Alzheimer's genetic risk factor linked to resveratrol target protein: Study

New research has identified a link between the major genetic risk factor for Alzheimer's disease and an 'anti-aging protein' targeted by the plant polyphenol resveratrol.

http://www.nutraingredients.com/Research/Alzheimer-s-genetic-risk-factor-linked-to-resveratrol-target-protein-Study

Two studies hail resveratrol type 2 diabetes potential

Supplemental resveratrol should be considered as an adjunct to standard anti-diabetic agents in the treatment of type 2 diabetes, according to two studies conducted at the University of Medical Sciences in Iran and JSS University in India.

 http://www.nutraingredients-usa.com/Research/Two-studies-hail-resveratrol-type-2-diabetes-potential

Evidence-Based Complementary and Alternative Medicine Volume 2013 (2013),

Article ID 851267, 11 pages

http://dx.doi.org/10.1155/2013/851267

Research Article Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients

Conclusion and Summary

The results of this study clearly demonstrate that resveratrol supplementation in the presence of standard antidiabetic medication has major benefits in T2DM patients, which include a pronounced lowering of blood glucose, HbA1c, insulin levels, and insulin resistance, as well as improvement in HDL levels (Figure 2). Unlike earlier reports [21–23] which showed mild effects on hyperglycemia and hyperinsulinemia, our study highlights the marked changes and the potential of resveratrol as an antidiabetic molecule. It is also important to note the beneficial effects of resveratrol observed on metabolic parameters, despite the fact that there was no appreciable effect on body weight or body composition. Some of the observed reductions in HbA1c and HDL with resveratrol supplementation are very significant that they can be compared to benefits achieved with front line antidiabetic drugs. Other important observations which stem from this study are that: (a) 1 g/day of resveratrol supplementation for 45 days had no adverse effects in type 2 diabetic patients and (b) resveratrol not only complemented standard antidiabetic medication but also provided added protection (over standard antidiabetic therapy).

Please read the full article here: http://www.hindawi.com/journals/ecam/2013/851267/

ABC Insights - Staying Alive program

An extraordinary group of older people and researchers discuss how much longer our life spans are now and how much longer they may become.

sbs.com.au - Staying-Alive



Resveratrol is discussed and a healthy life span of up to 120 is mooted.

Here is David Sinclair speaking at the TedX Conference in Sydney - this was linked from the SBS website also.

ABC National Health Report - Feb 4, 2013 - Resveratrol

Professor Finlay Macrae at The Royal Melbourne Hospital is currently leading a trial that aims to investigate the preventative effects of red wine, containing resveratrol, on the development and progression of bowel cancer. Interview with Dr Norman Swan.

Transcript

Norman Swan: Let's stay in the neighbourhood and go to the head—or should it be the bottom—of colorectal medicine at the Royal Melbourne Hospital.

Professor Finlay Macrae is a leading authority on bowel cancer prevention and we've had him on the Health Report before talking about aspirin. He's now starting another prevention trial, this time into a substance called Resveratrol which comes from wine, and which I'd only heard of before in relation to slowing down ageing and life extension.

Finlay Macrae: Yes, there is a literature on that, mostly derived from animal studies and some invitro work.

Norman Swan: What exactly is it?

Finlay Macrae: It's a polyphenolic compound.

Norman Swan: It's also a polysyllabic word. What does it mean?

Finlay Macrae: Well, it's a chemical compound inherent in fruits and particularly grapes, and it's thought to be one of the agents from grapes that has health benefits. Resveratrol is the most prominent phenolic compound in grapes.

Norman Swan: And it's an antioxidant.

Finlay Macrae: Yes, it has antioxidant effects but it has a range of other effects that are perhaps more relevant in that it may have anticarcinogenic effects. For example, it slows down proliferating cells and promotes apoptosis, or programmed cell death, which is one of the body's mechanisms to delete early malignancies developing in the body.

