Ageing transcriptome meta-analysis reveals similarities and differences between key mammalian tissues

Abstract

By combining transcriptomic data with other data sources, inferences can be made about functional changes during ageing. Thus, we conducted a meta-analysis on 127 publicly available microarray and RNA-Seq datasets from mice, rats and humans, identifying a transcriptomic signature of ageing across species and tissues. Analyses on subsets of these datasets produced transcriptomic signatures of ageing for brain, heart and muscle. We then applied enrichment analysis and machine learning to functionally describe these signatures, revealing overexpression of immune and stress response genes and underexpression of metabolic and developmental genes. Further analyses revealed little overlap between genes differentially expressed with age in different tissues, despite ageing differentially expressed genes typically being widely expressed across tissues. Additionally we show that the ageing gene expression signatures (particularly the overexpressed signatures) of the whole meta-analysis, brain and muscle tend to include genes that are central in protein-protein interaction networks. We also show that genes underexpressed with age in the brain are highly central in a co-expression network, suggesting that underexpression of these genes may have broad phenotypic consequences. In sum, we show numerous functional similarities between the ageing transcriptomes of these important tissues, along with unique network properties of genes differentially expressed with age in both a protein-protein interaction and co-expression networks.

Keywords: Artificial Intelligence; functional genomics; machine learning; microarray; mitochondria.

Figure 1

Overlap of this current work’s meta-analysis (Palmer et al.) with the microarray signature of mammalian ageing currently hosted on GenAge (de Magalhães, et al.) [4]). (A) Gives the overlap for genes overexpressed with age, while (B) gives the overlap for genes underexpressed with age. The p-values given are the result of a hypergeometric test, testing the significance of the given overlap using all other protein-coding genes as a background (i.e. all genes not differentially expressed in the direction of the given analysis).

Figure 2

Overlap of the global and tissue-specific results of this meta-analysis. (A) Gives the overlap for genes overexpressed with age while (B) gives the overlap for genes underexpressed with age.