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Metabolic Effects of Resveratrol in Mammals - a Link Between Improved Insulin Action and Aging

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Resveratrol, a polyphenol found in several vegetal sources, has been shown to possess lifespan-promoting properties in yeast and metazoans, including small mammals. While in yeast and low metazoans resveratrol acts mainly by activating the histone deacetylase Sir2, in mammals it appears to target - besides the Sir2 homolog SIRT1 - several crucial pathways for the control of metabolism, including the AMPK and the insulin-IGF1 receptors axis. The action of resveratrol on these pathways has been linked to its capability to i) prolong lifespan following chronic administration to mice and ii) protect from the development of diet-induced obesity and obesity-dependent metabolic disorders. Here we summarise the current understanding on how resveratrol displays its remarkable properties by acting on the control of insulin secretion and by modulation of insulin action in pheripheral insulin-responsive tissues. Since resveratrol has the potential for pharmacological exploitation to prevent the establishment of insulin-resistance and thus postpone - or even prevent - the onset of type 2 diabetes, toxicologic and pharmacodynamics studies in humans have been initiated. These studies show that resveratrol is non-toxic and easily absorbed by humans. As a drawback, its bioavailability is very limited due to the fast metabolic alterations to which it is subjected in the plasma. Therefore, we also review here the efforts that have been made - in the drug discovery field - to identify new molecules endowed with resveratrol-like pharmacological properties but with better bioavailability, which could prove to possess therapeutic potential.





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Keywords: AMPK; PI 3-kinase; Resveratrol; insulin sensitivity; lifespan; sirtuins

Document Type: Research Article

Publication date: 01 December 2008

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  • Current Aging Science publishes frontier review and experimental articles in all areas of aging and age-related research that may influence longevity. This multidisciplinary journal will help in understanding the biology and mechanism of aging, genetics, pathogenesis, intervention of normal aging process and preventive strategies of age-related disorders. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, clinical, molecular, and animal models, including lower organism models (e.g., yeast, Caenorhabditis elegans and Drosophila). In addition to the affect of aging on integrated systems, the journal also covers original articles on recent research in fast emerging areas of adults stem cells, brain imaging, calorie restriction, immunosenescence, molecular diagnostics, pharmacology and clinical aspects of aging. Manuscripts are encouraged that relate to developmental programming of aging and the synergistic mechanism of aging with cardiovascular diseases, obesity and neurodegenerative disorders.

    Book reviews, meeting reports and letters-to-the-editor and drug clinical trial studies are also published. The journal is essential reading for researchers, educators and physicians with interest in aging, age-related dementia and Alzheimer's disease and longevity. Current Aging Science provides a comprehensive coverage of the current state of aging research for gerontologists, neuroscientists, clinicians, health science planners, granting agencies and pharmaceutical scientists.

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