Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging.
Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging.
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DOI：
10.1111/acel.12160
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发表时间：
2014-04
期刊：
影响因子：
7.8
通讯作者：
Beekman M
中科院分区：
文献类型：
--
作者：
van den Akker EB;Passtoors WM;Jansen R;van Zwet EW;Goeman JJ;Hulsman M;Emilsson V;Perola M;Willemsen G;Penninx BW;Heijmans BT;Maier AB;Boomsma DI;Kok JN;Slagboom PE;Reinders MJ;Beekman M
随着年龄的增长而出现的身体衰退对未来健康和预期寿命的前景产生了强烈的影响。尽管年龄在疾病病因学中具有深远的作用，但对推动人类衰老过程的分子机制的了解有限。在这里，我们使用了一种基于网络的综合方法，将多个大规模的血液表达研究(2539人)与蛋白质相互作用(PPI)数据相结合，以检测一致共表达的PPI模块，这些模块可能反映了在整个正常衰老过程中发生变化的关键过程。模块检测和对年龄的荟萃分析确定了15个与年龄相关的持续共表达的ppi模块，其中包括一个高度显著的模块(P=3.5x10−38)，它标记了淋巴细胞血细胞计数随年龄的变化(R2=0.603；P=1.9x10−10)。调整纲要中对T细胞激活模块的分析，发现五个持续共表达的PPI模块与年龄密切相关，并包括富含“翻译延长”、“细胞溶解”和“DNA代谢过程”的模块。在一项对3535名个体的独立研究中，五个模块中的四个与按时间顺序排列的年龄一致，这支持了该方法的稳健性。我们发现，根据GenAge数据库的定义，五个模块中有三个模块显著丰富了与衰老相关的基因，并与其中一个模块(包括ASF1A)的高龄预期生存相关。因此，检测到的与年龄相关的和一致共表达的PPI模块可能为未来研究人类衰老的机制提供分子基础。
The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an integrative network-based approach for combining multiple large-scale expression studies in blood (2539 individuals) with protein–protein Interaction (PPI) data for the detection of consistently coexpressed PPI modules that may reflect key processes that change throughout the course of normative aging. Module detection followed by a meta-analysis on chronological age identified fifteen consistently coexpressed PPI modules associated with chronological age, including a highly significant module (P = 3.5 × 10−38) enriched for ‘T-cell activation’ marking age-associated shifts in lymphocyte blood cell counts (R2 = 0.603; P = 1.9 × 10−10). Adjusting the analysis in the compendium for the ‘T-cell activation’ module showed five consistently coexpressed PPI modules that robustly associated with chronological age and included modules enriched for ‘Translational elongation’, ‘Cytolysis’ and ‘DNA metabolic process’. In an independent study of 3535 individuals, four of five modules consistently associated with chronological age, underpinning the robustness of the approach. We found three of five modules to be significantly enriched with aging-related genes, as defined by the GenAge database, and association with prospective survival at high ages for one of the modules including ASF1A. The hereby-detected age-associated and consistently coexpressed PPI modules therefore may provide a molecular basis for future research into mechanisms underlying human aging.
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影响因子：
30.8
作者：
Goering, Harald H. H.;Curran, Joanne E.;Blangero, John
通讯作者：
Blangero, John
影响因子：
4.4
作者：
Derhovanessian, Evelyna;Maier, Andrea B.;Pawelec, Graham
通讯作者：
Pawelec, Graham
DOI：
10.1083/jcb.200507081
发表时间：
2006-02-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Baker DJ;Jeganathan KB;Malureanu L;Perez-Terzic C;Terzic A;van Deursen JM
通讯作者：
van Deursen JM
DOI：
10.1038/nri3198
发表时间：
2012-04-20
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
48
作者：
Marbach, Daniel;Costello, James C.;Kueffner, Robert;Vega, Nicole M.;Prill, Robert J.;Camacho, Diogo M.;Allison, Kyle R.;Kellis, Manolis;Collins, James J.;Stolovitzky, Gustavo
通讯作者：
Stolovitzky, Gustavo