A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice

TLDR

High‑dose resveratrol has been shown to extend lifespan in invertebrates and reduce early mortality in high‑fat‑diet mice. Mice aged 14 to 30 months were fed either a control diet, a low‑dose resveratrol (4.9 mg kg⁻¹ day⁻¹), or a calorie‑restricted diet, and genome‑wide transcriptional profiles were examined. Low‑dose resveratrol produced a transcriptional profile overlapping that of calorie restriction in heart, skeletal muscle, and brain, inhibiting aging‑associated gene expression, preserving cardiac function, enhancing insulin‑mediated glucose uptake, and suggesting chromatin‑mediated retardation of aging, thereby mimicking key aspects of calorie restriction at human‑achievable doses.

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.