Characterization of insulin-like growth factor-I gene expression and post-receptor signaling in skeletal muscle following tourniquet-induced ischemia reperfusion injury in young and old mice

Hammers, David Wayne
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Pneumatic tourniquet (TK) use is common during orthopedic surgery, making postoperative recovery from ischemia-reperfusion injury (I/R) a considerable affliction to the elderly. To characterize age-related mechanisms in skeletal muscle I/R recovery, 6- month (young) and 24-month-old (old) C57 B/L mice underwent 2 hours of TK-induced ischemia, followed by 1, 3, 5, or 7 days of recovery. More damage and muscle mass loss was seen in old in response to the I/R injury than young. Old subjects demonstrate both reductions and temporal shifts in total IGF-I, IGF-I Ea, and IGF-I Eb gene expression in the first 7 days compared to the young. Old subjects also show significant reductions in Akt-dependent pro-anabolic signaling (mTOR and FoxO3) through the time course, but were more pronounced at day 7. These data demonstrate that aged skeletal muscle is characterized by more damage and impaired recovery following TK-induced I/R damage, and link the significantly blunted IGF-I expression and signaling during the early course of recovery to this phenomenon.