microRNA Expression Patterns Reveal Differential Expression of Target Genes with Age

Abstract

Recent evidence supports a role for microRNAs (miRNAs) in regulating the life span of model organisms. However, little is known about how these small RNAs contribute to human aging. Here, we profiled the expression of over 800 miRNAs in peripheral blood mononuclear cells from young and old individuals by real-time RT-PCR analysis. This genome-wide assessment of miRNA expression revealed that the majority of miRNAs studied decreased in abundance with age. We identified nine miRNAs (miR-103, miR-107, miR-128, miR-130a, miR-155, miR-24, miR-221, miR-496, miR-1538) that were significantly lower in older individuals. Among them, five have been implicated in cancer pathogenesis. Predicted targets of several of these miRNAs, including PI3 kinase (PI3K), c-Kit and H2AX, were found to be elevated with advancing age, supporting a possible role for them in the aging process. Furthermore, we found that decreasing the levels of miR-221 was sufficient to cause a corresponding increase in the expression of the predicted target, PI3K. Taken together, these findings demonstrate that changes in miRNA expression occur with human aging and suggest that miRNAs and their predicted targets have the potential to be diagnostic indicators of age or age-related diseases.

Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence

“…We hypothesized that changes in DICER1 levels may contribute to the age‐associated decline in miRNAs (Noren Hooten et al ., 2010). Therefore, we examined DICER1 mRNA levels by reverse transcription (RT) followed by real‐time quantitative (q)PCR analysis from PBMCs from young (~30 year old) and older (~64 year old) individuals and found a significant decrease in DICER1 mRNA levels with human age (Fig.…”

“…Furthermore, aged mouse adipocytes also have lower DICER1 levels (Mori et al ., 2012). Here, we found that DICER1 mRNA levels decreased with age in human PBMCs, which may provide a mechanism for lower miRNA levels we previously observed in this cell population in the same cohort of individuals (Noren Hooten et al ., 2010). …”

“…1A, a subcohort of young (30 years) and older (64 years) participants from the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS) (Evans et al ., 2010) were chosen for examination of DICER1 and DROSHA mRNA levels with age. Clinical information on this subcohort has been described previously and is also listed in Table 1A ( n  = 14/group) (Noren Hooten et al ., 2010) and explained in the Supporting Information. DICER1 levels were quantified from PBMCs by RT–qPCR analysis as described below and in Supporting Information.…”

“…Additionally, dicer loss‐of‐function mutations in Caenorhabditis elegans reduce lifespan and homeostatic stress responses (Mori et al ., 2012). We reported that miRNA levels decrease with advancing age in human peripheral blood mononuclear cells (PBMCs) and primate skeletal muscle, while others have found decreased levels of miRNAs with age in mouse brain and in C. elegans (Noren Hooten et al ., 2010, 2013; Smith‐Vikos & Slack, 2012; Mercken et al ., 2013). Given the conservation of miRNAs across species, and that a single miRNA can regulate C. elegans lifespan and predict the mortality of individual C. elegans (Smith‐Vikos & Slack, 2012), it is likely that miRNAs play an important role in regulating lifespan in humans and other species.…”

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

“…In humans, highly specific miRNA expression patterns are correlated with many age‐related diseases including cardiovascular disease (Small & Olson, 2011; Huan et al ., 2015c) and cancer (Lu et al ., 2005; Hayes et al ., 2014). Recent studies have examined differentially expressed miRNAs in relation to age in whole blood (ElSharawy et al ., 2012), peripheral blood mononuclear cells (PBMC) (Noren Hooten et al ., 2010), and serum (Noren Hooten et al ., 2013; Zhang et al ., 2014). These studies, however, were based on small sample sizes, limiting the power to investigate age‐related changes in miRNA expression.…”