nach oben

European Journal of Applied Physiology

Erschienen in:

10.05.2017 | Original Article

Age and sex differences in human skeletal muscle fibrosis markers and transforming growth factor-β signaling

verfasst von: Lewan Parker, Marissa K. Caldow, Rani Watts, Pazit Levinger, David Cameron-Smith, Itamar Levinger

Erschienen in: European Journal of Applied Physiology | Ausgabe 7/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The aim of the study was to determine whether higher fibrosis markers in skeletal muscle of older adults are accompanied by increased expression of components of the canonical TGF-β signal transduction pathway.

Methods

Fourteen healthy young (21–35 years; 9 males and 5 females) and seventeen older (55–75 years; 9 males and 8 females) participants underwent vastus lateralis biopsies to determine intramuscular mRNA and protein expression of fibrogenic markers and TGF-β signaling molecules related to TGF-β1 and myostatin.

Results

Expression of mRNA encoding the pro-fibrotic factors; axin 2, collagen III, β-catenin and fibronectin, were all significantly higher (all p < 0.05) in the older participants (350, 170, 298, and 641%, respectively). Furthermore, axin 2 and β-catenin mRNA were significantly higher in older females than older males (p < 0.05). Gene expression of ActRIIB, myostatin, and TGF-β1 were higher in older adults compared to younger adults (all p < 0.05). There was, however, no difference in the total protein content of myostatin, myoD or myogenin (all p > 0.05), whereas Smad3 protein phosphorylation was 48% lower (p < 0.05) in muscle from older adults.

Conclusions

Increased abundance of mRNA of fibrotic markers was observed in muscle from older adults and was partly accompanied by altered abundance of pro-fibrotic ligands in a sex specific manner.

Atherton PJ, Higginson JM, Singh J, Wackerhage H (2004) Concentrations of signal transduction proteins exercise and insulin responses in rat extensor digitorum longus and soleus muscles. Mol Cell Biochem 261(1–2):111–116CrossRefPubMed

Bamman MM, Hill VJ, Adams GR, Haddad F, Wetzstein CJ, Gower BA, Ahmed A, Hunter GR (2003) Gender differences in resistance-training-induced myofiber hypertrophy among older adults. J Gerontol A Biol Sci Med Sci 58(2):108–116CrossRefPubMed

Beggs ML, Nagarajan R, Taylor-Jones JM, Nolen G, Macnicol M, Peterson CA (2004) Alterations in the TGFbeta signaling pathway in myogenic progenitors with age. Aging Cell 3(6):353–361. doi:10.1111/j.1474-9728.2004.00135.x CrossRefPubMed

Bergstrom J (1962) Muscle electrolytes in man determined by neutron activation analysis on needle biopsy specimens. Scand J Clin Lab Invest 14(Suppl 68):1–110

Brack AS, Rando TA (2007) Intrinsic changes and extrinsic influences of myogenic stem cell function during aging. Stem Cell Rev 3(3):226–237CrossRefPubMed

Buford TW, MacNeil RG, Clough LG, Dirain M, Sandesara B, Pahor M, Manini TM, Leeuwenburgh C (2014) Active muscle regeneration following eccentric contraction-induced injury is similar between healthy young and older adults. J Appl Physiol 116(11):1481–1490. doi:10.1152/japplphysiol.01350.2012 CrossRefPubMed

Caldow MK, Cameron-Smith D, Levinger P, McKenna MJ, Levinger I (2013) Inflammatory markers in skeletal muscle of older adults. Eur J Appl Physiol 113(2):509–517. doi:10.1007/s00421-012-2458-x CrossRefPubMed

Carlson ME, Conboy MJ, Hsu M, Barchas L, Jeong J, Agrawal A, Mikels AJ, Agrawal S, Schaffer DV, Conboy IM (2009) Relative roles of TGF-beta1 and Wnt in the systemic regulation and aging of satellite cell responses. Aging Cell 8(6):676–689. doi:10.1111/j.1474-9726.2009.00517.x CrossRefPubMedCentralPubMed

Charge SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84(1):209–238. doi:10.1152/physrev.00019.2003 CrossRefPubMed

Durieux AC, Amirouche A, Banzet S, Koulmann N, Bonnefoy R, Pasdeloup M, Mouret C, Bigard X, Peinnequin A, Freyssenet D (2007) Ectopic expression of myostatin induces atrophy of adult skeletal muscle by decreasing muscle gene expression. Endocrinology 148(7):3140–3147. doi:10.1210/en.2006-1500 CrossRefPubMed

