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Series GSE23527 Query DataSets for GSE23527
Status Public on Oct 01, 2010
Title Aging and MicroRNA Expression in Human Skeletal Muscle
Organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Summary A common characteristic of aging is the loss of skeletal muscle (sarcopenia) which can lead to falls and fractures. MicroRNAs (miRNA) are novel post-transcriptional modulators of gene expression with a potential role as a regulator of skeletal muscle mass and function. The purpose of this study was to profile miRNA expression patterns in aging human skeletal muscle using a miRNA array followed by in-depth functional and network analysis. Muscle biopsy samples from 36 men (young: 31±2; n=19; older: 73±3; n=17) were: 1) analyzed for the expression of miRNAs using a microRNA array 2) validated with Taqman quantitative real-time PCR assays, and 3) identified (and later validated) for potential gene targets using the bioinformatics knowledge base software, Ingenuity Pathways Analysis. We found that 18 miRNAs were differentially expressed in older humans (P<0.05 and >500 expression level). The Let-7 family members, Let-7b and Let-7e, were significantly elevated and further validated in older subjects (P<0.05). Functional and network analysis from Ingenuity determined that gene targets of the Let-7’s were associated with molecular networks involved in cell cycle control such as cellular proliferation and differentiation. We confirmed with real-time PCR that the mRNA expression of the cell cycle regulators, CDK6, CDC25A and CDC34 were downregulated in older subjects compared to the young (P<0.05). These data suggest that aging is characterized by an increased expression of Let-7 family members which may downregulate genes related to cellular proliferation. We propose that the increased Let-7 expression in older human muscle may be an indicator of impaired cell cycle function.
 
Overall design We analyzed skeletal muscle biopsy samples from 19 young and 17 older male subjects that have participated in our previous and current research experiments. The subjects were not engaged in any regular exercise training at the time of the enrollment; however they were physically independent and overall healthy. Screening of subjects were performed with clinical history, physical exam, and laboratory tests including complete blood count with differential, liver and kidney function tests, coagulation profile, fasting blood glucose and oral glucose tolerance test, hepatitis B and C screening, HIV test, TSH, urinalysis, and drug screening. All subjects gave informed written consent before participating in the study, which was approved by the Institutional Review Board of the University of Texas Medical Branch (which is in compliance with the Declaration of Helsinki). Once recruited, a dual-energy X-ray absorptiometry (DEXA) scan (Hologic QDR 4500W, Bedford, MA) was performed to measure body composition and lean mass.
Study design. All subjects were admitted to the Clinical Research Center the day prior to the experiment, were provided a standardized dinner and were studied following an overnight fast under basal conditions. Subjects were studied during the same time of day to avoid potential circadian changes and refrained from exercise 48h prior to study participation. A muscle biopsy was obtained from the vastus lateralis of the leg. The biopsy was performed using a 5 mm Bergström biopsy needle, under sterile procedure and local anesthesia (1% lidocaine). Muscle biopsy sample was immediately blotted and frozen in liquid nitrogen and stored at -80oC until analysis. The muscle biopsy sample was used for microRNA and gene analysis.
 
Contributor(s) Drummond MJ, McCarthy JJ, Sinha M, Spratt HM, Volpi E, Esser KA, Rasmussen BB
Citation(s) 20876843
Submission date Aug 09, 2010
Last update date Aug 10, 2012
Contact name micah Drummond
E-mail(s) mjdrummo@utmb.edu
Organization name University of Texas Medical Branch
Street address 301 University Boulevard
City Galveston
State/province TX
ZIP/Postal code 77555-1144
Country USA
 
Platforms (2)
GPL10358 LC_MRA-1001_miRHuman_11.0_080411 (miRNA ID version)
GPL10415 LC_MRA-1001_miRHuman_13.0_090309 (miRNA ID version)
Samples (36)
GSM575538 Young_13_Basal
GSM575543 Young_14_Basal
GSM575578 Young_15_Basal
Relations
BioProject PRJNA131783

Download family Format
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE23527_RAW.tar 3.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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