A nutrigenomics approach for the study of anti-aging interventions: olive oil phenols and the modulation of microRNA profiles in mouse brain

We recently demonstrated that EVOO rich in polyphenols , administered to C57Bl/6J mice from middle age to senescence, improved their contextual memory to levels similar to young animals and prevented the age-related impairment in motor coordination (Pitozzi et al., 2012). The aim of the present study was to evaluate whether changes in brain genes and microRNAs expression were associated with the cognitive and motor improvement observed in these mice. Transcriptomics analysis identified 53 genes and 6 gene sets significantly modulated in the mice cortex after 6 months of feeding with the H-EVOO diet, such as Notch1, a synaptic plasticity-related gene and the pathway of agrin, a glycoprotein involved in cholinergic synaptic differentiation and maintenance. Moreover, 63 miRNAs were also differentially expressed in the cortex of H-EVOO mice compared to the L-EVOO group. Mice fed H-EVOO diet showed miRNA expression profiles similar to those observed in young mice, while the L-EVOO mice exhibited profiles very different and, on the contrary, similar to those observed in TgCRND8 mice, a mouse model of Alzheimer's disease (Panel A ) Some of the 63 miRNA found significantly down-regulated comparing H-EVOO to L-EVOO mice have been previously associated to senescence or to neurodegenerative disorders, such as miR101, up-regulated in the cortex of Alzheimer and spinocerebellar ataxia type 1 affected subjects, and miR-34 that gradually increase during brain development and aging and whose improved memory functions in aged mice (Zovoilis et al., 2011). This study may contribute to clarify the mechanisms underlying the health benefits associated with the intake of dietary polyphenols contained in olive oil and support our previous data demonstrating that they were able to counteract age-related dysfunctions.