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Physiol. Genomics (December 11, 2007). doi:10.1152/physiolgenomics.00191.2007
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Submitted on August 16, 2007
Accepted on December 6, 2007

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 Dennis1*, Beata Przybyla2, Cathy Gurley2, Patrick M Kortebein3, Pippa Simpson4, Dennis H Sullivan5, and Charlotte A. Peterson6

1 GRECC, Central Arkansas Veterans Healthcare System, North Little Rock, Arkansas, United States; Geriatrics, University of Arkansas for Medical Sciences, Arkansas, United States
2 Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
3 GRECC, Central Arkansas Veterans Healthcare System, North Little Rock, Arkansas, United States; Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States; Physical Medicine and Rehabilitation, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
4 Pediatrics and Quantitative Health Sciences, Children's Research Institute, Milwaukee, Wisconsin, United States
5 GRECC, Central Arkansas Veterans Healthcare System, North Little Rock, Arkansas, United States; Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
6 College of Health Sciences, University of Kentucky, Lexington, Kentucky, United States

* To whom correspondence should be addressed. E-mail: rdennis{at}uams.edu.

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±7yrs, N=15) and elderly (72±5yrs, N=16) healthy subjects before and after a bout of resistance leg exercises. A real-time RTPCR method was used to screen 100 transcripts in v. lateralis biopsies obtained before and 72 hours post-exercise. 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 α-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 post-exercise. 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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