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

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 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 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.

Exercise-induced regulation of matrix metalloproteinases in the skeletal muscle of subjects with type 2 diabetes

“…32 However, in other tissue, there appears to be a stronger relationship between age and MMP dysregulation. 28,34 In cardiac tissue, exercise training seemingly protects against age-associated reductions in active MMP-1, MMP-2 and MT1-MMP in a rodent model. Regular physical activity attenuates elevations in TIMP-1 that were detected in aging versus young rats.…”

Relation between extent of myostatin depletion and muscle growth in mature mice

“…results suggest that adult muscles have ϳ2-3 times the minimum concentration of myostatin that is needed to restrain muscle growth. Thus, a modest reduction in myostatin expression, such as the reduction often observed after exercise (8,12,14,15,24,31,37), might not be sufficient to promote muscle hypertrophy by itself. This conclusion is supported by the observation that many subjects with reduced (ϳ50%) myostatin expression after strength training do not have muscle fiber hypertrophy (15).…”

“…For example, several studies have demonstrated that resistance training reduces myostatin expression generally in the 20 -50% range (8,12,14,15,24,31,37). One of these studies indicated that the increase in muscle mass induced by such exercise correlated with the magnitude of suppression of myostatin mRNA expression (12), whereas another study did not support such a correlation (15).…”

Follistatin: A Novel Therapeutic for the Improvement of Muscle Regeneration

“…a-Cardiac actin (Actc1) expression has been shown to be regulated during muscle regeneration following trauma from pathologic diseases that appears characteristic of activated satellite cells and regenerating myofibers (Dennis et al, 2008). On day 10, Actc1 was significantly increased with both the high-and low-frequency doses of FST, whereas on day 14 it was only significant with the high-frequency dose, producing a 3.7-fold increase (Fig.…”