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

David W. Hammers, Ronald W. Matheny, Christian Sell, Martin L. Adamo, Thomas J. Walters, J. Scot Estep, Roger P. Farrar

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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 (6. mo) and old (24-28. mo) mice were subjected to 2. h of TK-induced ischemia of the hindlimb followed by 1, 3, 5, or 7. days 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 7. day 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.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalExperimental Gerontology
Volume46
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • FoxO
  • MTOR
  • Muscle regeneration
  • Sarcopenia
  • Tourniquet

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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