Evans WJ, Phinney SD, Young VR (1982) Suction applied to a muscle biopsy maximizes sample size. Med Sci Sports Exerc 14(1):101–102PubMed

Ge X, McFarlane C, Vajjala A, Lokireddy S, Ng ZH, Tan CK, Tan NS, Wahli W, Sharma M, Kambadur R (2011) Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts. Cell Res 21(11):1591–1604. doi:10.1038/cr.2011.72 CrossRefPubMedCentralPubMed

Goldspink G, Fernandes K, Williams PE, Wells DJ (1994) Age-related changes in collagen gene expression in the muscles of mdx dystrophic and normal mice. Neuromuscul Disord 4(3):183–191CrossRefPubMed

Haus JM, Carrithers JA, Trappe SW, Trappe TA (2007) Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle. J Appl Physiol 103(6):2068–2076. doi:10.1152/japplphysiol.00670.2007 CrossRefPubMed

Janssen I, Ross R (2005) Linking age-related changes in skeletal muscle mass and composition with metabolism and disease. J Nutr Health Aging 9(6):408–419PubMed

Kirchengast S, Huber J (2009) Gender and age differences in lean soft tissue mass and sarcopenia among healthy elderly. Anthropol Anz 67(2):139–151CrossRefPubMed

Kob R, Fellner C, Bertsch T, Wittmann A, Mishura D, Sieber CC, Fischer BE, Stroszczynski C, Bollheimer CL (2015) Gender-specific differences in the development of sarcopenia in the rodent model of the Aging high-fat rat. J Cachexia Sarcopenia Muscle 6(2):181–191. doi:10.1002/jcsm.12019 CrossRefPubMedCentralPubMed

Kragstrup TW, Kjaer M, Mackey AL (2011) Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging. Scand J Med Sci Sports 21(6):749–757. doi:10.1111/j.1600-0838.2011.01377.x CrossRefPubMed

Leger B, Derave W, De Bock K, Hespel P, Russell AP (2008) Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. Rejuvenation Res 11(1):163–175B. doi:10.1089/rej.2007.0588 CrossRefPubMed

Liu D, Black BL, Derynck R (2001) TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev 15(22):2950–2966. doi:10.1101/gad.925901 CrossRefPubMedCentralPubMed

Marsh DR, Criswell DS, Carson JA, Booth FW (1997) Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats. J Appl Physiol 83(4):1270–1275PubMedCrossRef

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(6):2509–2521. doi:10.1096/fj.11-198663 CrossRefPubMed

McMahon CD, Popovic L, Jeanplong F, Oldham JM, Kirk SP, Osepchook CC, Wong KW, Sharma M, Kambadur R, Bass JJ (2003) Sexual dimorphism is associated with decreased expression of processed myostatin in males. Am J Physiol Endocrinol Metab 284(2):E377–E381. doi:10.1152/ajpendo.00282.2002 CrossRefPubMed

McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387(6628):83–90. doi:10.1038/387083a0 CrossRefPubMed

Mitchell WK, Williams J, Atherton P, Larvin M, Lund J, Narici M (2012) Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol 3:260. doi:10.3389/fphys.2012.00260 CrossRefPubMedCentralPubMed

Morissette MR, Stricker JC, Rosenberg MA, Buranasombati C, Levitan EB, Mittleman MA, Rosenzweig A (2009) Effects of myostatin deletion in aging mice. Aging Cell 8(5):573–583. doi:10.1111/j.1474-9726.2009.00508.x CrossRefPubMedCentralPubMed

Moyer AL, Wagner KR (2011) Regeneration versus fibrosis in skeletal muscle. Curr Opin Rheumatol 23(6):568–573. doi:10.1097/BOR.0b013e32834bac92 CrossRefPubMed

Murakami M, Ohkuma M, Nakamura M (2008) Molecular mechanism of transforming growth factor-beta-mediated inhibition of growth arrest and differentiation in a myoblast cell line. Dev Growth Differ 50(2):121–130. doi:10.1111/j.1440-169X.2007.00982.x CrossRefPubMed

Musaro A, Cusella De Angelis MG, Germani A, Ciccarelli C, Molinaro M, Zani BM (1995) Enhanced expression of myogenic regulatory genes in aging skeletal muscle. Exp Cell Res 221(1):241–248CrossRefPubMed

