High-abundance mRNAs in human muscle: comparison between young and old.

To gain a better understanding of the potential role of altered gene expression in the diminished muscle function in old age, we performed a broad search for transcripts expressed at quantitatively different levels in younger (21-24 yr) and older (66-77 yr) human vastus lateralis muscle by serial analysis of gene expression (SAGE). Because SAGE was based on RNA pooled from muscle of several different subjects, relative concentrations of selected mRNAs also were determined in individual muscle samples by quantitative RT-PCR. There were 702 SAGE tags detected at least 10 times in one or both mRNA pools, and the detection frequency was different (at P < 0.01) between young and older muscle for 89 of these. The ratio of myosin heavy chain 2a mRNA to myosin heavy chain 1 mRNA was reduced in older muscle. The mRNAs encoding several mitochondrial proteins involved in electron transport (including several subunits of cytochrome-c oxidase and NADH dehydrogenase) and subunits of ATP synthase were approximately 30% less abundant in older muscle. Several mRNAs encoding enzymes involved in glucose metabolism also were less abundant in older muscle. Analysis of individual samples revealed that the differences suggested by SAGE were not artifacts of atypical gene expression in one or a few individuals. These data suggest that some of the phenotypic changes in senescent muscle may be related to altered gene transcription.