title: 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 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.
authors: Central Arkansas Veterans Healthcare System, North Little Rock GRECC, 2200 Fort Roots Dr. (Bldg. 170, 3J/157), North Little Rock, AR 72114-1706, USA. rdennis@uams.edu
authors: Richard A
authors: RA
authors: Dennis
authors: Beata
authors: B
authors: Przybyla
authors: Cathy
authors: C
authors: Gurley
authors: Patrick M
authors: PM
authors: Kortebein
authors: Pippa
authors: P
authors: Simpson
authors: Dennis H
authors: DH
authors: Sullivan
authors: Charlotte A
authors: CA
authors: Peterson
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D055435:Myostatin; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012146:Rest / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014891:Weight Lifting / Q000502:physiology*
chemical_list: D000199:Actins; D020934:Ciliary Neurotrophic Factor; D018975:Insulin-Like Growth Factor Binding Protein 5; D036341:Intercellular Signaling Peptides and Proteins; C525911:MSTN protein, human; D009124:Muscle Proteins; D055435:Myostatin; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2