Dietary resveratrol partially mimics caloric restriction

Abstract

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg−1 day−1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.

CR and resveratrol have overlapping effects on alterations in gene expression in multiple tissues

We next examined the transcriptional profiles of CR and resveratrol fed mice for genes that are impacted by the dietary interventions, but are not altered in expression with aging. Such changes in gene expression represent shifts induced by the dietary interventions and can provide clues to mechanisms of action and the degree and nature of CR mimicry by resveratrol. We identified 747 genes that were significantly altered in expression by both CR and resveratrol in the heart (P≤0.01) but were not altered in expression as a result of normal aging. Strikingly, 745 (99.7%) of these gene expression alterations occurred in the same direction for both treatments (Figure 1B). This finding was also observed in muscle (1164/1164 genes, Figure 1B) and brain (1129/1134 genes, Figure 1B). Clearly, resveratrol can mimic a large component of the transcriptional profile of CR in all tissues examined.