Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health

Johanna Heid, Chiara Cencioni, Roberto Ripa, Mario Baumgart, Sandra Atlante, Giuseppina Milano, Alessandro Scopece, Carsten Kuenne, Stefan Guenther, Valerio Azzimato, Antonella Farsetti, Giacomo Rossi, Thomas Braun, Giulio Pompilio, Fabio Martelli, Andreas M. Zeiher, Alessandro Cellerino, Carlo Gaetano, Francesco Spallotta

Research output: Contribution to journalArticle

Abstract

The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-Associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O2 levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis.

Original languageEnglish
Article number16839
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

ASJC Scopus subject areas

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    Heid, J., Cencioni, C., Ripa, R., Baumgart, M., Atlante, S., Milano, G., Scopece, A., Kuenne, C., Guenther, S., Azzimato, V., Farsetti, A., Rossi, G., Braun, T., Pompilio, G., Martelli, F., Zeiher, A. M., Cellerino, A., Gaetano, C., & Spallotta, F. (2017). Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health. Scientific Reports, 7(1), [16839]. https://doi.org/10.1038/s41598-017-16829-w