Transcription profiling of mouse heart, brain, and skeletal muscle to determine the effect of age, calorie restriction and resveratrol on gene expression

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. 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. Experiment Overall Design: Heart, neocortex tissue, and gastrocnemius muscle was collected from young and old mice at 5 and 30 months of age, respectively; mice were subjected to either a calorie restricted diet or a control diet supplemented with resveratrol高剂量白藜芦醇在多项无脊椎动物研究中被证实可延长其寿命，并可预防高脂饮食小鼠的早期死亡。我们对从中年（14月龄）至老年（30月龄）的小鼠分别饲喂对照饮食、低剂量白藜芦醇（4.9 mg·kg⁻¹·d⁻¹）或限食（calorie restricted, CR）饮食，并对其开展全基因组转录谱（genome-wide transcriptional profiles）分析。我们发现，限食与白藜芦醇在心脏、骨骼肌与大脑中存在显著的转录组重叠现象。两种膳食干预手段均能抑制与心脏及骨骼肌衰老相关的基因表达特征。基因表达谱分析结果显示，限食与白藜芦醇或可通过改变染色质结构与转录过程，延缓衰老的若干进程。在人体可轻易达到的剂量范围内，白藜芦醇符合模拟限食部分效应的膳食化合物的定义。实验整体设计：分别采集5月龄年轻小鼠与30月龄老年小鼠的心脏、新皮层组织及腓肠肌；小鼠被分配接受限食饮食，或饲喂添加白藜芦醇的对照饮食。