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Aging-US: miRNAs generated from Meg3-Mirg locus are downregulated during aging

07-25-2021

Aging-US published "miRNAs generated from Meg3-Mirg locus are downregulated during aging" which reported that Aging determines a multilevel functional decline and increases the risk for cardiovascular pathologies.

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 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.

In conclusion, this study published in Aging-US, provides new data concerning the mechanisms of natural aging and highlights the robustness of the miRNA modulation during this process.

This study published in Aging-US, provides new data concerning the mechanisms of natural aging and highlights the robustness of the miRNA modulation during this process

Dr. Alexandrina Burlacu from The Institute of Cellular Biology and Pathology “Nicolae Simionescu” said, "Aging is a universal, multifactorial and progressive process determined by an intrinsic decreased ability of the organism to counterbalance the adverse effects of accumulating extrinsic risk factors."

Non-myocytes include multiple cell types, among which the cardiac fibroblasts, which are a heterogeneous and dynamic group of cells with important contributions to cardiac function, in healthy and diseased states.

These findings demonstrate that the cardiac fibroblast is a unique cell type that retains its embryological cardiac identity and has a critical role in the maintenance of the cardiac tissue.

Figure 5. Genes upregulated in aging which are targeted by miRNAs from Meg3-Mirg locus. (A) Venn diagram illustrating the predicted targets of the 27 downregulated miRNAs. Three databases were interrogated and the overlapping targets were further used for pathway enrichment analysis, which identified 347 unique genes. (B) Graphical illustration of the intersection between the unique genes found in KEGG pathway and the upregulated genes identified in Tabula Muris Senis database. The upregulated genes are highlighted in each organ. Itgb2 emerged as the only gene upregulated in 4 out of 6 organs. (C) Illustration of the recognition sites of miRNAs from the locus targeting the 3`UTR region of Itgb2 mRNA. (D) The expression of the Itgb2 in the brain, ventricle, kidney, liver and cultured cardiac fibroblasts. For each organ, the expression is presented relative to the young group. Two-tailed two-samples T-test for equal or unequal variances; Wilcoxon two-sample test for non-normal distribution; * p < 0.05, ** p < 0.01, *** p < 0.001; **** p<0.0001; n=5-10/group.

Aging-related changes in gene expression are more pronounced in cardiac fibroblasts than in other cardiac cells and they mostly affect the inflammation, extracellular matrix organization and angiogenesis.

While miRNAs regulate different aspects of cardiovascular biology, little is known about the extent to which miRNA profile is modulated during aging in cardiac fibroblasts and whether the aging-associated dysregulation of miRNA profile is cell-specific or widespread.

The aims of this study were:

  1. To identify relevant features of the aging-associated miRNA profile in murine cardiac fibroblasts and;
  2. To determine the cell and organ specificity of the aging-associated miRNA changes found in cardiac fibroblasts.

The Burlacu Research Team concluded in their Aging-US Research Output, "this study provides evidence that aging is associated to the downregulation of miRNAs generated by the Meg3-Mirg locus in several cell types and organs. This is likely to be a common and biologically meaningful response in aging, however additional studies are required to determine whether it is universally associated with this process. Such insights may advance the understanding of the mechanisms of aging, being of general interest in the field of geroscience."

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DOI - https://doi.org/10.18632/aging.203208

Full Text - https://www.aging-us.com/article/203208/text

Correspondence to: Alexandrina Burlacu email: sanda.burlacu@icbp.ro

Keywords: aging, miRNA, Meg3-Mirg locus, cardiac fibroblasts, heart ventricles

About Aging-US:

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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