Norman Swan: Essentially the body's cleaning-out process, and some people think that cancer is a failure of that programmed cell death and cells that should have died keep on living.

Finlay Macrae: That's correct.

Norman Swan: And what makes you want to do a trial of this? Has it been studied in other areas and shown promise?

Finlay Macrae: Well, it's been studied a lot invivo, in cell systems, including colon cancer cell lines. It reduces the activity of the COX enzymes which is the mechanism by which aspirin works to protect against cancer as well. And of course there's epidemiological evidence because the polyphenolic compounds of which Resveratrol, as I mentioned, is a predominant one is very much part of the southern Mediterranean diet and we know that the southern Mediterranean diet has a profile of protection against bowel cancer. Resveratrol might be contributing to that southern Mediterranean dietary protective effect.

Norman Swan: So you're planning this trial—what side effects are known from Resveratrol, because nothing is free of side effects.

Finlay Macrae: No, well, it's pretty safe. Of course in drawing the substance from an alcoholic beverage (wine) we've been certainly concerned about that. So we've actually developed a Resveratrol derived from Australian grapes which is de-alcoholised.

Norman Swan: So you can drive and be on this trial.

Finlay Macrae: Yes. And apart from that, it's pretty widely used by the health food industry and has a status of generally safe. So there's not much that we can really pinpoint with respect to risk, although you're quite right in saying there's always some reservation about that with time passing, but it's not as if it's a new compound, it's been used for a long time.

To determine effectiveness for prevention of bowel cancer, and the most solid end-point of course is cancer, and that's perhaps what everybody would think a trial might direct, but that would be a vast trial involving lots of people and millions of dollars.

Norman Swan: So what you're getting to is that you're doing a trial which is not looking at cancer but maybe somewhere along the path to cancer.

Finlay Macrae: Along the line, yes. So adenomas, or benign polyps, are another end-point that's being used quite commonly, but we've taken a step even earlier than that, and what we're looking at is the landscape, the molecular landscape if you like, of the lining of the bowel, to see if we can shift a range of molecular characteristics that we know are associated with either protection or promotion of malignancy. We're looking to shift that into a landscape that is much more protective, with the use of Resveratrol.

Norman Swan: So to keep with the landscape metaphor, you're tilling the soil a little bit and trying to change the chemical composition of the soils, it grows a more healthy tissue surrounding the bowel.

Finlay Macrae: Yes, and in particular a soil which is not associated with or support the development of tumours.

Norman Swan: So people are going to go on to Resveratrol or the placebo. And are you looking for people who are at particular risk of bowel cancer, or just people off the street?

Finlay Macrae: No, we're starting with a group that are already at high risk who have a profile of this landscape which is associated with tumour development, and that would in principle be people who'd had previous polyps or cancers themselves, or people who've got a first-degree relative with bowel cancer. They're our major target groups because they already have a background landscape that lends itself to being protected with an agent such as this. So they're the group: first-degree relatives with bowel cancer or people that have had bowel cancer or polyps themselves.

Norman Swan: How long will you be on the trial?

Finlay Macrae: Six weeks.

Norman Swan: So you're expecting to see those changes, and if you've got those changes how confident would you be that they will result in a lower risk of cancer in the long run?

Finlay Macrae: There's some leap in scientific thinking between changing the landscape and actually reducing the risk of cancer. But the thesis is that if we change the landscape into a protective-looking one, this provides a little bit more evidence, quite important evidence, this is the first evidence in humans that the compound is active in terms of its potential to be anticarcinogenic.

Norman Swan: And at the moment really all people have is aspirin.

Finlay Macrae: Aspirin (we've spoken about that before, Norman, of course) is the lead boy on the block at the moment.

Norman Swan: Or girl…

Finlay Macrae: Or girl, yes. But non-steroidal anti-inflammatory drugs of other types are protective, the usual ones people use for arthritis, a lot of them are protective of various types of those agents.

Norman Swan: If you take aspirin what sort of a reduction in risk do you get? I suppose it depends on the person, but on average?

