Two recent studies have investigated whether resveratrol mimics the effects of calorie-restriction and inhibits various aspects of the ageing process.
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.
A study by Jamie Barger et al. published in the open-access journal Public Library of Science One, adds to a growing body of research linking resveratrol and red wine consumption to a range of beneficial health effects, including brain and mental health, and cardiovascular health.
Previous in vitro and in vivo studies with resveratrol suggest that the compound may help prevent the negative effects of high-calorie diets and has anti-inflammatory and anti-cancer potential, however it has been suggested that in order to gain such benefits from dietary sources, one would have to drink 350 to 1250 litres of red wine. Moreover, resveratrol supplements would not be effective since a daily dose in the region of 2500mg would be required to mimic the effects observed in other studies.
The amount of resveratrol in a bottle of red wine can vary between types of grapes and growing seasons, and can vary between 0.2 and 5.8 milligrams per litre. But nearly all dark red wines - merlot, cabernet, zinfandel, shiraz and pinot noir - contain resveratrol.
The new study suggests that low doses of resveratrol in the diet of middle-aged mice may influence on the genetic levers of aging and may confer special protection on the heart.
“Our findings that a low dose of resveratrol partially mimics calorie restriction at the gene expression level and leads to prevention of some age-related parameters suggests that clinical trials with resveratrol should be conducted to test the relevance of these findings to humans,” wrote lead author Jamie Barger from LifeGen Technologies in Wisconsin.
The researchers fed middle-aged mice (14-months) a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet, and followed the animals until old age (30 months).
The found that animals in the calorie-restriction and low-dose resveratrol groups had altered gene expression profiles in 90 and 92 percent, respectively, in the heart.
The new findings, say the study’s authors, were associated with prevention of the decline in heart function associated with ageing.
In short, a glass of wine or food that contain even small doses of resveratrol are likely to represent “a robust intervention in the retardation of cardiac ageing,” wrote the authors.
Source: Public Library of Science One 3(6): e2264. doi:10.1371/journal.pone.0002264
“A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice” Authors: J.L. Barger et al.
The second study by KJ Pearson et al sought to confirm that resveratrol has anti-ageing properties that protect the heart, bones and eyes from ageing in laboratory mice when given in large enough doses over a long period. The study found resveratrol did not actually extends life, only that it improves the quality of life.
The researchers sought to determine whether the effects of resveratrol in mice were similar to the health benefits shown by dietary restriction. Previous mice studies have 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 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.
The researchers 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. “From a health point of view, the quality of life of these mice at the end of their days is much better. It suggests that resveratrol may extend productive, independent life, rather than just extending life span,” Dr de Cabo said.
The scientists believe resveratrol works by mimicking the effects of a calorie-restricted diet, which is known from animal studies to prolong life and stimulate anti-ageing mechanisms in the body, which help to prevent tissues from being damaged or degraded through wear and tear.
Source: Pearson KJ, Baur JA, Lewis KN, et al. Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. Cell Metab 2008; Jul 4