A nutrigenomics approach for the study of anti-aging interventions: olive oil phenols and the modulation of gene and microRNA expression profiles in mouse brain
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Middle-aged C57Bl/6J mice fed for 6 months with extra-virgin olive oil rich in phenols (H-EVOO, phenol dose/day: 6 mg/kg) showed cognitive and motor improvement compared to controls fed the same olive oil deprived of phenolics (L-EVOO). The aim of the present study was to evaluate whether these behavioral modifications were associated with changes in gene and miRNA expression in the brain.
Two brain areas involved in cognitive and motor processes were chosen: cortex and cerebellum. Gene and miRNA profiling were analyzed by microarray and correlated with performance in behavioral tests.
After 6 months, most of the gene expression changes were restricted to the cerebral cortex. The genes modulated by aging were mainly down-regulated, and the treatment with H-EVOO was associated with a significant up-regulation of genes compared to L-EVOO. Among those, we found genes previously associated with synaptic plasticity and with motor and cognitive behavior, such as Notch1, BMPs, NGFR, GLP1R and CRTC3. The agrin pathway was also significantly modulated. miRNAs were mostly up-regulated in old L-EVOO animals compared to young. However, H-EVOO-fed mice cortex displayed miRNA expression profiles similar to those observed in young mice. Sixty-three miRNAs, out of 1203 analyzed, were significantly down-regulated compared to the L-EVOO group; among them, we found miRNAs whose predicted target genes were up-regulated by the treatment, such as mir-484, mir-27, mir-137, mir-30, mir-34 and mir-124.
We are among the first to report that a dietary intervention starting from middle age with food rich in phenols can modulate at the central level the expression of genes and miRNAs involved in neuronal function and synaptic plasticity, along with cognitive, motor and emotional behavior.
KeywordsAging brain miRNomics Genomics Phenolic compounds Nutraceuticals
The authors thank Prof. Sabrina Giglio and Dr. Marilena Pantaleo for technical support for the scanning of microarray images. The present study was financially supported by the University of Florence and by the Ente Cassa di Risparmio di Firenze. VP at the time of the present experiments was affiliated at the Department of Pharmacology of the University of Florence.
Compliance with ethical standards
Conflict of interest
Each author has made substantial contributions to the conception and design of the study or acquisition of data or analysis and interpretation of data, drafting the article or revising it critically for important intellectual content. Each author has seen and approved the contents of the submitted manuscript. The authors declare that they have no personal or financial interests.
- 2.Valls-Pedret C, Lamuela-Raventos RM et al (2012) Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis 29:773–782Google Scholar
- 3.Giovannelli L (2013) Beneficial effects of olive oil phenols on the aging process: experimental evidence and possible mechanisms of action. Nutr Aging 1:207–223Google Scholar
- 5.D’Angelo S, Manna C et al (2001) Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil. Drug Metab Dispos 29:1492–1498Google Scholar
- 8.Farr SA, Price TO et al (2011) Extra virgin olive oil improves learning and memory in SAMP8 mice. J Alzheimers Dis 28:81–92Google Scholar
- 26.Blalock EM, Chen KC et al (2003) Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment. J Neurosci 23:3807–3819Google Scholar
- 30.Markowska AL, Koliatsos VE et al (1994) Human nerve growth factor improves spatial memory in aged but not in young rats. J Neurosci 14:4815–4824Google Scholar
- 46.Willi R, Winter C et al (2012) Loss of EphA4 impairs short-term spatial recognition memory performance and locomotor habituation. Genes Brain Behav 11:1020–1031Google Scholar
- 47.Li M, Linseman DA et al (2001) Myocyte enhancer factor 2A and 2D undergo phosphorylation and caspase-mediated degradation during apoptosis of rat cerebellar granule neurons. J Neurosci 21:6544–6552Google Scholar