title: Impairment of IGF-I expression and anabolic signaling following ischemia/reperfusion in skeletal muscle of old mice.
abstract: With the advancement of age, skeletal muscle undergoes a progressive decline in mass, function, and regenerative capacity. Previously, our laboratory has reported an age-reduction in recovery and local induction of IGF-I gene expression with age following tourniquet (TK)-induced skeletal muscle ischemia/reperfusion (I/R). In this study, young (6 mo) and old (24-28 mo) mice were subjected to 2h of TK-induced ischemia of the hindlimb followed by 1, 3, 5, or 7 days of reperfusion. Real time-PCR analysis revealed clear age-related reductions and temporal alterations in the expression of IGF-I and individual IGF-I Ea and Eb splice variants. ELISA verified a reduction of IGF-I peptide with age following 7 day recovery from TK. Western blotting showed that the phosphorylation of Akt, mTOR, and FoxO3, all indicators of anabolic activity, were reduced in the muscles of old mice. These data indicate that an age-related impairment of IGF-I expression and intracellular signaling does exist following injury, and potentially has a role in the impaired recovery of skeletal muscle with age.
authors.affiliation: Department of Kinesiology, The University of Texas, 1 University Station D3700, Austin, TX 78712, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Hammers
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Matheny
authors.forename: Christian
authors.initials: C
authors.lastname: Sell
authors.forename: Martin L
authors.initials: ML
authors.lastname: Adamo
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walters
authors.forename: J Scot
authors.initials: JS
authors.lastname: Estep
authors.forename: Roger P
authors.initials: RP
authors.lastname: Farrar
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055948:Sarcopenia / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases