Wennmalm Kristian, Wahlestedt Claes, Larsson Ola
Center for Genomics and Bioinformatics, Karolinska Institutet, Berzelius väg 35, 171 77 Stockholm, Sweden.
Genome Biol. 2005;6(13):R109. doi: 10.1186/gb-2005-6-13-r109. Epub 2005 Dec 16.
The biological mechanisms that underlie aging have not yet been fully identified. Senescence, a phenomenon occurring in vitro, limits the number of cell divisions in mammalian cell cultures and has been suggested to contribute to aging.
We investigated whether the changes in gene expression that occur during mammalian aging and induction of cellular senescence are similar. We compared changes of gene expression in seven microarray datasets from aging human, mouse and rat, as well as four microarray datasets from senescent cells of man and mouse. The datasets were publicly available or obtained from other laboratories. Correlation measures were used to establish similarities of the expression profiles and gene ontology analyses to identify functional groups of genes that are co-regulated. Robust similarities were established between aging in different species and tissues, indicating that there is an aging transcriptome. Although some cross-species comparisons displayed high correlation, intra-species similarities were more reliable. Similarly, a senescence transcriptome was demonstrated that is conserved across cell types. A similarity between the expression signatures of cellular senescence and aging could be established in mouse, but not in human.
Our study is the first to use microarray data from several studies and laboratories for dissection of a complex biological phenotype. We demonstrate the presence of a mammalian aging transcriptome, and discuss why similarity between cellular senescence and aging is apparent in aging mice only.
衰老背后的生物学机制尚未完全明确。细胞衰老,一种在体外发生的现象,限制了哺乳动物细胞培养中的细胞分裂次数,并被认为与衰老有关。
我们研究了哺乳动物衰老过程中发生的基因表达变化与细胞衰老诱导过程中的基因表达变化是否相似。我们比较了来自衰老人类、小鼠和大鼠的七个微阵列数据集以及来自人类和小鼠衰老细胞的四个微阵列数据集的基因表达变化。这些数据集是公开可用的或从其他实验室获得的。使用相关性测量来建立表达谱的相似性,并使用基因本体分析来识别共同调控的基因功能组。在不同物种和组织的衰老之间建立了强大的相似性,表明存在衰老转录组。虽然一些跨物种比较显示出高度相关性,但种内相似性更可靠。同样,证明了一个在不同细胞类型中保守的衰老转录组。在小鼠中可以建立细胞衰老和衰老的表达特征之间的相似性,但在人类中则不能。
我们的研究首次使用来自多个研究和实验室的微阵列数据来剖析复杂的生物学表型。我们证明了哺乳动物衰老转录组的存在,并讨论了为什么细胞衰老和衰老之间的相似性仅在衰老小鼠中明显。