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Series GSE40936 Query DataSets for GSE40936
Status Public on Jul 31, 2013
Title Metformin mild supplementation improves health and survival of mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Metformin, a commonly used drug prescribed to treat type-2 diabetes, has been found to extend health span and delay cancer incidence and progression. Here, we report that starting chronic treatment with low dose of metformin (0.1% w/w in diet) at one year of age extends health and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with low dose metformin mimicked some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced LDL and cholesterol levels. At a molecular level, metformin increased AMP-activated protein kinase activity without attenuation of the mitochondrial electron transport chain activities. Metformin treatment resulted in lower chronic inflammation and increased antioxidant protection, suggesting that the ability of metformin to improve health of laboratory animals may stem from these factors. Our results support that metformin supplementation could be beneficial in extending health and lifespan in humans.
 
Overall design Groups of one-year old male B6C57/J mice were maintained on ad libitum AIN-93G SD diet, or a 40% caloric restriction of the AIN-93G SD diet, or an ad libitum AIN-93G diet supplemented with 0.1% w/w metformin for the rest of their lives. 5 mice from each of these 3 groups were selected and RNA was extracted from both muscle and liver tissue using 1.0mm glass beads in a Precellys 24 Tissue Homogenizer and Qiagen RNeasy Mini Kits for Fibrous Tissue according to manufacturer's specifications. Quality and quantity of the total RNA was checked with the Agilent 2100 bioanalyzer using RNA 6000 Nano chips. RNA samples were labeled using the Illumina TotalPrep RNA Amplification Kit. In short, 0.5g of total RNA was first converted into single-stranded cDNA with reverse transcriptase using an oligo-dT primer containing the T7 RNA polymerase promoter site and then copied to produce double-stranded cDNA molecules. The double stranded cDNA was cleaned and concentrated with the supplied columns and used in an overnight in-vitro transcription reaction where single-stranded RNA (cRNA) was generated and labeled by incorporation of biotin-16-UTP. Arrays were hybridized using a total of 0.75ug of biotin-labeled cRNA at 58 degrees C for 16 hours to Illumina's Sentrix MouseRef-8 v2 Expression BeadChips. Each BeadChip has ~24,000 well-annotated RefSeq transcripts with approximately 30-fold redundancy. The arrays were washed, blocked and the biotin labeled cRNA was detected by staining with streptavidin-Cy3. Arrays were scanned at a resolution of 0.8um using the Beadstation 500 X from Illumina and the data was extracted using the Illumina GenomeStudio software(v1.6.0). Any spots at or below the background were filtered out using an Illumina detection p value of 0.02 and above. The natural log of all remaining scores were used to find the avg and std of each array and the z-score normalization was calculated and presented below. Z-score = (raw value - avg)/std.
 
Contributor(s) Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin M, Schwab M, Pollak M, Zhang Y, Becker KG, Bohr VA, Ingram DK, Sinclair DA, Wolf NS, Spindler SR, Bernier M, De Cabo R
Citation(s) 23900241
Submission date Sep 17, 2012
Last update date Jun 22, 2020
Contact name Supriyo De
Organization name NIA-IRP, NIH
Department Laboratory of Genetics and Genomics
Lab Computational Biology & Genomics Core
Street address 251 Bayview Blvd
City Baltimore
State/province Maryland
ZIP/Postal code 21224
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (30)
GSM1005301 1-SD-M
GSM1005302 2-SD-M
GSM1005303 3-SD-M
Relations
BioProject PRJNA175396

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE40936.txt.gz 181 b (ftp)(http) TXT
GSE40936_GEO_Supplementary_file_AS_Liver_9-14-12.xls.gz 9.2 Mb (ftp)(http) XLS
GSE40936_GEO_Supplementary_file_AS_Muscle_9-14-12.xlsx.gz 12.7 Mb (ftp)(http) XLSX
GSE40936_RAW.tar 3.1 Mb (http)(custom) TAR
Processed data included within Sample table
Raw data are available on Series record
Raw data included within Sample table

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