Department of Neuroscience, Evelyn F and William L. McKnight Brain Institute, University of Florida Gainesville, FL, USA.
Front Aging Neurosci. 2010 May 19;2. doi: 10.3389/neuro.24.006.2010. eCollection 2010.
Aplysia californica is a powerful experimental system to study the entire scope of genomic and epigenomic regulation at the resolution of single functionally characterized neurons and is an emerging model in the neurobiology of aging. First, we have identified and cloned a number of evolutionarily conserved genes that are age-related, including components of apoptosis and chromatin remodeling. Second, we performed gene expression profiling of different identified cholinergic neurons between young and aged animals. Our initial analysis indicates that two cholinergic neurons (R2 and LPl1) revealed highly differential genome-wide changes following aging suggesting that on the molecular scale different neurons indeed age differently. Each of the neurons tested has a unique subset of genes differentially expressed in older animals, and the majority of differently expressed genes (including those related to apoptosis and Alzheimer's disease) are found in aging neurons of one but not another type. The performed analysis allows us to implicate (i) cell specific changes in histones, (ii) DNA methylation and (iii) regional relocation of RNAs as key processes underlying age-related changes in neuronal functions and synaptic plasticity. These mechanisms can fine-tune the dynamics of long-term chromatin remodeling, or control weakening and the loss of synaptic connections in aging. At the same time our genomic tests revealed evolutionarily conserved gene clusters associated with aging (e.g., apoptosis-, telomere- and redox-dependent processes, insulin and estrogen signaling and water channels).
太平洋扇贝多肽是一个强大的实验系统，可在单个功能表征神经元的分辨率下研究基因组和表观基因组调控的全部范围，并且是衰老神经生物学中的新兴模型。首先，我们已经鉴定和克隆了一些与年龄相关的进化上保守的基因，包括凋亡和染色质重塑的组成部分。其次，我们对年轻和年老动物之间的不同鉴定胆碱能神经元进行了基因表达谱分析。我们的初步分析表明，两种胆碱能神经元（R2 和 LPl1）在衰老后显示出高度差异的全基因组变化，这表明在分子水平上，不同的神经元确实以不同的方式衰老。在老年动物中，每种测试的神经元都有一组独特的差异表达基因，大多数差异表达的基因（包括与凋亡和阿尔茨海默病相关的基因）存在于一种但不是另一种类型的衰老神经元中。所进行的分析使我们能够暗示（i）组蛋白、（ii）DNA 甲基化和（iii）RNA 的区域重定位作为神经元功能和突触可塑性与年龄相关变化的关键过程。这些机制可以微调长期染色质重塑的动态，或者控制衰老过程中突触连接的减弱和丧失。同时，我们的基因组测试揭示了与衰老相关的进化上保守的基因簇（例如凋亡、端粒和氧化还原依赖过程、胰岛素和雌激素信号以及水通道）。
