Age-related changes in microRNA levels in serum

Hooten, Nicole Noren; Fitzpatrick, Megan J.; Wood, William H.; De, Supriyo; Ejiogu, Ngozi; Zhang, Yongqing; Mattison, Julie A.; Becker, Kevin G.; Zonderman, Alan B.; Evans, Michele K.

doi:10.18632/aging.100603

Cited by 252 publications

(131 citation statements)

References 40 publications

(64 reference statements)

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“…1). Age‐related miRNA expression studies in whole blood (ElSharawy et al ., 2012), PBMCs (Noren Hooten et al ., 2010), and serum (Noren Hooten et al ., 2013; Zhang et al ., 2014) have similarly reported that the majority of age‐related miRNAs show decreased expression in older individuals.…”

Section: Resultsmentioning

confidence: 99%

“…In comparison with previous age‐related miRNA expression studies (Noren Hooten et al ., 2010, 2013; ElSharawy et al ., 2012; Zhang et al ., 2014), our study included > 25 times as many participants ( N = 5221 vs N < 200) and a wide age range (24–92 years). As such, our study was well powered to investigate differential levels of miRNA expression in relation to age.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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SummaryRecent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10−4 (Bonferroni‐corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘microRNA age’ that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10−5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole‐blood microRNA expression profiling. Age‐associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…Total RNA including miRNAs was isolated using the Absolutely RNA miRNA Kit (Agilent) and analyzed using the Agilent Mouse miRNA Microarray 15.0. Microarray was performed and analyzed as previously described (Noren Hooten et al ., 2013). Individual miRNAs with pairwise z‐test P value ≤ 0.05, absolute value of Z ratio ≥ 1.5, with fdr ≤ 0.3 were considered significantly changed.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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SummaryMetformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age‐related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA‐processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post‐transcriptional mechanism involving the RNA‐binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life‐extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR‐20a, miR‐34a, miR‐130a, miR‐106b, miR‐125, and let‐7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1‐dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence‐associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age‐related disease.

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