Finlay Macrae: Fifty per cent.

Norman Swan: So it's a pretty significant reduction. And would you be expecting the same order of magnitude with Resveratrol, or greater?

Finlay Macrae: I think we'd be looking hopefully to get to that sort of effect, 50% reduction.

Norman Swan: So just before we get on to where people can go if they want to take part in this trial…is it only people in Melbourne, or are you looking for people nationally?

Finlay Macrae: No, only in Victoria.

Norman Swan: How do people get in contact with you if they want to take part in the trial, if they fit the bill?

Finlay Macrae: They're best to contact our research team, Virginia or Brooke, on  03 9342 8995 . That's our research office in the Royal Melbourne Hospital.

Norman Swan: And we'll have the email contact on our website. Professor Finlay Macrae is head of colorectal medicine and genetics at the Royal Melbourne Hospital.

 

 

 

Study supports anti-aging effects of red wine ingredient resveratrol

By Carolyn Y. Johnson

 |  Globe Staff  

  March 07, 2013

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Kayana Szymczak for the Boston Globe

Harvard Medical School biologist David Sinclair and more than a dozen colleagues who study ways to slow aging raised a glass of red wine at the restaurant Catalyst in Kendall Square last week -- in a toast to red wine.

It was an early celebration of a study published Thursday, which Sinclair hopes will finally settle a contentious debate that has been running since he showed 10 years ago that a red wine ingredient, resveratrol, lengthened life in yeast.

The influential work immediately captured the attention of the public, prompting many people to start gulping resveratrol supplements by the fistful, and a major drug company to try developing drugs that mimic the wine ingredient to fight diseases of aging.

Meanwhile, research progressed along two streams. One confirmed the importance of the ingredient and similar compounds in prolonging lifespan or improving health in animals such as worms, fruit flies, and mice. But the other raised major questions about how resveratrol worked -- or if it even did.

The new study, published in the journal Science, details at a precise molecular level how resveratrol and related substances can activate an enzyme called a sirtuin. These enzymes are thought to be involved in DNA repair, inflammation, circadian clocks, and the creation of mitochondria, the power plants of the cell. Increasing the activity of sirtuins has been shown in some animal experiments to lengthen lifespan -- though not in humans.

Sinclair, who is a paid consultant to Sirtris Pharmaceuticals, the Cambridge company he cofounded to hunt for anti-aging drugs, hopes the study will banish the debate about whether the drugs activate sirtuins, allowing the field to move forward. Sinclair also holds patents that are licensed to the company.

“I’ve spent the last 10 years figuring this out,” said Sinclair, who had plaques made for his collaborators as a thank you for their help in untangling the complicated problem. “It almost brings me to tears to think how hard it’s been. There were so many people that didn’t believe in this, that I’m really grateful to the scientists who did stick with us and believe it was right.”

Outside researchers were less enthusiastic. They said the new paper provided a plausible and more nuanced explanation for how resveratrol works, but will do little to clarify the bigger questions in the murky field. The role of a particular sirtuin, called SIRT1, in aging, “is still as clear as mud,” said Brian Kennedy, president of the Buck Institute for Research on Aging, a nonprofit research center in Novato, Calif.

Shortly after the first resveratrol studies were published, outside researchers began to cast doubt on whether the way the researchers had set up the original experiment could have inadvertently influenced their results.

To detect when the SIRT1 enzyme’s activity was kicked into overdrive, Sinclair’s team had attached a fluorescent tag to a molecule that interacted with it. That tag was meant to glow when the enzyme was active -- a signal that could be easily seen by the scientists. But outside researchers later showed that the experiment depended on the presence of the artificial tag, which is not found in the body. Without the fluorescent tag, resveratrol did not increase the enzyme’s activity.

In the new study, a team that included researchers from Sirtris rebuts that critique by describing the specific conditions under which the enzyme can be activated without the fluorescent tags.

