Huang Jian-Hua, Shen Zi-Yin, Wu Bin
Institute of Integrative Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2008 Jan;28(1):47-50.
To investigate the effect and its mechanism of Epimedium flavanoids (EF) in retarding aging with different systematic viewpoints.
Hypothalamus, pituitary, adrenal and lymphocytes taken from 4-, 10-, 18-, 24-month old rats and from EF treated 24-month old rats were used to measure whole genome mRNA expression by gene array. Serum samples were used for metabonomic assay with high performance liquid chromatography. Using specific gene chip for NF-kappaB signaling pathway to detect the gene expression of the molecule related to that pathway in lymphocytes. Then, a neural network (NN) model was established upon the data obtained to quantitatively evaluate the degree of aging and the efficacy of drug intervention.
Gene expression of 199 genes showedan age-dependent pattern, most of which were reversed by EF, and the output of NN model showed that EF made the transcriptomics of 24-month old rats to 8-13 months. Seventeen metabolites among the 1,885 peaks detected were identified to have significant age-depending changes, and EF intervention reset the level of metabolites to a younger (18-month) level. The integral level of gene expression for NF-kappaB signaling pathway decreased significantly along with the increasing of age, and was significantly elevated by EF, NN model showed it approached to 10.5-month old.
Phenotype of aging at different levels demonstrates a common age-dependent trend; EF can reverse this age-dependent change at different levels in a synchronous manner.
从不同系统观点探讨淫羊藿黄酮(EF)延缓衰老的作用及其机制。
取4、10、18、24月龄大鼠及EF处理的24月龄大鼠的下丘脑、垂体、肾上腺和淋巴细胞,采用基因芯片检测全基因组mRNA表达。血清样本用于高效液相色谱代谢组学分析。使用NF-κB信号通路特异性基因芯片检测淋巴细胞中与该通路相关分子的基因表达。然后,根据获得的数据建立神经网络(NN)模型,定量评估衰老程度和药物干预效果。
199个基因的表达呈现年龄依赖性模式,其中大部分被EF逆转,NN模型输出显示EF使24月龄大鼠的转录组学状态恢复到8-13月龄。在检测到的1885个峰中,有17种代谢物被鉴定出具有显著的年龄依赖性变化,EF干预使代谢物水平恢复到较年轻(18月龄)的水平。NF-κB信号通路的基因表达整体水平随年龄增长显著下降,EF使其显著升高,NN模型显示其接近10.5月龄大鼠的水平。
不同水平的衰老表型呈现共同的年龄依赖性趋势;EF可同步逆转不同水平的这种年龄依赖性变化。