Altered gene expression of muscle satellite cells contributes to age-related sarcopenia in mice.

BACKGROUND: During aging, muscle tissue undergoes profound changes which lead to a decline in its functional and regenerative capacity. We utilized global gene expression analysis and gene set enrichment analysis to characterize gene expression changes in aging muscle satellite cells.

METHOD: Gene expression data; obtained from Affymetrix Mouse Genome 430 2.0 Array, for 14 mouse muscle satellite cell samples (5 young, 4 middle-aged, and 5 aged), were retrieved from public Gene Expression Omnibus repository. List of differentially expressed genes was generated based on 0.05 multiple-testing-adjusted p-value and 2-fold FC cut-off values. Functional profiling of genes was carried out using PANTHER Classification System.

RESULTS: We have found several differentially expressed genes in satellite cells derived from aged mice compared to young ones. The gene expression changes increased progressively with time, and the majority of the differentially expressed genes were upregulated during aging. While the downregulated genes could not be correlated with specific biological processes the upregulated ones could be associated with muscle differentiation-, inflammation- or fibrosis-related processes. The latter two processes encompass the senescence-associated secretory phenotype for satellite cells which alters the tissue microenvironment and contributes to inflammation and fibrosis observed in aging muscle.

CONCLUSION: Our analysis reveals that by altering gene expression pattern and expressing inflammatory mediators and extracellular matrix components, these cells can directly contribute to muscle wasting in aged mice.