Abstract

Effects of an 18-month treatment with a moderate, chronic caloric restriction (CR) or an oral supplementation with resveratrol (RSV), a potential CR mimetic, on cognitive and motor performances were studied in non-human primates, grey mouse lemurs (Microcebus murinus).Thirty-three adult male mouse lemurs were assigned to three different groups: a control (CTL) group fed ad libitum, a CR group fed 70% of the CTL caloric intake, and an RSV group (RSV supplementation of 200 mg.kg−1.day−1) fed ad libitum. Three different cognitive tests, two motor tests, one emotional test and an analysis of cortisol level were performed in each group.Compared to CTL animals, CR or RSV animals did not show any change in motor performances evaluated by rotarod and jump tests, but an increase in spontaneous locomotor activity was observed in both groups. Working memory was improved by both treatments in the spontaneous alternation task. Despite a trend for CR group, only RSV supplementation increased spatial memory performances in the circular platform task. Finally, none of these treatments induced additional stress to the animals as reflected by similar results in the open field test and cortisol analyses compared to CTL animals.The present data provided the earliest evidence for a beneficial effect of CR or RSV supplementation on specific cognitive functions in a primate. Taken together, these results suggest that RSV could be a good candidate to mimic long-term CR effects and support the growing evidences that nutritional interventions can have beneficial effects on brain functions even in adults.

Highlights

  • With the increase of human longevity have appeared a significant number of age-related diseases and more age-related brain dysfunctions

  • A cohort of adult grey mouse lemurs was followed in order to evaluate their cognitive and motor performances as well as their emotionality after 18 months of chronic moderate Caloric restriction (CR) or RSV supplementation

  • In humans a 3-month 30% caloric restriction led to a significant increase in verbal memory scores and was correlated with decreased fasting plasma levels of insulin and high sensitive C-reactive protein [2]

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Summary

Introduction

With the increase of human longevity have appeared a significant number of age-related diseases and more age-related brain dysfunctions. A growing interest for non-genetic anti-aging strategies development as food protocols is revealed. Caloric restriction (CR) is the only non-genetic manipulation known to increase longevity and delay age-related diseases in various species, including mammals (see [1] for review). Given that CR is difficult to implement in humans due to social and practical constraints, development of CR mimetic compounds might be a suitable alternative. Resveratrol (RSV), a natural polyphenolic compound that activates proteins implicated in energy metabolism homeostasis, seems to be a promising anti-aging molecule [7,8,9,10,11] which could slow brain functions decline with age

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