MicroRNAs are small-non coding RNAs of 21-25 bp length that modulate mRNA translation and stability and therefore represent a novel layer in the regulation of gene expression taking place after gene transcription.

Here, we have used next generation sequencing (miRNA-Seq) to quantify expression of microRNAs during aging in the brain of the mouse, of zebrafish and of the short-lived fish Nothobranchius furzeri, an emerging model organism for aging studies.

We sequenced a total of 72 small-RNA libraries derived from individuals of different adult ages and, after identification of differentially-expressed microRNAs and Venn analysis, we identified a small set of microRNAs consistently up- or down-regulated with age in all three species.

Expression changes of selected microRNAs were validated by real-time PCR. We used in situ hybridization to localize microRNAs expression and identified some regulated microRNAs that are either preferentially expressed in the neuronal stem cell niche, or preferentially excluded from the neuronal stem cell niche.

Finally, we investigated the functional impact of these regulated microRNAs by performing gain-of-function experiments in zebrafish embryos. We found that microinjection of some microRNAs that are up-regulated with age induces premature differentiation of neuronal precursors.

Aging is therefore associated with a temporally-extended up-regulation of microRNAs that induce neuronal differentiation and maturation.