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J Appl Physiol 105: 1274-1281, 2008. First published July 31, 2008; doi:10.1152/japplphysiol.90418.2008
8750-7587/08 $8.00
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Functional deficits and insulin-like growth factor-I gene expression following tourniquet-induced injury of skeletal muscle in young and old rats

David W. Hammers,1 Edward K. Merritt,1 Wayne Matheny,2 Martin L. Adamo,2 Thomas J. Walters,3 J. Scot Estep,4 and Roger P. Farrar1

1Department of Kinesiology, The University of Texas, Austin; 2Department of Biochemistry and the Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health-Science Center at San Antonio, San Antonio; and 3Regenerative Medicine and 4Comparative Pathology, U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas

Submitted 18 March 2008 ; accepted in final form 27 July 2008

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.

aging; insulin-like growth factor-I; ischemia-reperfusion; muscle regeneration; sarcopenia


Address for reprint requests and other correspondence: R. P. Farrar, Dept. of Kinesiology, The Univ. of Texas at Austin, 1 Univ. Station D3700, Austin, TX 78712 (e-mail: rfarrar{at}mail.utexas.edu)






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