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After 33 months, grey mouse lemurs who were given a 30%-lower calorie diet experienced an 81% reduction in insulin resistance (inability of cells to utilize insulin) while another group of animals given mega-dose resveratrol (200 milligrams per kilogram of body weight, or 14,000 mg human equivalent dose) experienced a 53% reduction in insulin resistance. Neither calorie restriction nor resveratrol produced any significant beneficial effects at 21 months suggesting beneficial effects for humans may take time to be realized. The study was published in a recent issue of the PLos One journal.

The study is similar to a 12-week controlled trial where calorie restriction was compared to plain resveratrol and a commercially available mixture that included resveratrol (Longevinex®) published in 2008 [Experimental Gerontology] where it was shown that long-term calorie restriction activates 831 genes, short-term calorie restriction 198 genes, short-term resveratrol 225 genes, and short-term Longevinex 1711 genes. If these results are transferable to humans, then most consumers of resveratrol pills will only derive benefits after many months of use whereas a nutriceutical mix of molecules similar to that found in red wine produces a rapid genomic response. – Copyright 2012 Bill Sardi, ResveratrolNews.com

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Abstract

Public Library of Science PLoS ONE March 2012 | Volume 7 | Issue 3 | e34289

Julia Marchal¹, Stéphane Blanc², Jacques Epelbaum³, Fabienne Aujard^1*, Fabien Pifferi¹

1 Mécanismes Adaptatifs et Evolution, UMR 7179 Centre National de la Recherche Scientifique, Muséum National d’Histoire Naturelle, Brunoy, France, 2 Institut Pluridisciplinaire Hubert Curien, Département d’Ecologie, Physiologie, Ethologie UMR 7178 CNRS Université Louis Pasteur, Strasbourg, France, 3 Centre de Psychiatrie et Neuroscience, UMR 894 Inserm, Faculté de Médecine, Université Paris Descartes, Paris, France

Effects of Chronic Calorie Restriction or Dietary Resveratrol Supplementation on Insulin Sensitivity Markers in a Primate, Microcebus murinus

The prevalence of diabetes and hyperinsulinemia increases with age, inducing metabolic failure and limiting lifespan. Calorie restriction (CR) without malnutrition delays the aging process, but its long-term application to humans seems difficult. Resveratrol (RSV), a dietary polyphenol, appears to be a promising CR mimetic that can be easily administered in humans. In this work, we hypothesized that both CR and RSV impact insulin sensitivity in a non-human primate compared to standard-fed control (CTL) animals. Four- to five-year-old male grey mouse lemurs (Microcebus murinus) were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg·day⁻¹·kg⁻¹). Insulin sensitivity and glycemia were assessed using an oral glucose tolerance test (OGTT) and the homeostasis model assessment of insulin resistance (HOMA-IR index) evaluation after 21 or 33 months of chronic treatment. Resting metabolic rate was also measured to assess the potential relationships between this energy expenditure parameter and insulin sensitivity markers. No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals. After 33 months, CR and RSV decreased glycemia after the oral glucose loading without decreasing fasting blood insulin. A general effect of treatment was observed on the HOMA-IR (insulin resistance index), with an 81% reduction in CR animals and 53% in RSV animals after 33 months of treatment compared to control group. Chronic CR and dietary supplementation with RSV affected insulin sensitivity by improving the glucose tolerance of animals without disturbing their baseline insulin secretion. These results suggest that both CR and RSV have beneficial effects on metabolic alterations, although these effects are different in amplitude between the two anti-aging treatments and potentially rely on different metabolic changes.