Oldham JM, Osepchook CC, Jeanplong F, Falconer SJ, Matthews KG, Conaglen JV, Gerrard DF, Smith HK, Wilkins RJ, Bass JJ, McMahon CD (2009) The decrease in mature myostatin protein in male skeletal muscle is developmentally regulated by growth hormone. J Physiol 587(3):669–677. doi:10.1113/jphysiol.2008.161521 CrossRefPubMed

Peterson JM, Guttridge DC (2008) Skeletal muscle diseases, inflammation, and NF-kappaB signaling: insights and opportunities for therapeutic intervention. Int Rev Immunol 27(5):375–387. doi:10.1080/08830180802302389 CrossRefPubMed

Raue U, Slivka D, Jemiolo B, Hollon C, Trappe S (2006) Myogenic gene expression at rest and after a bout of resistance exercise in young (18–30 yr) and old (80–89 yr) women. J Appl Physiol 101(1):53–59. doi:10.1152/japplphysiol.01616.2005 CrossRefPubMed

Rosenberg IH (1997) Sarcopenia: origins and clinical relevance. J Nutr 127(5 Suppl):990S–991SPubMedCrossRef

Sandri M, Barberi L, Bijlsma AY, Blaauw B, Dyar KA, Milan G, Mammucari C, Meskers CG, Pallafacchina G, Paoli A, Pion D, Roceri M, Romanello V, Serrano AL, Toniolo L, Larsson L, Maier AB, Munoz-Canoves P, Musaro A, Pende M, Reggiani C, Rizzuto R, Schiaffino S (2013) Signalling pathways regulating muscle mass in Aging skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway. Biogerontology 14(3):303–323. doi:10.1007/s10522-013-9432-9 CrossRefPubMed

Schafer MJ, Atkinson EJ, Vanderboom PM, Kotajarvi B, White TA, Moore MM, Bruce CJ, Greason KL, Suri RM, Khosla S, Miller JD, Bergen HR 3rd, LeBrasseur NK (2016) Quantification of GDF11 and myostatin in human aging and cardiovascular disease. Cell Metab 23(6):1207–1215. doi:10.1016/j.cmet.2016.05.023 CrossRefPubMedCentralPubMed

Serrano AL, Munoz-Canoves P (2010) Regulation and dysregulation of fibrosis in skeletal muscle. Exp Cell Res 316(18):3050–3058. doi:10.1016/j.yexcr.2010.05.035 CrossRefPubMed

Siriett V, Platt L, Salerno MS, Ling N, Kambadur R, Sharma M (2006) Prolonged absence of myostatin reduces sarcopenia. J Cell Physiol 209(3):866–873. doi:10.1002/jcp.20778 CrossRefPubMed

Suzuki A, Scruggs A, Iwata J (2015) The temporal specific role of WNT/β-catenin signaling during myogenesis. J Nat Sci 1(8):e143PubMedCentralPubMed

Verdijk LB, Snijders T, Drost M, Delhaas T, Kadi F, van Loon LJ (2014) Satellite cells in human skeletal muscle; from birth to old age. Age 36(2):545–547. doi:10.1007/s11357-013-9583-2 CrossRefPubMed

Vogel C, Marcotte EM (2012) Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet 13(4):227–232. doi:10.1038/nrg3185 PubMedCentralPubMedCrossRef

Watts R, McAinch AJ, Dixon JB, O’Brien PE, Cameron-Smith D (2013) Increased Smad signaling and reduced MRF expression in skeletal muscle from obese subjects. Obesity (Silver Spring) 21(3):525–528. doi:10.1002/oby.20070 CrossRef

Welle S, Bhatt K, Shah B, Thornton C (2002) Insulin-like growth factor-1 and myostatin mRNA expression in muscle: comparison between 62–77 and 21–31 yr old men. Exp Gerontol 37(6):833–839CrossRefPubMed

Winbanks CE, Weeks KL, Thomson RE, Sepulveda PV, Beyer C, Qian H, Chen JL, Allen JM, Lancaster GI, Febbraio MA, Harrison CA, McMullen JR, Chamberlain JS, Gregorevic P (2012) Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin. J Cell Biol 197(7):997–1008. doi:10.1083/jcb.201109091 CrossRefPubMedCentralPubMed

Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez-Cadavid NF (2002) Serum myostatin-immunoreactive protein is increased in 60–92 year old women and men with muscle wasting. J Nutr Health Aging 6(5):343–348PubMed

Titel: Age and sex differences in human skeletal muscle fibrosis markers and transforming growth factor-β signaling
verfasst von: Lewan Parker
Marissa K. Caldow
Rani Watts
Pazit Levinger
David Cameron-Smith
Itamar Levinger
Publikationsdatum: 10.05.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Applied Physiology / Ausgabe 7/2017
Print ISSN: 1439-6319
Elektronische ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-017-3639-4

Neu im Fachgebiet Arbeitsmedizin

Das Geschlechterparadoxon in der gesundheitlich beeinträchtigten Lebenszeit – Ende eines Mythos?

