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Series GSE72179 Query DataSets for GSE72179
Status Public on Feb 10, 2017
Title Increased activity of canonical NF-kB signaling in muscle fibers alters the satellite cell niche and restrains muscle stem cell function during aging
Organism Mus musculus
Experiment type Expression profiling by array
Summary It has been known for some time that muscle repair potential becomes increasingly compromised with advancing age, and that this age-related defect is associated with reduced activity of muscle satellite cells and with the presence of chronic, low grade inflammation in the muscle. Working from the hypothesis that a heightened inflammatory tone in aged muscle could contribute to poor regenerative capacity, we developed genetic systems to inducibly alter inflammatory gene expression in satellite cells or muscle fibers by modulation of the activity of nuclear factor κB (NF-κB), a master transcriptional regulator of inflammation whose activity is upregulated in many cell types and tissues with age. These studies revealed that activation of NF-κB activity in muscle fibers, but not in satellite cells, drives muscle dysfunction and that lifelong inhibition of NF-κB activity in myofibers preserves muscle regenerative potential with aging via cell-non-autonomous effects on satellite cell function. Further analysis of differential gene expression in muscles with varying NF-κB activity identified a secreted phospholipase (PLA2G5) as a myofiber-expressed NF-κB-regulated gene that governs muscle regenerative capacity with age. Together, these data suggest a model in which NF-κB activation in muscle fibers increases PLA2G5 expression and drives the impairment in regenerative function characteristic of aged muscle. Importantly, inhibition of NF-κB function reverses this impairment, suggesting that FDA-approved drugs, like salsalate, a prodrug form of sodium salicylate, may provide new therapeutic avenues for elderly patients with reduced capacity to recover effectively from muscle injury.
 
Overall design 3 groups of mice: old wild type, young wild type, and old “MISR” mice harboring a transgene that dominantly blocks NF-κB signaling in skeletal muscle via constitutive expression of the IκB super-repressor (ISR) under the muscle fiber-specific muscle creatine kinase (MCK) promoter. There are 2-3 biological replicates per group.
 
Contributor(s) Oh J, Sinha I, Tan KY, Rosner B, Dreyfuss JM, Gjata O, Tran P, Shoelson SE, Wagers AJ
Citation(s) 27852976
Submission date Aug 19, 2015
Last update date Feb 21, 2018
Contact name Jonathan M Dreyfuss
Organization name Joslin Diabetes Center
Department Bioinformatics & Biostatistics Core
Street address 1 Joslin Pl
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (7)
GSM1857107 muscle_old_WT_rep2
GSM1857108 muscle_old_WT_rep3
GSM1857109 muscle_old_MISR_rep1
Relations
BioProject PRJNA293266

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
GSE72179_RAW.tar 67.5 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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