Department of Neuroscience, McKnight Brain Institute, University of Florida, P.O. Box 100244, Gainesville, FL 32610-0244, USA.
Mech Ageing Dev. 2011 Jan-Feb;132(1-2):8-19. doi: 10.1016/j.mad.2010.10.006. Epub 2010 Nov 3.
We measured changes in gene expression, induced by aging and caloric restriction (CR), in three hippocampal subregions. When analysis included all regions, aging was associated with expression of genes linked to mitochondrial dysfunction, inflammation, and stress responses, and in some cases, expression was reversed by CR. An age-related increase in ubiquintination was observed, including increased expression of ubiquitin conjugating enzyme genes and cytosolic ubiquitin immunoreactivity. CR decreased cytosolic ubiquitin and upregulated deubiquitinating genes. Region specific analyses indicated that CA1 was more susceptible to aging stress, exhibiting a greater number of altered genes relative to CA3 and the dentate gyrus (DG), and an enrichment of genes related to the immune response and apoptosis. CA3 and the DG were more responsive to CR, exhibiting marked changes in the total number of genes across diet conditions, reversal of age-related changes in p53 signaling, glucocorticoid receptor signaling, and enrichment of genes related to cell survival and neurotrophic signaling. Finally, CR differentially influenced genes for synaptic plasticity in CA1 and CA3. It is concluded that regional disparity in response to aging and CR relates to differences in vulnerability to stressors, the availability of neurotrophic, and cell survival mechanisms, and differences in cell function.
我们测量了衰老和热量限制（CR）诱导的三个海马亚区基因表达的变化。当分析包括所有区域时，衰老与与线粒体功能障碍、炎症和应激反应相关的基因表达有关，在某些情况下，CR 可逆转这种表达。观察到泛素化的年龄相关性增加，包括泛素连接酶基因和胞质泛素免疫反应性的表达增加。CR 降低了胞质泛素并上调了去泛素化基因。区域特异性分析表明，CA1 对衰老应激更敏感，与 CA3 和齿状回（DG）相比，改变的基因数量更多，并且与免疫反应和细胞凋亡相关的基因富集。CA3 和 DG 对 CR 的反应更为明显，在不同饮食条件下总基因数发生明显变化，逆转了与 p53 信号、糖皮质激素受体信号相关的年龄相关变化，以及与细胞存活和神经营养信号相关的基因富集。最后，CR 对 CA1 和 CA3 中的突触可塑性相关基因产生了不同的影响。结论是，对衰老和 CR 的反应的区域差异与对应激源的脆弱性、神经营养和细胞存活机制的可用性以及细胞功能的差异有关。
