Peripheral circulating exosomal miRNAs potentially contribute to the regulation of molecular signaling networks in aging

People are living longer than ever. Consequently, they have a greater chance for developing a functional impairment or aging-related disease, such as a neurodegenerative disease, later in life. Thus, it is important to identify and understand mechanisms underlying aging as well as the potential for rejuvenation.

Researchers at the University of North Texas Health Science Center used next-generation sequencing to identify differentially expressed microRNAs (miRNAs) in serum exosomes isolated from young (three-month-old) and old (22-month-old) rats and then used bioinformatics to explore candidate genes and aging-related pathways. The researchers identified 2844 mRNAs and 68 miRNAs that were differentially expressed with age. TargetScan revealed that 19 of these miRNAs are predicated to target the 766 mRNAs. Pathways analysis revealed signaling components targeted by these miRNAs: mTOR, AMPK, eNOS, IGF, PTEN, p53, integrins, and growth hormone. In addition, the most frequently predicted target genes regulated by these miRNAs were EIF4EBP1, insulin receptor, PDK1, PTEN, paxillin, and IGF-1 receptor. These signaling pathways and target genes may play critical roles in regulating aging and lifespan, thereby validating our analysis. Understanding the causes of aging and the underlying mechanisms may lead to interventions that could reverse certain aging processes and slow development of aging-related diseases.

Ingenuity Pathway Analysis (IPA) of the differentially expressed miRNAs
in serum exosomes from young and old rats

(A) IPA showing the 22 most significant aging-related pathways involving mRNAs, whose expression is regulated by differentially expressed miRNAs in serum exosomes from young and old rats. Each Z score represents the upregulation or downregulation of gene expression based on young vs. old. The black curve denotes the ratio between the number of the differentially expressed target genes and the total number of genes in each of these pathways. (B) IPA-predicted network for the differentially expressed miRNAs showing predicted targets and their association with biological functions in aging-related signaling pathways governed by the following factors: growth hormone signaling, mammalian target of rapamycin (mTOR) signaling, endothelial nitric oxide synthase (eNOS) signaling, integrin signaling, insulin-like growth factor-1 (IGF-1) signaling, AMP-activated protein kinase (AMPK) signaling, insulin receptor signaling, p53 signaling, and phosphatase and tensin homolog 10 (PTEN) signaling.