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

J. Scott Pattison, Lillian C. Folk, Richard W. Madsen, Thomas E. Childs, Frank W. Booth

Research output: Contribution to journalArticle

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Abstract

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 mo) and old (30-31 mo) rats. Age-related differences were determined using a Student's t-test (α 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; and 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 25 × 20 to 15 × 15, 10 × 10, and 5 × 5 observations, we observed 682, 331, 73, and 3 statistically different mRNAs, 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 high-light new candidate mechanisms that regulate skeletal muscle mass during sarcopenia.

Original languageEnglish (US)
Pages (from-to)34-43
Number of pages10
JournalPhysiological genomics
Volume15
Publication statusPublished - Jan 1 2004

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Keywords

  • Aged
  • Atrophy
  • Microarray
  • Statistics
  • mRNA

ASJC Scopus subject areas

  • Physiology
  • Genetics

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