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Meta-analysis of age-related gene expression profiles identifies common signatures of aging

机译:年龄相关基因表达谱的荟萃分析确定了衰老的常见特征

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摘要

>Motivation: Numerous microarray studies of aging have been conducted, yet given the noisy nature of gene expression changes with age, elucidating the transcriptional features of aging and how these relate to physiological, biochemical and pathological changes remains a critical problem.>Results: We performed a meta-analysis of age-related gene expression profiles using 27 datasets from mice, rats and humans. Our results reveal several common signatures of aging, including 56 genes consistently overexpressed with age, the most significant of which was APOD, and 17 genes underexpressed with age. We characterized the biological processes associated with these signatures and found that age-related gene expression changes most notably involve an overexpression of inflammation and immune response genes and of genes associated with the lysosome. An underexpression of collagen genes and of genes associated with energy metabolism, particularly mitochondrial genes, as well as alterations in the expression of genes related to apoptosis, cell cycle and cellular senescence biomarkers, were also observed. By employing a new method that emphasizes sensitivity, our work further reveals previously unknown transcriptional changes with age in many genes, processes and functions. We suggest these molecular signatures reflect a combination of degenerative processes but also transcriptional responses to the process of aging. Overall, our results help to understand how transcriptional changes relate to the process of aging and could serve as targets for future studies.>Availability:>Contact: >Supplementary information: are available at Bioinformatics online.
机译:>动机:已经进行了许多衰老的微阵列研究,但是鉴于基因表达随年龄的变化具有嘈杂的性质,阐明衰老的转录特征以及这些转录特征与生理,生化和病理变化之间的关系仍然至关重要问题。>结果:我们使用来自小鼠,大鼠和人类的27个数据集进行了与年龄相关的基因表达谱的荟萃分析。我们的研究结果揭示了衰老的几种常见特征,包括56个随年龄持续过度表达的基因,其中最重要的是APOD,以及17个随年龄过度表达的基因。我们表征了与这些特征相关的生物学过程,发现与年龄相关的基因表达变化最明显地涉及炎症和免疫反应基因以及与溶酶体相关的基因的过表达。还观察到胶原蛋白基因和与能量代谢有关的基因,特别是线粒体基因的低表达,以及与细胞凋亡,细胞周期和细胞衰老生物标志物有关的基因表达的改变。通过采用强调敏感性的新方法,我们的工作进一步揭示了许多基因,过程和功能中随着年龄增长而产生的未知转录变化。我们建议这些分子签名反映了退化过程的组合,但也反映了衰老过程的转录反应。总体而言,我们的结果有助于理解转录变化与衰老过程的关系,并可以作为将来研究的目标。>可用性: >联系方式: >补充信息:< / strong>,可在线访问生物信息学。

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