Impairment of IGF-I Expression and Anabolic Signaling Following Ischemia/reperfusion in Skeletal Muscle of Old Mice

Overview

Journal Exp Gerontol

Specialty Geriatrics

Date 2010 Nov 25

PMID 21094246

Citations 12

Authors

David W Hammers

Ronald W Matheny Jr

Christian Sell

Martin L Adamo

Thomas J Walters

J Scot Estep

Roger P Farrar

Affiliations

Soon will be listed here.

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 2h 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.

Citing Articles

Vascular dysfunction as a potential culprit of sarcopenia.

Jeon Y, Shin M, Saini S, Custodero C, Aggarwal M, Anton S Exp Gerontol. 2020; 145:111220.

PMID: 33373710 PMC: 8168450. DOI: 10.1016/j.exger.2020.111220.

Crosstalk of Hedgehog and mTORC1 Pathways.

Larsen L, Moller L Cells. 2020; 9(10).

PMID: 33081032 PMC: 7603200. DOI: 10.3390/cells9102316.

Aging Exacerbates Ischemia-Reperfusion-Induced Mitochondrial Respiration Impairment in Skeletal Muscle.

Paradis S, Charles A, Georg I, Goupilleau F, Meyer A, Kindo M Antioxidants (Basel). 2019; 8(6).

PMID: 31181751 PMC: 6616544. DOI: 10.3390/antiox8060168.

An optimized low-pressure tourniquet murine hind limb ischemia reperfusion model: Inducing acute ischemia reperfusion injury in C57BL/6 wild type mice.

Drysch M, Wallner C, Schmidt S, Reinkemeier F, Wagner J, Lehnhardt M PLoS One. 2019; 14(1):e0210961.

PMID: 30677066 PMC: 6345480. DOI: 10.1371/journal.pone.0210961.

Controlled delivery of SDF-1α and IGF-1: CXCR4(+) cell recruitment and functional skeletal muscle recovery.

Rybalko V, Pham C, Hsieh P, Hammers D, Merscham-Banda M, Suggs L Biomater Sci. 2015; 3(11):1475-86.

PMID: 26247892 PMC: 5494972. DOI: 10.1039/c5bm00233h.

References

Foster A, Carlson B . Myotoxicity of local anesthetics and regeneration of the damaged muscle fibers. Anesth Analg. 1980; 59(10):727-36. View

Yang S, Goldspink G . Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Lett. 2002; 522(1-3):156-60. DOI: 10.1016/s0014-5793(02)02918-6. View

Owino V, Yang S, Goldspink G . Age-related loss of skeletal muscle function and the inability to express the autocrine form of insulin-like growth factor-1 (MGF) in response to mechanical overload. FEBS Lett. 2001; 505(2):259-63. DOI: 10.1016/s0014-5793(01)02825-3. View

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

Matheny Jr R, Adamo M . Role of Akt isoforms in IGF-I-mediated signaling and survival in myoblasts. Biochem Biophys Res Commun. 2009; 389(1):117-21. PMC: 2756470. DOI: 10.1016/j.bbrc.2009.08.101. View

Hill M, Wernig A, Goldspink G . Muscle satellite (stem) cell activation during local tissue injury and repair. J Anat. 2003; 203(1):89-99. PMC: 1571137. DOI: 10.1046/j.1469-7580.2003.00195.x. View

Zhao J, Brault J, Schild A, Cao P, Sandri M, Schiaffino S . FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 2007; 6(6):472-83. DOI: 10.1016/j.cmet.2007.11.004. View

Hammers D, Merritt E, Matheny Jr R, Matheny W, Adamo M, Walters T . Functional deficits and insulin-like growth factor-I gene expression following tourniquet-induced injury of skeletal muscle in young and old rats. J Appl Physiol (1985). 2008; 105(4):1274-81. PMC: 2576024. DOI: 10.1152/japplphysiol.90418.2008. View

Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P . FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007; 6(6):458-71. DOI: 10.1016/j.cmet.2007.11.001. View

10.

Carlson B, Faulkner J . Muscle transplantation between young and old rats: age of host determines recovery. Am J Physiol. 1989; 256(6 Pt 1):C1262-6. DOI: 10.1152/ajpcell.1989.256.6.C1262. View

11.

Matheny Jr R, Nindl B, Adamo M . Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration. Endocrinology. 2010; 151(3):865-75. PMC: 2840678. DOI: 10.1210/en.2009-1217. View

12.

Coolican S, Samuel D, Ewton D, McWade F, FLORINI J . The mitogenic and myogenic actions of insulin-like growth factors utilize distinct signaling pathways. J Biol Chem. 1997; 272(10):6653-62. DOI: 10.1074/jbc.272.10.6653. View

13.

Conboy I, Rando T . Aging, stem cells and tissue regeneration: lessons from muscle. Cell Cycle. 2005; 4(3):407-10. DOI: 10.4161/cc.4.3.1518. View

14.

Musaro A, Giacinti C, Borsellino G, Dobrowolny G, Pelosi L, Cairns L . Stem cell-mediated muscle regeneration is enhanced by local isoform of insulin-like growth factor 1. Proc Natl Acad Sci U S A. 2004; 101(5):1206-10. PMC: 337031. DOI: 10.1073/pnas.0303792101. View

15.

Lee S, Barton E, Sweeney H, Farrar R . Viral expression of insulin-like growth factor-I enhances muscle hypertrophy in resistance-trained rats. J Appl Physiol (1985). 2004; 96(3):1097-104. DOI: 10.1152/japplphysiol.00479.2003. View

16.

Pelosi L, Giacinti C, Nardis C, Borsellino G, Rizzuto E, Nicoletti C . Local expression of IGF-1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines. FASEB J. 2007; 21(7):1393-402. DOI: 10.1096/fj.06-7690com. View

17.

Sengupta A, Molkentin J, Yutzey K . FoxO transcription factors promote autophagy in cardiomyocytes. J Biol Chem. 2009; 284(41):28319-28331. PMC: 2788882. DOI: 10.1074/jbc.M109.024406. View

18.

Adamo M, Farrar R . Resistance training, and IGF involvement in the maintenance of muscle mass during the aging process. Ageing Res Rev. 2006; 5(3):310-31. DOI: 10.1016/j.arr.2006.05.001. View

19.

McLoughlin T, Smith S, DeLong A, Wang H, Unterman T, Esser K . FoxO1 induces apoptosis in skeletal myotubes in a DNA-binding-dependent manner. Am J Physiol Cell Physiol. 2009; 297(3):C548-55. PMC: 2740395. DOI: 10.1152/ajpcell.00502.2008. View

20.

Adams G, McCue S . Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats. J Appl Physiol (1985). 1998; 84(5):1716-22. DOI: 10.1152/jappl.1998.84.5.1716. View