Abstract
Purpose
Insulin-like growth factor-1 (IGF-1) regulates protein synthesis and cell cycle kinetics. Given that aging is associated with anabolic resistance, we sought to determine if the attenuated exercise-induced satellite cell (SC) expression in older muscle is associated with a blunted IGF-1 response.
Methods
SC expression (Pax7+ cells) and protein (Western blot) and mRNA (RT-PCR) expression of IGF-1 splice variants and ubiquitous (IGFBP4) and muscle-specific (IGFBP3 and -5) IGF-1 binding proteins were measured in skeletal muscle of young (Y: 22 ± 2, n = 7) and older (O: 70 ± 2, n = 7) adults up to 48 h after an acute bout of resistance exercise.
Results
SC expression was greater in Y compared to O (age; P < 0.01) and increased (interaction; P < 0.05) by 24 h after exercise in Y only. IGF-1Ea and IGF-1Eb mRNA tended to be greater in O (age; P < 0.06–0.09). IGF-1Eb mRNA increased at 48 h (time; P < 0.05), whereas IGF-1Ec mRNA increased (interaction; P < 0.05) at 24 and 48 h in O only. IGF binding protein (IGFBP)4 mRNA was greater (age; P < 0.01) in O with the increase at 24 h and 48 h (time; P < 0.01) primarily driven by changes in O (interaction; P < 0.01). Despite IGFBP3 mRNA being greater in O (age; P < 0.01) and increasing at 48 h (time; P < 0.01), there was no effect of age or exercise on IGFBP3 protein expression. In contrast, IGFBP5 mRNA was greater (age; P < 0.01) despite IGFBP5 protein expression being lower (age; P < 0.01) in O compared to Y.
Conclusions
The greater muscle-specific expression of IGF-1 family members with a blunted post-exercise SC expression may be a compensatory attempt to rescue age-related anabolic resistance.
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Abbreviations
- IGF-1:
-
Insulin-like growth factor-1
- IGFBP:
-
Insulin-like growth factor-1 binding protein
- JAK/STAT:
-
Janus tyrosine kinase/signal transducer and activator of transcription
- mRNA:
-
Messenger ribonucleic acid
- Pax7:
-
Paired box transcription factor 7
- SC:
-
Satellite cells
- SOCS:
-
Suppressor of cytokine signaling
- TBST:
-
Tris-buffered saline with 0.1% Tween
References
Ahtiainen JP, Hulmi JJ, Lehti M, Kraemer WJ, Nyman K, Selanne H, Alen M, Komulainen J, Kovanen V, Mero AA, Philippou A, Laakkonen EK, Hakkinen K (2016) Effects of resistance training on expression of IGF-I splice variants in younger and older men. Eur J Sport Sci 16:1055–1063
Bamman MM, Shipp JR, Jiang J, Gower BA, Hunter GR, Goodman A, McLafferty CL Jr, Urban RJ (2001) Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol Endocrinol Metab 280:E383–E390
Burd NA, Tang JE, Moore DR, Phillips SM (2009) Exercise training and protein metabolism: influences of contraction, protein intake, and sex-based differences. J Appl Physiol (1985) 106:1692–1701
Bushman TL, Kuemmerle JF (1998) IGFBP-3 and IGFBP-5 production by human intestinal muscle: reciprocal regulation by endogenous TGF-beta1. Am J Physiol 275:G1282–G1290
Clemmons DR (2009) Role of IGF-I in skeletal muscle mass maintenance. Trends Endocrinol Metab 20:349–356
Diao Y, Wang X, Wu Z (2009) SOCS1, SOCS3, and PIAS1 promote myogenic differentiation by inhibiting the leukemia inhibitory factor-induced JAK1/STAT1/STAT3 pathway. Mol Cell Biol 29:5084–5093
Ewton DZ, Coolican SA, Mohan S, Chernausek SD, Florini JR (1998) Modulation of insulin-like growth factor actions in L6A1 myoblasts by insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5: a dual role for IGFBP-5. J Cell Physiol 177:47–57
Firth SM, Baxter RC (2002) Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 23:824–854
Fry CS, Drummond MJ, Glynn EL, Dickinson JM, Gundermann DM, Timmerman KL, Walker DK, Dhanani S, Volpi E, Rasmussen BB (2011) Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Skelet Muscle 1:11
Gao S, Durstine JL, Koh HJ, Carver WE, Frizzell N, Carson JA (2017) Acute myotube protein synthesis regulation by IL-6 related cytokines. Am J Physiol Cell Physiol 313:C487–C500. https://doi.org/10.1152/ajpcell.00112.02017
Grubb A, Joanisse S, Moore DR, Bellamy LM, Mitchell CJ, Phillips SM, Parise G (2014) IGF-1 colocalizes with muscle satellite cells following acute exercise in humans. Appl Physiol Nutr Metab 39:514–518
