Revealing System‐level Correlations between Aging and Calorie Restriction using a Mouse Transcriptome

Abstract

The present study aimed to understand the most sensitive biological systems affected during aging and to reveal the systems underlying the crosstalk between aging and the ability of calorie restriction (CR), to effectively slowdown aging. We collected and analyzed 478 aging- and 586 CR-related mouse genes. For the given genes, the biological systems that are significantly related to aging and CR were examined according to three aspects. First, a global characterization by Gene Ontology (GO) was performed, where we found that the transcriptome (a set of genes) for both aging and CR were strongly related in the immune response, lipid metabolism, and cell adhesion functions. Second, the transcriptional modularity found in aging and CR was evaluated by identifying possible functional modules, sets of genes that show consistent expression patterns. Our analyses using the given functional modules, revealed systematic interactions among various biological processes as exemplified by the negative relation shown between lipid metabolism and the immune response at the system level. Third, transcriptional regulatory systems were predicted for both the aging and CR transcriptome. Here, we suggest a systems-biological framework to further understand the most important systems as they age. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (NO. 2007-00376).