Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules

Abstract

In this work we present a method for the differential analysis of gene co-expression networks and apply this method to look for large-scale transcriptional changes in aging. We derived synonymous gene co-expression networks from AGEMAP expression data for 16-month-old and 24-month-old mice. We identified a number of functional gene groups that change co-expression with age. Among these changing groups we found a trend towards declining correlation with age. In particular, we identified a modular (as opposed to uniform) decline in general correlation with age. We identified potential transcriptional mechanisms that may aid in modular correlation decline. We found that computationally identified targets of the NF-ΚB transcription factor decrease expression correlation with age. Finally, we found that genes that are prone to declining co-expression tend to be co-located on the chromosome. Our results conclude that there is a modular decline in co-expression with age in mice. They also indicate that factors relating to both chromosome domains and specific transcription factors may contribute to the decline.

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

“…Alternatively, age‐related gene expression changes might also be too subtle to achieve statistical significance in classical differential expression analyses. The analysis of gene co‐expression networks provides an opportunity to analyze transcriptional deregulation at a higher level of complexity (Southworth et al ., 2009), and our findings demonstrate a reduced connectivity of gene expression in old samples. These results are in agreement with earlier findings in aging mice (Southworth et al ., 2009) and suggest that the age‐related erosion of methylation patterns is accompanied by a reduced fine‐tuning in the transcriptional circuitry, possibly through methylation‐dependent changes in transcription factor binding (Yuan et al ., 2015).…”

“…However, it has been described that aging mouse tissues have a decreased correlation of gene expression (Southworth et al ., 2009). We therefore computed pairwise Pearson correlation coefficients between the 30% most variable genes in the young and old sample groups (see Experimental procedures for details).…”

Biochemical integration of blood redox state in captive zebra finches (Taeniopygia guttata)

“…First, our investigation was restricted to subadult animals (around 45days old), fully independent but not yet fully sexually mature. Studies on gene and metabolic networks suggest that these systems can become less integrated as the individual ages, so becoming noisier and less stable because of a decrease in the effectiveness of communication among functional units (Csermely and Soti, 2006;Xue et al, 2007;Southworth et al, 2009;Soltow et al, 2010). So, in future studies it will be important to evaluate network robustness in older individuals to see whether any changes in the degree of integration of the network mirror a signal of senescence.…”

Loss of integration is associated with reduced resistance to oxidative stress

“…Giuliani et al, 2004;Csermely and Sőti, 2006;Tun et al, 2006;Parter et al, 2007;Southworth et al, 2009). The extent to which exposure to stressors is detrimental for the organism depends on the nature and strength of the stressor.…”