Aging alters gene expression of growth and remodeling factors in human skeletal muscle both at rest and in response to acute resistance exercise - PubMed (original) (raw)

Comparative Study

Aging alters gene expression of growth and remodeling factors in human skeletal muscle both at rest and in response to acute resistance exercise

Richard A Dennis et al. Physiol Genomics. 2008.

Abstract

The purpose of this investigation was to compare expression of genes that function in inflammation and stress, cell structure and signaling, or remodeling and growth in skeletal muscle of young (32 +/- 7 yr, n = 15) and elderly (72 +/- 5 yr, n = 16) healthy subjects before and after a bout of resistance leg exercises. A real-time RT-PCR method was used to screen 100 transcripts in v. lateralis biopsies obtained before and 72 h postexercise. The screen identified 15 candidates for differential expression due to aging and/or exercise that were measured quantitatively. The median levels of four mRNAs (insulin-like growth factor-1 and its binding protein IGFBP5, ciliary neurotrophic factor, and the metallopeptidase MMP2) were significantly affected by aging and were greater (1.6- to 2.3-fold, P </= 0.05) in the young than elderly muscle at both time points. The median levels of three mRNAs were significantly (P </= 0.05) affected by exercise in the young. The metallopeptidase inhibitor TIMP1 and alpha-cardiac actin mRNAs increased 2-fold and 6.5-fold, respectively, and GDF8 (myostatin) mRNA decreased by 50%. However, elderly muscle did not display any significant changes in gene expression postexercise. Thus, aging muscle shows decreased levels at rest and an impaired response to exercise for a number of mRNAs for factors potentially involved in muscle growth and remodeling. Future studies must determine the functional importance of these gene expression changes to protein synthesis, satellite cell activity, and other processes that are directly involved in the mechanisms of muscle hypertrophy.

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Figures

Fig. 1.

Fig. 1.

The effects of aging on the skeletal muscle transcripts for IGF1 (A), ciliary neurotrophic factor (CNTF, B), matrix metallopeptidase (MMP2, C), and IGF binding protein-5 (IGFBP5, D). Data are presented as box plots denoting the medians (line), the 25th and 75th percentiles (boxes), and the 10th and 90th percentiles (whiskers), along with outliers (dots). Between-group significance, with young being greater than elderly, was seen in both pre (white boxes, P ≤0.05)- and post-resistance (gray boxes, P ≤ 0.05) exercise for each transcript. Expression data were determined by quantitative real-time RT-PCR and normalized to 18s rRNA levels.

Fig. 2.

Fig. 2.

The effects of exercise on the median (▲) and individual subject expression (line) of transcripts for tissue inhibitor of metalloproteinase (TIMP1, A), α-cardiac actin isoform (ACTC1, B), and growth and differentiation factor-8 (GDF8, C). Post-exercise (Post-ex) expression was significantly different than pre-exercise (Pre-ex) for the young (P ≤ 0.05) but not the elderly for all 3 genes. Expression data were determined by quantitative real-time RT-PCR and normalized to 18s rRNA levels.

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