MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain

Abstract

Changes in gene expression levels determine differentiation of tissues involved in development and are associated with functional decline in aging. Although development is tightly regulated, the transition between development and aging, as well as regulation of post-developmental changes, are not well understood. Here, we measured messenger RNA (mRNA), microRNA (miRNA), and protein expression in the prefrontal cortex of humans and rhesus macaques over the species' life spans. We find that few gene expression changes are unique to aging. Instead, the vast majority of miRNA and gene expression changes that occur in aging represent reversals or extensions of developmental patterns. Surprisingly, many gene expression changes previously attributed to aging, such as down-regulation of neural genes, initiate in early childhood. Our results indicate that miRNA and transcription factors regulate not only developmental but also post-developmental expression changes, with a number of regulatory processes continuing throughout the entire life span. Differential evolutionary conservation of the corresponding genomic regions implies that these regulatory processes, although beneficial in development, might be detrimental in aging. These results suggest a direct link between developmental regulation and expression changes taking place in aging.

Gene expression‐based drug repurposing to target aging

“…We analysed data from seven, published, microarray‐based studies of age‐related changes in RNA expression (Barnes et al, 2011; Berchtold et al, 2008; Colantuoni et al, 2011; Kang et al, 2011; Lu et al, 2004; Maycox et al, 2009; Somel et al, 2010, 2011 ). The data came from 22 different brain regions, and the ages of the donors ranged from 20 to 106 years (Figure 1a and Supporting Information Figure S1a).…”

Upregulation of a small vault RNA (svtRNA2-1a) is an early event in Parkinson disease and induces neuronal dysfunction

“…In the human superior frontal gyrus, 30 the highest levels of svtRNA2-1a were detected at early postnatal developmental stages. After the first year, the amount of svtRNA2-1a decreased with low levels being detected at the oldest ages examined.…”

“…30 We found that both the major and minor strands reach in rat/mouse was used for control IP. Total RNA was isolated from the Ago2 and control IPs in three independent experiments and the expression of svtRNA2-1a and miR-16 (used as a positive control) was assessed by rRT-PCR Taqman assays.…”

“…A few Computational analysis of deep sequenced svtRNA2-1a. Small RNAs sequenced from human pre-frontal cortex 30 were obtained from the Gene Expression Omnibus (GEO) database, accession numbers GSM450597-GSM450610. The sequencing reads were pre-processed using the mapper.pl script from the miRDeep2 package 24 with the following options: -a -d -h -j -k TCGTATGCCG -l 18 -m. The RNA secondary structure of svtRNA2-1a and the sequencing read signature and the sequencing read counts across samples were computed using the quantifier.pl script from the same package, using default options.…”

A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing

“…This level of expression placed miR-1839-5p into the top 100 most highly expressed miRNAs in the hippocampus, suggesting it is likely to play an important functional role in this tissue. To identify if the high level of expression of miR-1839-5p is conserved in humans, we examined a recently published human prefrontal cortex deep sequencing data set (Somel et al 2010). Indeed, miR-1839-5p expression was in the top 50 miRNAs in all 12 individuals, ranking between the 22nd and 38th most highly expressed ( Fig.…”