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Mice on normal diets were fed a daily, relatively low dose of resveratrol obtained from either a synthetic source or from a whole-grape extract enriched with resveratrol. A control group of mice fed a normal diet without resveratrol supplementation and a calorie-restricted group were also evaluated. Total calorie intake was identical in the resveratrol, grape extract, and control groups, and 40% less in the calorie-restricted group.
At the end of an eight-week feeding schedule, the animals’ livers were harvested in order to prepare RNA (the biochemical cousin of DNA) for gene-expression profiling. The samples were specially prepared for analysis with DNA microarrays, or “gene chips,” containing a full set of characterized mouse genes (the Affymetrix GeneChip® contains a total of over 45,000 probe sets, representing a complete set of over 34,000 genes of the mouse genome). Gene-expression levels were determined using statistical methods that ensure a high degree of confidence in the data.*
Both mouse groups that received resveratrol showed significant changes in the expression of key genes, confirming that even at the relatively low doses used in this study, there was a notable biological effect. The differentially expressed genes control over 100 different molecular pathways, including those related to metabolism (primarily metabolism of carbohydrates and lipids), DNA repair, and the regulation of cell death. Since the genes involved are in key biological pathways, they are likely to be responsible for at least some of resveratrol’s biological effects. Furthermore, significant results were achieved using a dose of synthetic resveratrol that was more than 10-fold lower than that used in the Harvard study.
Animals fed grape extract received resveratrol and other components of whole-grape extract.** Their gene-expression response would therefore be expected to reflect effects of both resveratrol and other grape components. Genes that significantly changed in expression in the grape extract group are found in molecular pathways involved in carbohydrate metabolism and biosynthesis (such as the creation of blood sugars), and lipid metabolism and biosynthesis (such as the creation or reduction of cholesterol and fatty acids).
Interestingly, scientists noted a significant overlap—about 65%—when they compared the gene-expression patterns of the resveratrol and grape extract groups. While expected, these results confirm the similar effects of pure synthetic resveratrol and grape extract-derived resveratrol on gene expression in animals. The gene-expression effects of “low-dose” resveratrol were similar to those seen in calorie-restricted mice: about 55% similarity between the calorie-restricted and resveratrol groups, and 52% similarity between the calorie-restricted and grape extract-supplemented groups.
A method known as molecular pathway analysis can be applied to the gene-expression profiling results in order to identify the key regulatory pathways affected by the various treatments of resveratrol, grape extract, and caloric restriction. Displayed in Figures 1 and 2, these data show which pathways are specific to the different treatments, as well as pathways that are shared between or among the treatments.
Figure 1 shows the results for genes in pathways that are related to biological processes involving DNA; as shown by the overlap, 20 differentially expressed genes involved in DNA-related processes are regulated in the same fashion in animals receiving synthetic resveratrol, grape extract, or caloric restriction. These data suggest that the three treatments share some common features with respect to how genes involved in DNA processing are controlled through gene expression.
A similar approach was used to analyze genes involved in lipid metabolism. As shown in Figure 2, 10 genes involved in pathways related to lipid metabolism are commonly regulated by resveratrol, grape extract, and caloric restriction. These data are just a subset of the entire analysis. In total, 159 different molecular pathways were found to be commonly regulated by these three different treatments.
Resveratrol and grape extract produce strongly similar effects, based on the gene-expression responses demonstrated in mice fed a relatively low dose of these compounds. Comparison of these groups with calorie-restricted mice shows a significant overlap in the three treatments’ regulation of similar biological pathways. These data add to the accumulating evidence that resveratrol triggers a biological response in mammals that is similar to that observed with caloric restriction, an intervention that is known to extend life span and protect against age-related diseases.2-5 These effects are observed even at a relatively low dose of resveratrol, indicating that a human-equivalent dose can be obtained through dietary supplementation with high-quality resveratrol products.
Article Produced By
Life Extension
https://www.lifeextension.com/magazine/2007/3/report_resveratrol/Page-04
(All these Articles can be read from this URL:
https://markethive.com/group/ama/blog/the-role-of-resveratrol-in-achieving-optimal-health-p5
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