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Physiol. Genomics (July 29, 2003). doi:10.1152/physiolgenomics.00040.2003
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Submitted on March 24, 2003
Accepted on July 25, 2003

Transcriptional profiling identifies extensive down regulation of extracellular matrix gene expression in sarcopenic rat soleus muscle

J. Scott Pattison1, Lillian C Folk2, Richard W Madsen3, Thomas E Childs1, and Frank W Booth1*

1 Department of Biomedical Sciences and Pharmacology and Physiology, University of Missouri, Columbia, MO, USA
2 Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
3 Department of Statistics, University of Missouri, Columbia, MO, USA

* To whom correspondence should be addressed. E-mail: boothf{at}missouri.edu.

The direction of change in skeletal muscle mass differs between young and old individuals, growing in young animals and atrophying in old animals. The purpose of the experiment was to develop a statistically conservative list of genes whose expression differed significantly between young growing and old atrophying (sarcopenic) skeletal muscles, which may be contributing to physical frailty. Gene expression levels of >24,000 transcripts were determined in soleus muscle samples from young (3-4 months) and old (30-31 months) rats. Age-related differences were determined using a Students t-test ({alpha} of 0.05) with a Bonferroni-adjustment, which yielded 682 probe sets that differed significantly between young (n=25) and old (n=20) animals. Of 347 total decreases in aged/sarcopenic muscle relative to young muscles, 199 were functionally identified; the major theme being that 24% had a biological role in the extracellular matrix and cell adhesion. Three themes were observed from 213 of the 335 total increases in sarcopenic muscles whose functions were documented in databases: 1) 14% are involved in immune response, 2) 9% play a role in proteolysis, ubiquitin-dependent degradation, and proteasome components, 3) 7% act in stress/antioxidant responses. A total of 270 differentially expressed genes and ESTs had unknown/unclear functions. By decreasing the sample sizes of young and old animals from 25x20 to 15x15, 10x10, and 5x5 observations; 682, 331, 73, and 3 statistically different mRNAs were observed, respectively. Use of large sample size and a Bonferroni multiple testing adjustment in combination yielded increased statistical power, while protecting against false positives. Finally, multiple mRNAs that differ between young growing and old, sarcopenic muscles were identified and may highlight new candidate mechanisms that regulate skeletal muscle mass during sarcopenia.




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