Open Access Hüftgelenksbewegungseinschränkung Leitthema

Beginnend mit den 1920er-Jahren hat sich eine Vorstellung über die Geschlechterdifferenzen in Gesundheit und Mortalität etabliert, die von Lorber und Moore in dem einprägsamen Satz: „Women get sicker, but men die quicker“, zusammengefasst wurde [ 1 …, S. 13]. Tatsächlich erscheinen vor dem Hintergrund der höheren Lebenserwartung der Frauen die Studienergebnisse zu den Geschlechterdifferenzen in der Morbidität überraschend, wonach Frauen im Durchschnitt einen schlechteren Gesundheitszustand aufweisen als Männer [

Gesunde Lebenserwartung: Ein kritischer Blick auf Nutzen und Potenziale des demographischen Gesundheitsindikators

Open Access Leitthema

Die demographische Alterung hat vielfältige gesellschaftliche Konsequenzen, deren Ausmaß wesentlich vom Gesundheitszustand der Bevölkerung abhängt. Um diesen analysieren und bewerten zu können, wurden spezielle Kennziffern entwickelt, die in …

Wie hat sich die Lebenserwartung ohne funktionelle Einschränkungen in Deutschland entwickelt? Eine Analyse mit Daten des Deutschen Alterssurveys (DEAS)

Open Access Hüftgelenksbewegungseinschränkung Leitthema

Deutschland erfährt, wie andere Hocheinkommensstaaten, aufgrund kontinuierlich rückläufiger Mortalität und niedriger Geburtenraten tiefgreifende demografische Veränderungen. Der demografische Wandel führt in Deutschland zu einem zunehmend höheren …

Hitzeschutz im Fokus der hessischen Betreuungs- und Pflegeaufsicht

Open Access Klimawandel Übersichtsartikel

Im Sommer 2023 kündigte das Bundesministerium für Gesundheit (BMG) einen nationalen Hitzeschutzplan an und forderte die Länder auf, zu prüfen, „ob die Warnstufen des [Deutschen Wetterdienstes] DWD mit der Durchführung von Akutmaßnahmen …

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Age and sex differences in human skeletal muscle fibrosis markers and transforming growth factor-β signaling

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Arbeitsmedizin

Das Geschlechterparadoxon in der gesundheitlich beeinträchtigten Lebenszeit – Ende eines Mythos?

Gesunde Lebenserwartung: Ein kritischer Blick auf Nutzen und Potenziale des demographischen Gesundheitsindikators

Wie hat sich die Lebenserwartung ohne funktionelle Einschränkungen in Deutschland entwickelt? Eine Analyse mit Daten des Deutschen Alterssurveys (DEAS)

Hitzeschutz im Fokus der hessischen Betreuungs- und Pflegeaufsicht

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2017

Response of women using oral contraception to exercise in the heat

Adaptations in corticospinal excitability and inhibition are not spatially confined to the agonist muscle following strength training

Comparison of the recovery response from high-intensity and high-volume resistance exercise in trained men

Electromyographic evaluation of high-intensity elastic resistance exercises for lower extremity muscles during bed rest

Oral l-menthol reduces thermal sensation, increases work-rate and extends time to exhaustion, in the heat at a fixed rating of perceived exertion

Bilateral differences in muscle fascicle architecture are not related to the preferred leg in jumping athletes

Neu im Fachgebiet Arbeitsmedizin

Das Geschlechterparadoxon in der gesundheitlich beeinträchtigten Lebenszeit – Ende eines Mythos?

Gesunde Lebenserwartung: Ein kritischer Blick auf Nutzen und Potenziale des demographischen Gesundheitsindikators

Wie hat sich die Lebenserwartung ohne funktionelle Einschränkungen in Deutschland entwickelt? Eine Analyse mit Daten des Deutschen Alterssurveys (DEAS)

Hitzeschutz im Fokus der hessischen Betreuungs- und Pflegeaufsicht