Association of insulin-like growth factor mRNA expressions with muscle regeneration in young, adult, and old rats.

The purpose of this study was to determine whether impaired regeneration of skeletal muscle in old rats can be attributed to diminished expression of insulin-like growth factor (IGF) mRNAs. Fischer 344 male rats aged 2 (young), 12 (adult), and 24 mo (old) were given an injection of the myotoxic anesthetic, bupivacaine, into the left tibialis anterior muscle. Muscle mass and protein concentration recovered to contralateral control values by 28 days in young, but not adult or old rats. The temporal and maximal expressions of IGF-I mRNA were similar during recovery from bupivacaine on days 5 and 10 in young, adult, and old rat muscles. IGF-I mRNA levels were reduced toward control levels in young rats by 15 days, but remained elevated in adult and old rats. IGF-I receptor mRNA in bupivacaine-injected muscle of old rats was elevated significantly higher than injected muscle of young and adult rats at recovery day 5. Five days after bupivacaine injection, IGF-II mRNA was increased 46-fold in young rats but was only increased fourfold in adult rats. Thereafter, IGF-II mRNA expression was similar for young, adult, and old rats at 10 and 15 days of recovery. In summary, we demonstrate that impaired regeneration of the tibialis anterior muscle in adult or old rats after bupivacaine-induced damage is associated with a prolonged elevation of IGF-I mRNA expression and/or diminished initial IGF-II mRNA expression.