Kim JS, Kosek DJ, Petrella JK, Cross JM, Bamman MM (2005) Resting and load-induced levels of myogenic gene transcripts differ between older adults with demonstrable sarcopenia and young men and women. J Appl Physiol (1985) 99:2149–2158
Kraemer WJ, Ratamess NA, Nindl BC (2017) Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise. J Appl Physiol (1985) 122:549–558
Kuemmerle JF, Teng B (2000) Regulation of IGFBP-4 levels in human intestinal muscle by an IGF-I-activated, confluence-dependent protease. Am J Physiol Gastrointest Liver Physiol 279:G975–G982
Kuemmerle JF, Zhou H (2002) Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates growth and IGF-I secretion in human intestinal smooth muscle by Ras-dependent activation of p38 MAP kinase and Erk1/2 pathways. J Biol Chem 277:20563–20571
Mayhew DL, Kim JS, Cross JM, Ferrando AA, Bamman MM (2009) Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans. J Appl Physiol (1985) 107:1655–1662
McKay BR, O’Reilly CE, Phillips SM, Tarnopolsky MA, Parise G (2008) Co-expression of IGF-1 family members with myogenic regulatory factors following acute damaging muscle-lengthening contractions in humans. J Physiol 586:5549–5560
McKay BR, Ogborn DI, Bellamy LM, Tarnopolsky MA, Parise G (2012) Myostatin is associated with age-related human muscle stem cell dysfunction. FASEB J 26:2509–2521
McKay BR, Ogborn DI, Baker JM, Toth KG, Tarnopolsky MA, Parise G (2013) Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction. Am J Physiol Cell Physiol 304:C717–C728
Nindl BC, Urso ML, Pierce JR, Scofield DE, Barnes BR, Kraemer WJ, Anderson JM, Maresh CM, Beasley KN, Zambraski EJ (2012) IGF-I measurement across blood, interstitial fluid, and muscle biocompartments following explosive, high-power exercise. Am J Physiol Regul Integr Comp Physiol 303:R1080–R1089
Petrella JK, Kim JS, Cross JM, Kosek DJ, Bamman MM (2006) Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women. Am J Physiol Endocrinol Metab 291:E937–E946
Retamales A, Zuloaga R, Valenzuela CA, Gallardo-Escarate C, Molina A, Valdes JA (2015) Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation. Biochem Biophys Res Commun 464:596–602
Roberts MD, Dalbo VJ, Sunderland KL, Poole CN, Hassell SE, Bemben D, Cramer J, Stout J, Kerksick CM (2010) IGF-1 splice variant and IGF-1 peptide expression patterns in young and old human skeletal muscle prior to and following sequential exercise bouts. Eur J Appl Physiol 110:961–969
Rui L, Yuan M, Frantz D, Shoelson S, White MF (2002) SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem 277:42394–42398
Shad BJ, Thompson JL, Breen L (2016) Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review. Am J Physiol Endocrinol Metab 311:E803–E817
Snijders T, Verdijk LB, Smeets JS, McKay BR, Senden JM, Hartgens F, Parise G, Greenhaff P, van Loon LJ (2014) The skeletal muscle satellite cell response to a single bout of resistance-type exercise is delayed with aging in men. Age (Dordr) 36:9699
Snijders T, Nederveen JP, McKay BR, Joanisse S, Verdijk LB, van Loon LJ, Parise G (2015) Satellite cells in human skeletal muscle plasticity. Front Physiol 6:283
Taylor WE, Bhasin S, Artaza J, Byhower F, Azam M, Willard DH Jr, Kull FC Jr, Gonzalez-Cadavid N (2001) Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells. Am J Physiol Endocrinol Metab 280:E221–E228
West DW, Burd NA, Staples AW, Phillips SM (2010) Human exercise-mediated skeletal muscle hypertrophy is an intrinsic process. Int J Biochem Cell Biol 42:1371–1375
Acknowledgements
Study funding provided by a Natural Sciences and Engineering Research Council (NSERC) Discovery Grant to GP. DRM was supported in part by an NSERC Post-Doctoral Fellowship.
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BRM, MAT, and GP designed the research. BRM, MAT, and GP conducted the study. DRM and BRM analyzed the data. DRM wrote the manuscript. All authors read and approved the final manuscript.
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Communicated by William J. Kraemer.
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Moore, D.R., McKay, B.R., Tarnopolsky, M.A. et al. Blunted satellite cell response is associated with dysregulated IGF-1 expression after exercise with age. Eur J Appl Physiol 118, 2225–2231 (2018). https://doi.org/10.1007/s00421-018-3954-4
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DOI: https://doi.org/10.1007/s00421-018-3954-4