CALL FOR PAPERS NextGen Sequencing Technology-based Dissection of Physiological Systems mRNA-Seq reveals complex patterns of gene regulation and expression in the mouse skeletal muscle transcriptome associated with calorie restriction

mRNA-Seq reveals complex patterns of gene regulation and expression in the mouse skeletal muscle transcriptome associated with calorie re- striction. Physiol Genomics 44: 331-344, 2012. First published January 24, 2012; doi:10.1152/physiolgenomics.00129.2011.—Sarcopenia is an age-associated loss of skeletal muscle mass and strength that increases the risk of disability. Calorie restriction (CR), the consumption of fewer calories while maintaining adequate nutrition, mitigates sar- copenia and many other age-related diseases. To identify potential mechanisms by which CR preserves skeletal muscle integrity during aging, we used mRNA-Seq for deep characterization of gene regula- tion and mRNA abundance in skeletal muscle of old mice compared with old mice subjected to CR. mRNA-Seq revealed complex CR- associated changes in expression of mRNA isoforms, many of which occur without a change in total message abundance and thus would not be detected by methods other than mRNA-Seq. Functional anno- tation of differentially expressed genes reveals CR-associated upregu- lation of pathways involved in energy metabolism and lipid biosyn- thesis, and downregulation of pathways mediating protein breakdown and oxidative stress, consistent with earlier microarray-based studies. CR-associated changes not noted in previous studies involved downregu- lation of genes controlling actin cytoskeletal structures and muscle development. These CR-associated changes reflect generally healthier muscle, consistent with CR's mitigation of sarcopenia. mRNA-Seq gen- erates a rich picture of the changes in gene expression associated with CR, and may facilitate identification of genes that are primary medi- ators of CR's effects. deep sequencing; novel transcripts; sarcopenia; aging