Abstract
MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 558 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since many mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that also function during aging in the human brain.
Highlights
Aging is a complex process that manifests a variety of characteristic and evolutionarily conserved changes
Mouse Brain Small RNA Cloning and Sequencing In order to understand potential contributions of miRNAs to aging processes in the mouse brain, we first examined their expression changes using deep sequencing with Solexa technology. cDNA libraries from small RNAs were prepared from whole brains of young and old mice (5 months and 24–25 months, respectively)
The role of miRNAs in brain aging is only beginning to be uncovered, and here, we provide evidence that multiple miRNAs, including 41 novel miRNA candidates, may be involved in this complex process
Summary
Aging is a complex process that manifests a variety of characteristic and evolutionarily conserved changes. Gene expression profiling studies of the brain have been conducted in mice, rats, chimpanzees, and humans and have shown that specific genes and pathways are affected by aging [6,7,8,9,10]. Studies in mice have reported that genes involved in inflammatory and stress responses, as well as many proteases involved in neuropeptide metabolism, show altered expression [6,9]. How the many affected pathways and processes are regulated and fit into the overall picture of brain aging remain to be elucidated
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