Functional deficits and insulin-like growth factor-I gene expression following tourniquet-induced injury of skeletal muscle in young and old rats.
This study investigated the effect of age on recovery of skeletal muscle from an ischemia-reperfusion (I/R)-induced injury. Young (6 mo old) and old (24-27 mo old) Sprague-Dawley rats underwent a 2-h bout of hindlimb ischemia induced by a pneumatic tourniquet (TK). The TK was released to allow reperfusion of the affected limb, and animals were divided into 7- and 14-day recovery groups. Maximum plantar flexor force production was assessed in both 7- and 14-day recovery groups of both ages, followed by histological evaluation. Subsequent analysis of IGF-I gene expression and intracellular signaling in 7-day recovery muscles was performed by RT-PCR and Western blotting, respectively. Old rats had significantly greater deficits in force production and exhibited more evidence of histological pathology than young at both 7 and 14 days postinjury. In addition, old rats demonstrated an attenuated upregulation of IGF-I mRNA and induction of proanabolic signaling compared with young in response to injury. We conclude that aged skeletal muscle exhibits more damage and/or defective regeneration following I/R and identify an age-associated decrease in local IGF-I responsiveness as a potential mechanism for this phenomenon.
Hammers
David W
DW
Department of Kinesiology, The University of Texas at Austin, 1 University Station, Austin, TX 78712, USA.
Merritt
Edward K
EK
Matheny
Ronald W
RW
Matheny
Wayne
W
Adamo
Martin L
ML
Walters
Thomas J
TJ
Estep
J Scot
JS
Farrar
Roger P
RP
D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D006614:Hindlimb; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012038:Regeneration; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D015398:Signal Transduction; D013997:Time Factors; D014111:Tourniquets / Q000009:adverse effects
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt