because they have found that activating similar sirtuin proteins in yeast, flies and worms extends their lifespan. It remains to be seen whether or not producing these compounds can increase the human lifespan.
Researchers have pointed out that the amount of resveratrol in red wine is significantly lower than the amounts fed to mice in previous research. The lead researcher said that, "at least 100 glasses [of red wine] would be needed each day to get the levels shown to improve health in mice". Research is also being conducted into similar synthetic chemicals, as some of these seem to have greater effects in the laboratory.
This type of study is a necessary and useful early step in the development of drugs. On its own, however, it is certainly not sufficient evidence for us to be able to say that STAC compounds can reverse human ageing or help us live for 150 years.
Media claims that such a pill is five years around the corner are ludicrously optimistic. While researchers suggest that pre-clinical studies in mice have been initiated, these studies would need to prove effective and safe, and then be followed by furtherrandomised control trials in humans.
It is important to note that the media coverage of this research failed to highlight the fact that the best way to reap the benefits of sirtuins is to take regular exercise.
Rather than waiting for scientists to develop a wonder drug, why not go for a walk in your local park, go for a swim or have a leisurely bike ride? Read more about the importance of exercise for older adults.
Links to the headlines
Pill to live to 150. The Daily Telegraph, March 10 2013
New drug being developed using compound found in red wine 'could help humans live until they are 150'. Daily Mail, March 10 2013
Cheers! Red wine pills will beat killer diseases. Daily Express, March 8 2013
Links to the science
Hubbard BP, Gomes A, Dai H, et al. Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators. Science. Published online March 8 2013
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