“Red wine drug could make elderly more vigorous but not live longer,” is the headline in The Daily Telegraph . A research study has found that an extract of red wine did not appear to extend the lifespan of mature mice. The extract resveratrol, a chemical component of red wine, is also found in pomegranates and nuts. It is thought to have a “widespread influence on ageing”, the newspaper reports, and hopes were that it would extend lifespan too.
This comprehensive research found that resveratrol had a range of beneficial effects, including decreasing the markers of inflammation, reducing cataracts and preserving bone density in the mice. However, there was no effect on mouse survival. Red wine drinkers will need to wait for the results of the currently registered clinical trials in humans to see whether there is any benefit for them.
Where did the story come from?
Dr Kevin J Pearson from the laboratory of experimental gerontology at the National Institutes of Health in Baltimore and 26 colleagues, mainly from the US, but also from Australia and Spain, carried out this research. This work was supported by multiple grants from the American Heart Association, the National Institutes of Health, a Spanish organisation, the Paul F Glenn Laboratories for the Biological Mechanisms of Aging and personal contributions. Two authors acknowledge links with Sirtris, the GlaxoSmithKline company that holds the patent on SRT501, a proprietary formulation of resveratrol. The study was published in the peer-reviewed medical journal: Cell Metabolism .
What kind of scientific study was this?
This was an experimental animal study in which the researchers sought to determine whether the effects of resveratrol in mice were similar to the health benefits shown by dietary restriction. It is already known that keeping mice on a calorie-restricted diet of 30%–50% below normal, or restricting them to feeding every other day, can show a delay in the onset of age-related diseases, improved stress resistance and slower decline in function. Such a restrictive diet is unlikely to be acceptable or safe in humans and so research has focused on finding chemical compounds that can produce similar physiological and genetic changes as dietary restriction.
Some studies have already shown that resveratrol, chemically a small polyphenol, can extend the life of some yeasts, roundworms and fruit flies, and is being tested in invertebrate fish. Mice studies have also shown that resveratrol improves the health and survival of obese mice fed a high-calorie diet. So, in this study, the researchers set about seeing if resveratrol could improve the health of non-obese mice, and if so, if this was due to the ability of the chemical to mimic the effects of dietary restriction.
The researchers took one-year-old mice and fed some of them a standard control diet., Others had a restricted diet and were fed every other day, while another group,was fed freely from a high-calorie diet. Three doses of resveratol were added to the feeds, and all the groups of mice were compared with a control group, which was not given resveratrol. The doses of resveratrol were either 100mg, 400mg or 2,400mg per kg of food.
What were the results of the study?
The researchers report five main results of their study:
- Genetically, resveratrol mimics the “transcriptional effects” of dietary restriction. For this part of the study, the researchers performed genetic tests on the nucleic acid and genes extracted from liver, muscle and fat of the mice.
- Resveratrol delays functional decline. The researchers performed eleven tests on both the live mice and some after natural death. These ranged from tests of co-ordination to bone strength and volume, bone density (tested by CT scan) and looking for any cataracts. In most cases, the treated mice on a standard diet were healthier than the non-treated mice.
- Resveratrol improved vascular function. This was tested by looking at cholesterol levels, blood vessel hardening, and by measuring oxidative stress in the dissected blood vessels.
- Resveratrol did not increase overall survival or maximum lifespan in the mice on a standard diet. In the mice fed a high-calorie diet, resveratrol increased remaining life span of one-year-old mice by an average of 26% for the group given low-dose resveratrol compared with the control group. Those given a high-dose of reservatrol increased their life span by an average of 25%. This survival gain was not significantly different from that of non-obese standard diet control mice.
- Resveratrol had no effect on histopathological changes (those seen under the microscope), in the heart, kidneys, liver, spleen, lungs and pancreas.
What interpretations did the researchers draw from these results?
The researchers summarise their results in mice by saying that resveratrol “induces gene expression patterns in multiple tissues that parallel those induced by dietary restriction and every-other-day feeding. The resveratrol-fed elderly mice show a marked reduction in signs of ageing, but mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age”.
They conclude that their findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the lifespan of freely feeding animals when started midlife.
What does the NHS Knowledge Service make of this study?
This is an extensive and comprehensive study into the effects of resveratrol on a range of biological and genetic markers of ageing. Published as a short article with supplementary material, it has been a major undertaking by a network of scientists. The validity and reliability of the results will need careful assessment by other researchers knowledgeable in the field of ageing as each of the wide range of advantages reported will themselves need testing in humans.
The benefits listed in this research for mice included:
- Reduced protein excretion from the kidneys.
- Decreased inflammation.
- Decreased cell death in the lining of blood vessels.
- Increased elasticity in the aorta, the main blood vessel from the heart.
- Improved motor coordination.
- Reduced cataract formation.
- Preserved bone mineral density.
These outcomes will be of interest to humans too, and the ongoing studies of the chemical in the currently registered clinical trials will be awaited with interest.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Independent, 4 July 2008
The Daily Telegraph, 4 July 2008
Links to the science
Cell Metab 2008; Jul 4 [Epub ahead of print]