title: Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis.
abstract: The ability of skeletal muscle to hypertrophy in response to a growth stimulus is known to be compromised in older individuals. We hypothesized that a change in the expression of protein-encoding genes in response to a hypertrophic stimulus contributes to the blunted hypertrophy observed with aging. To test this hypothesis, we determined gene expression by microarray analysis of plantaris muscle from 5- and 25-mo-old mice subjected to 1, 3, 5, 7, 10, and 14 days of synergist ablation to induce hypertrophy. Overall, 1,607 genes were identified as being differentially expressed across the time course between young and old groups; however, the difference in gene expression was modest, with cluster analysis showing a similar pattern of expression between the two groups. Despite ribosome protein gene expression being higher in the aged group, ribosome biogenesis was significantly blunted in the skeletal muscle of aged mice compared with mice young in response to the hypertrophic stimulus (50% vs. 2.5-fold, respectively). The failure to upregulate pre-47S ribosomal RNA (rRNA) expression in muscle undergoing hypertrophy of old mice indicated that rDNA transcription by RNA polymerase I was impaired. Contrary to our hypothesis, the findings of the study suggest that impaired ribosome biogenesis was a primary factor underlying the blunted hypertrophic response observed in skeletal muscle of old mice rather than dramatic differences in the expression of protein-encoding genes. The diminished increase in total RNA, pre-47S rRNA, and 28S rRNA expression in aged muscle suggest that the primary dysfunction in ribosome biogenesis occurs at the level of rRNA transcription and processing.
authors.affiliation: Center for Muscle Biology, University of Kentucky, Lexington, Kentucky; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky;
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Kirby
authors.affiliation: Center for Muscle Biology, University of Kentucky, Lexington, Kentucky; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky; Department of Molecular and Integrative Physiology, Medical School, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Jonah D
authors.initials: JD
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky;
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: England
authors.affiliation: Center for Muscle Biology, University of Kentucky, Lexington, Kentucky; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Chaillou
authors.affiliation: Center for Muscle Biology, University of Kentucky, Lexington, Kentucky; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky;
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Esser
authors.affiliation: Center for Muscle Biology, University of Kentucky, Lexington, Kentucky; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky; jjmcca2@uky.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: McCarthy
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006984:Hypertrophy; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000096:biosynthesis* / Q000235:genetics; D012339:RNA, Ribosomal, 28S / Q000096:biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D004275:DNA, Ribosomal; D012335:RNA, Ribosomal; D012339:RNA, Ribosomal, 28S
keywords: age; hypertrophy; microarray; ribosome biogenesis; skeletal muscle