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% O2levels. 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 / J. Heid, C. Cencioni, R. Ripa, M. Baumgart, S. Atlante, G. Milano, A. Scopece, C. Kuenne, S. Guenther, V. Azzimato, A. Farsetti, G. Rossi, T. Braun, G. Pompilio, F. Martelli, A.M. Zeiher, A. Cellerino, C. Gaetano, F. Spallotta. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:1(2017 Dec), pp. 16839.1-16839.15.
|Titolo:||Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health|
|Settore Scientifico Disciplinare:||Settore MED/11 - Malattie dell'Apparato Cardiovascolare|
|Data di pubblicazione:||dic-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41598-017-16829-w|
|Appare nelle tipologie:||01 - Articolo su periodico|