Submitted on March 18, 2008
Revised on July 2, 2008
Accepted on July 27, 2008
Functional deficits and insulin-like growth factor-I gene expression following tourniquet-induced injury of skeletal muscle in young and old rats
David W. Hammers1, Edward K Merritt1, Wayne Matheny2, Martin L. Adamo3, Thomas J. Walters4, J. Scot Estep5, and Roger P Farrar1*
1 University of Texas
2 UTHSC San Antonio
3 University of Texas Health Center at San Antonio
4 US Army Institute of Surgical Research
5 US Army Surgical Research
* To whom correspondence should be addressed. E-mail: rfarrar{at}mail.utexas.edu.
This study investigated the effect of age on recovery of skeletal muscle from an ischemia/reperfusion induced injury. Young (6 month-old) and old (24-27 month-old) Sprague-Dawley rats underwent a 2-hour bout of hind limb 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 post-injury. In addition, old rats demonstrated an attenuated upregulation of IGF-I mRNA and induction of pro-anabolic signaling compared to young in response to injury. We conclude that aged skeletal muscle exhibits more damage and/or defective regeneration following ischemia/reperfusion, and identify an age-associated decrease in local IGF-I responsiveness as a potential mechanism for this phenomenon.
