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1 Health Sciences, Boston Univeristy, Boston, MA, USA
2 Cambridge Genomics Center, Aventis Pharmaceuticals, Cambridge, MA, USA
* To whom correspondence should be addressed. E-mail: skandar{at}bu.edu.
Investigating the molecular mechanisms underlying sarcopenia in humans using microarrays have been complicated by low sample size and the variability inherent in human gene expression profiles. We have conducted a study using Affymetrix GeneChips to identify a molecular signature of aged skeletal muscle. The molecular signature was defined as the set of expressed genes that best distinguished the vastus lateralis muscle of young (n=10) and older (n=12) male subjects, when a k-nearest neighbor supervised classification method was used in conjunction with a signal to noise ratio gene selection method and a hold out cross-validation procedure. The age-specific expression signature was comprised of 45 genes; 27 were upregulated and 18 were downregulated. This signature also correctly classified 75% of the muscle samples from young and older subjects published by an independent laboratory based on their expression profiles. The signature revealed increased expression of several genes involved in mediating cellular responses to inflammation and apoptosis including complement component C1QA, Galectin-1, CEBP-beta, and FOXO3A, among others. The increased expression of genes that regulate pre-mRNA splicing, localization and modification of RNA comprise markers of the aging signature. Downregulated genes in the signature were the glutamine transporter SLC38A1, a TRAF-6 inhibitory zinc finger protein and membrane bound transcription factor protease S2P, among others. The sarcopenia signature developed here will be useful as a molecular model to judge the effectiveness of exercise and other therapeutic treatments aimed at ameliorating the effects of muscle loss associated with aging.
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