Impairment of IGF-I expression and anabolic signaling following ischemia/reperfusion in skeletal muscle of old mice

With the advancement of age, skeletal muscle undergoes a progressive decline in mass, function, and regenerative capacity. Previously, our laboratory has reported an age-reduction in recovery and local induction of IGF-I gene expression with age following tourniquet (TK)-induced skeletal muscle ischemia/reperfusion (I/R). In this study, young (6mo) and old (24–28mo) mice were subjected to 2h of TK-induced ischemia of the hindlimb followed by 1, 3, 5, or 7days of reperfusion. Real time-PCR analysis revealed clear age-related reductions and temporal alterations in the expression of IGF-I and individual IGF-I Ea and Eb splice variants. ELISA verified a reduction of IGF-I peptide with age following 7day recovery from TK. Western blotting showed that the phosphorylation of Akt, mTOR, and FoxO3, all indicators of anabolic activity, were reduced in the muscles of old mice. These data indicate that an age-related impairment of IGF-I expression and intracellular signaling does exist following injury, and potentially has a role in the impaired recovery of skeletal muscle with age. ► Aging muscle incurs greater damage following ischemia/reperfusion than in young. ► IGF-I expression in both peptide and mRNA of IGF-I were reduced in aging. ► Anabolic activity of aged muscle subsequent to injury was reduced compared to young. ► Aging reduced phosphorylation of intermediates of the PI3 Kinase pathway in muscle. ► Altered IGF-I signaling in aging muscle impairs recovery.