Molecular Developmental Biology, Institute of Molecular Biosciences, Faculty for Biosciences & Cluster of Excellence 'Macromolecular Complexes', Johann Wolfgang Goethe University, Frankfurt am Main, Germany ; Molecular Bioinformatics, Institute of Computer Science, Faculty of Computer Science and Mathematics & Cluster of Excellence 'Macromolecular Complexes', Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Molecular Developmental Biology, Institute of Molecular Biosciences, Faculty for Biosciences & Cluster of Excellence 'Macromolecular Complexes', Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
PLoS One. 2013 Dec 20;8(12):e83109. doi: 10.1371/journal.pone.0083109. eCollection 2013.
Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.
生物系统的衰老受多种过程控制，这些过程对基因表达有潜在影响。在这里，我们报告了真菌衰老模型 Podospora anserina 的全基因组转录组分析。从三个特定年龄的个体中汇集总 RNA，并通过 SuperSAGE（基因表达的序列分析）进行分析。生物信息学分析确定了在衰老过程中受影响的不同分子途径。虽然与核糖体和蛋白酶体质量控制系统相关的转录物的丰度被发现随着衰老而降低，与自噬相关的转录物增加，表明自噬可能作为一种补偿性的质量控制途径。与能量代谢相关的转录本谱，包括线粒体功能，在衰老过程中被鉴定为波动。将野生型转录本（在衰老过程中持续下调）与长寿的铜摄取突变体 grisea 中的下调转录本进行比较，验证了细胞铜代谢在衰老过程中变化的相关性。总的来说，我们 (i) 提出了一个独特的与实验性衰老模型 P. anserina 的纵向研究相关的年龄相关数据集，这代表了未来在各种生物体中进行研究的参考资源，(ii) 表明自噬是一种关键的质量控制途径，一旦其他途径失效，它就会变得活跃，(iii) 为随后的实验研究提出了可测试的预测。
