Possible Link Between Aging and Mesenchymal Stem Cell Exosomal Mirna
Year: 2017
Type: conference-abstract
Abstract: Aging is a complex phenomenon with the number of contributing biological factors. Recently, important links have been reported between microRNAs (miRNA) and aging. miRNAs are short, non-coding RNAs that induce mRNA degradation or repression post-transcriptionally and thus affect a number of biological processes including stem cell maintenance, proliferation and metabolism. It is well established that for cell-cell and cell-tissue interaction, miRNAs are transported as cargo in exosomes. To identify specific differences between miRNA from young-adult (6 week C57BL/6 mice) and aged (78 week) mesenchymal stem cells (MSCs), we performed microarray analysis of exosomal miRNAs and found that a number of biologically relevant miRNAs were differentially expressed. miR-370 was overexpressed (4.49 fold) in exosomes from the older animals. miR-370 has been implicated in cholesterol homeostasis, fatty acid metabolism and lipogenesis. miR-214 was overexpressed (2.7 fold) in exosomes of old MSCs. miR-214 represses Wnt signaling which regulates adipogenesis. This may explain the possible shift of MSCs differentiation tendency from the osteoblast to the adipocyte lineage; such a shift is also reported in aging-related diseases. In addition, we investigated the effect of aging on the function of exosomes. MSCs from young-adult and aged animals were exposed to hypoxic (2% oxygen) conditions and exosomes isolated. Under hypoxic conditions, tubule formation induced by exosomes from young-adult animals was greater than that from the older group (p=1e-7). Thus, age-associated differences in miRNA expression may account, in part, for age associated differences in fatty acid metabolism, body composition, and the ability to respond to a hypoxic stress.
Source: Innovation in Aging
Institutions: Cedars-Sinai Medical Center, Johns Hopkins University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,977
OpenAlex ID: W2733242810