Next, the Harvard team randomly mutated the SIRT1 enzyme until finding a version that was resistant to resveratrol’s effect, allowing them to understand better the piece of the enzyme that was essential for their compounds to work. Such evidence, Sinclair said, could help scientists design better versions of drugs.

Matt Kaeberlein of the University of Washington, an author of a 2005 study that pointed out the problem with the fluorescent tag, said the new study clarifies the precise biochemical conditions necessary for resveratrol and similar compounds to activate sirtuins. But he said he still had questions about the details of the enzyme’s activity -- and about the connection to aging.

“I would gauge the current feeling among the broader field as that sirtuins probably impact a subset of age-related diseases, but it’s still unclear how important they are for the aging process in general,” Kaeberlein wrote in an e-mail.

Researchers deeply involved in sirtuin research, however, see the new work as reinforcing the initial and subsequent findings about the molecules. They note that evidence has accumulated that drugs that activate sirtuins can increase endurance of mice and provide major health benefits.

“I feel not only vindicated by this paper, but by a series of studies in the last year and a half that have shown clearly that sirtuins do regulate aging in a wide variety of organisms, including mammals,” said Leonard Guarente, a biology professor at MIT and a consultant to Sirtris. “I think the pendulum swung way too far in terms of skepticism about sirtuins, and I think now we’re starting to come back to reality.”

George Vlasuk, chief executive of Sirtris, which was bought by GlaxoSmithKline for $720 million in 2008, said the results revealed more about how resveratrol-like compounds work, and are guiding research into how to make new drugs.

“It really puts to rest a lot of the controversy that has been surrounding this area for quite some time,” Vlasuk said.

He said Sirtris is preparing reports of how its compounds fared in two clinical trials, of patients with type 2 diabetes and psoriasis.

 

 

Aussie scientist David Sinclair claims anti-ageing superbug breakthrough

An Australian scientist at Harvard claims to have invented a new class of superdrug that could prevent cancer and help people live to be 150. Picture: Supplied

IT sounds too good to be true, but a respected Australian scientist believes he has invented a new class of superdrug that could prevent cancer and Alzheimer's disease.

What's more, Professor David Sinclair says his drugs have the potential to help some people enjoy a healthy life until the age of 150. However, this needs further research.

A paper in the March 8 issue of the journal, Science, explains how the drugs have the ability to switch on the body's defences against ageing.

Three of the drugs are in human trials for the treatment of specific illnesses such as type 2 diabetes and inflammatory bowel disease, says the University of New South Wales geneticist.

Prof Sinclair is most excited about the potential to prevent illness and hopes to prove the drugs will have a dual purpose of treating and preventing disease at the same time.

"My research has been criticised because it sounds too good to be true. This paper shows it is true," he says in a telephone interview from Harvard Medical School, where he is based.

Prof Sinclair's drugs target the enzyme SIRT1, which is switched on naturally by calorie restriction and exercise, but it can also be enhanced through activators such as resveratrol in red wine.

He and his colleagues have developed 4000 synthetic activators. Each one is 100 times more potent than a glass of red wine and the best three are the ones in human trials.

"Our drugs can mimic the benefits of a healthy diet and exercise, but there is no impact on weight," says Prof Sinclair, who suggests the first medicine to be marketed could be for diabetes in about five years.

Once a significant number of people are using the drugs, it will be possible to assess other benefits.

"We can look at 10,000 people and see if they are healthier and living longer than the general population."

In animal tests, overweight mice given synthetic resveratrol were able to run twice as far as slim mice and they lived 15 per cent longer.

"My prediction is that we will delay the onset of diseases and will not have so many people becoming chronically sick in their 50s and 60s," says Prof Sinclair.

The hope is that people will live healthily into their hundreds.

Read more: http://www.news.com.au/world-news/aussie-scientist-david-sinclair-claims-anti-aging-superbug-breakthrough/story-fndir2ev-1226592865613#ixzz2Mta3NsTz