Aging mice show a decreasing correlation of gene expression within genetic modules.
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-KappaB 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.
Southworth
Lucinda K
LK
Biomedical Informatics, Stanford University, Stanford, California, United States of America.
Owen
Art B
AB
Kim
Stuart K
SK
D000375:Aging / Q000235:genetics*; D000818:Animals; D002875:Chromosomes; D015870:Gene Expression; D053263:Gene Regulatory Networks; D008722:Methods; D051379:Mice; D016328:NF-kappa B; D014157:Transcription Factors; D014158:Transcription, Genetic
D016328:NF-kappa B; D014157:Transcription Factors