Influence of age, sex, and strength training on human muscle gene expression determined by microarray

Abstract

The purpose of this study was to determine the influence of age, sex, and strength training (ST) on large-scale gene expression patterns in vastus lateralis muscle biopsies using high-density cDNA microarrays and quantitative PCR. Muscle samples from sedentary young (20-30 yr) and older (65-75 yr) men and women (5 per group) were obtained before and after a 9-wk unilateral heavy resistance ST program. RNA was hybridized to cDNA filter microarrays representing approximately 4,000 known human genes and comparisons were made among arrays to determine differential gene expression as a result of age and sex differences, and/or response to ST. Sex had the strongest influence on muscle gene expression, with differential expression (>1.7-fold) observed for approximately 200 genes between men and women (approximately 75% with higher expression in men). Age contributed to differential expression as well, as approximately 50 genes were identified as differentially expressed (>1.7-fold) in relation to age, representing structural, metabolic, and regulatory gene classes. Sixty-nine genes were identified as being differentially expressed (>1.7-fold) in all groups in response to ST, and the majority of these were downregulated. Quantitative PCR was employed to validate expression levels for caldesmon, SWI/SNF (BAF60b), and four-and-a-half LIM domains 1. These significant differences suggest that in the analysis of skeletal muscle gene expression issues of sex, age, and habitual physical activity must be addressed, with sex being the most critical variable.

Fig. 1

Microarray (GF211) and quantitative PCR (qPCR) expression data are presented for three genes used in the microarray validation experiments. BAF60b, SWI/SNF; FHL1, four-and-a-half LIM domains 1; CALD, caldesmon; ST, strength training. For the microarray results, data are intensity values averaged for men and women baseline (before-ST) samples as used in Tables 3–6. For the qPCR results, data are means with SE for relative expression levels (arbitrary units). Caldesmon data are shown at 1/10 actual values for the microarray intensity data. For the microarray data, women demonstrated greater than twofold higher expression than men for all three genes. *Significantly lower expression in men compared with women for the qPCR data (P ≤ 0.06; see RESULTS).