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 5´methyl-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.

Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health / Heid, Johanna; Cencioni, Chiara; Ripa, Roberto; Baumgart, Mario; Atlante, Sandra; Milano, Giuseppina; Scopece, Alessandro; Kuenne, Carsten; Guenther, Stefan; Azzimato, Valerio; Farsetti, Antonella; Rossi, Giacomo; Braun, Thomas; Pompilio, Giulio; Martelli, Fabio; M Zeiher, Andreas; Cellerino, Alessandro; Gaetano, Carlo; Spallotta, Francesco. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:(2017). [10.1038/s41598-017-16829-w]

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

Francesco Spallotta
Ultimo
2017

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 5´methyl-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.
2017
Aging; epigenetics; microRNA; cardiovascular; fibroblast
01 Pubblicazione su rivista::01a Articolo in rivista
Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health / Heid, Johanna; Cencioni, Chiara; Ripa, Roberto; Baumgart, Mario; Atlante, Sandra; Milano, Giuseppina; Scopece, Alessandro; Kuenne, Carsten; Guenther, Stefan; Azzimato, Valerio; Farsetti, Antonella; Rossi, Giacomo; Braun, Thomas; Pompilio, Giulio; Martelli, Fabio; M Zeiher, Andreas; Cellerino, Alessandro; Gaetano, Carlo; Spallotta, Francesco. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:(2017). [10.1038/s41598-017-16829-w]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1679222
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