Are the 50's, the transition decade, in choroid plexus aging?

Abstract

The choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain, and from the circulatory system, shaping brain function in health and in pathology. Previous studies in rodents have revealed altered transcriptome both during aging and in various diseases of the central nervous system, including Alzheimer's disease. In the present study, a high-throughput sequencing of the CP transcriptome was performed in postmortem samples of clinically healthy individuals aged 50's through 80's. The data shows an age-related profile, with the main changes occurring in the transition from the 50's to the 60's, stabilizing thereafter. Specifically, neuronal and membrane functions distinguish the transcriptome between the 50's and the 60's, while neuronal and axon development and extracellular structure organization differentiate the 50's from the 70's. These findings suggest that changes in the CP transcriptome occur early in the aging process. Future studies will unravel whether these relate with processes occurring in late- onset brain diseases.

Keywords: Aging; Choroid plexus; High-throughput sequencing; Human.

Fig. 1

The Venn diagram of differentially expressed genes (DEGs) in each group comparison (a). Heatmap of 311 DEGs presented in at least two comparisons, rows represent genes and columns each sample. Bars are colored according to each group G50 (gold), G60 (light gray), and G70 (dark gray). Gene expressions are scaled by blue colors, and light blue indicates lower expression and dark blue higher expression (b). Plot of log2 (ratio expression) of overlapping gene between the comparison analysis (c)

Fig. 2

k-means clustering of genes differentially expressed in at least one comparison (n = 311 genes). The x-axis shows the sample ages, and y-axis represents the normalized expression counts value after z-score normalization. Cluster 1 (n = 60 genes), Cluster 2 (n = 134 genes), and Cluster 3 (n= 117 genes)

Fig. 3

Enrichment analysis of GOs of differentially expressed genes (DEGs). a Venn diagram of GOs overrepresented in each analysis. b Heatmap of overlapping GOs in the analysis, rows represent GOs and columns represent specific analysis. Yellow color indicates that the GO is present in the specific analysis and black indicates the absence. c Similarity GO analysis. Each node or diamond represents a GO in Cluster 2 or 3, respectively. Sizes correspond to the number of genes observed in the category and FDR is scaled by color yellow to red according to the range of 0.05 to 10⁻⁴. Edges represent the similarity between the GOs