Research Paper Volume 13, Issue 12 pp 15875—15897
miRNAs generated from Meg3-Mirg locus are downregulated during aging
- 1 Laboratory of Stem Cell Biology, Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest 050568, Romania
- 2 Department of Experimental Therapeutics, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Received: October 31, 2020 Accepted: June 2, 2021 Published: June 22, 2021
https://doi.org/10.18632/aging.203208How to Cite
Copyright: © 2021 Lupan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Aging determines a multilevel functional decline and increases the risk for cardiovascular pathologies. MicroRNAs are recognized as fine tuners of all cellular functions, being involved in various cardiac diseases. The heart is one of the most affected organs in aged individuals, however little is known about the extent and robustness to which miRNA profiles are modulated in cardiac cells during aging. This paper provides a comprehensive characterization of the aging-associated miRNA profile in the murine cardiac fibroblasts, which are increasingly recognized for their active involvement in the cardiac physiology and pathology. Next-generation sequencing of cardiac fibroblasts isolated from young and old mice revealed that an important fraction of the miRNAs generated by the Meg3-Mirg locus was downregulated during aging. To address the specificity of this repression, four miRNAs selected as representative for this locus were further assessed in other cells and organs isolated from aged mice. The results suggested that the repression of miRNAs generated by the Meg3-Mirg locus was a general feature of aging in multiple organs. Bioinformatic analysis of the predicted target genes identified Integrin Beta-2 as an aged-upregulated gene, which was thereafter confirmed in multiple mouse organs. In conclusion, our study provides new data concerning the mechanisms of natural aging and highlights the robustness of the miRNA modulation during this process.