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Inflammatory markers in skeletal muscle of older adults

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Abstract

Older adults have an increase in circulating markers of inflammation. The current study examined whether there is an increase in the expression of inflammatory markers within the vastus lateralis, a major locomotive muscle, of older adults, and if so, whether the reduction in muscle strength and aerobic capacity in older adults is related to increased muscle inflammation. Skeletal muscle biopsies were taken from older adults (n = 17, 67 ± 1.6 years) and young individuals (n = 16, 24 ± 0.6 years) under resting and fasting conditions. Muscle was analyzed for mRNA levels of intracellular inflammatory molecules (MCP1, TNFα and IL-1β) and total cellular protein abundance of cytokines, chemokines and kinases (IL-6, IL-8, MCP1, TNFα, p65 (NF-κB), JNK1/2 and STAT3). MCP1 expression was significantly higher (p < 0.05; 50 %, mRNA and 40 %, protein) in elderly than younger participants, as was IL-8 (4 %). No detectable difference in kinase protein expression was observed for STAT3, JNK or p65 (NF-κB), TNFα or IL-6. Muscle strength was lower in the elderly compared to the young group (1.55 ± 0.17 vs. 2.56 ± 0.13 Nm/kg, p < 0.001). The elderly group also had a significantly lower VO2peak compared to the young group (24.9 ± 1.9 vs. 39.3 ± 1.9, p < 0.001), but muscle strength and VO2peak were not correlated with the examined inflammatory markers. Older adults have increased MCP1 (mRNA and protein abundance) and IL-8 (protein abundance) and also reduced muscle strength and VO2peak. However, the reduction in muscle strength and VO2peak was not related to the increase in muscle inflammatory markers in this cohort.

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Abbreviations

BMI:

Body mass index

IL:

Interleukin

JNK:

c-Jun N-terminal kinases

MAPK:

Mitogen-activated protein kinases

MCP1:

Monocyte chemotactic protein-1

NF-κB:

Nuclear factor kappa-B

STAT:

Signal transducer and activator of transcription

TNFα:

Tumor necrosis factor

VO2peak :

Peak aerobic power

References

  • Antonelli A, Rotondi M, Fallahi P, Ferrari SM, Paolicchi A, Romagnani P, Serio M, Ferrannini E (2006) Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing. Cytokine 34(1–2):32–38

    Article  PubMed  CAS  Google Scholar 

  • Baggiolini M, Dewald B, Moser B (1997) Human chemokines: an update. Ann Rev Imm 15:675–705

    Article  CAS  Google Scholar 

  • Bar-Shai M, Carmeli E, Coleman R, Rozen N, Perek S, Fuchs D, Reznick AZ (2005a) The effect of hindlimb immobilization on acid phosphatase, metalloproteinases and nuclear factor-kappaB in muscles of young and old rats. Mech Ageing Dev 126(2):289–297

    Article  PubMed  CAS  Google Scholar 

  • Bar-Shai M, Carmeli E, Reznick AZ (2005b) The role of NF-kappaB in protein breakdown in immobilization, aging, and exercise: from basic processes to promotion of health. Ann N Y Acad Sci 1057:431–447

    Article  PubMed  CAS  Google Scholar 

  • Bruunsgaard H, Pedersen BK (2003) Age-related inflammatory cytokines and disease. Immunol Allergy Clin North Am 23(1):15–39

    Article  PubMed  Google Scholar 

  • Bruunsgaard H, Andersen-Ranberg K, Hjelmborg JB, Pedersen BK, Jeune B (2003) Elevated levels of tumor necrosis factor alpha and mortality in centenarians. Am J Med 115(4):278–283

    Article  PubMed  CAS  Google Scholar 

  • Buford TW, Cooke MB, Manini TM, Leeuwenburgh C, Willoughby DS (2010) Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men. J Gerontol Series A Bio Sci Med Sci 65(5):532–537

    Article  Google Scholar 

  • Conboy IM, Rando TA (2005) Aging, stem cells and tissue regeneration: lessons from muscle. Cell Cycle 4(3):407–410

    Article  PubMed  CAS  Google Scholar 

  • Degens H (2007) Age-related skeletal muscle dysfunction: causes and mechanisms. J Musculoskelet Neuronal Interact 7(3):246–252

    PubMed  CAS  Google Scholar 

  • Deo R, Khera A, McGuire DK, Murphy SA, Meo Neto Jde P, Morrow DA, de Lemos JA (2004) Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis. J Am Coll Cardiol 44(9):1812–1818

  • Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM, Longo DL (2005) The origins of age-related proinflammatory state. Blood 105(6):2294–2299

    Article  PubMed  CAS  Google Scholar 

  • Fiatarone MA, O’Neill EF, Ryan ND, Clements KM, Solares GR, Nelson ME, Roberts SB, Kehayias JJ, Lipsitz LA, Evans WJ (1994) Exercise training and nutritional supplementation for physical frailty in very elderly people. New Engl J Med 330(25):1769–1775

    Article  PubMed  CAS  Google Scholar 

  • Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, Abellan van Kan G, Andrieu S, Bauer J, Breuille D, Cederholm T, Chandler J, De Meynard C, Donini L, Harris T, Kannt A, Keime Guibert F, Onder G, Papanicolaou D, Rolland Y, Rooks D, Sieber C, Souhami E, Verlaan S, Zamboni M (2011) Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 12(4):249–256

  • Figarella-Branger D, Civatte M, Bartoli C, Pellissier JF (2003) Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies. Muscle Nerve 28(6):659–682

    Article  PubMed  CAS  Google Scholar 

  • Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflammaging an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254

    Article  PubMed  CAS  Google Scholar 

  • Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128(1):92–105

    Article  PubMed  CAS  Google Scholar 

  • Fulda S, Debatin KM (2002) IFNgamma sensitizes for apoptosis by upregulating caspase-8 expression through the Stat1 pathway. Oncogene 21(15):2295–2308

    Article  PubMed  CAS  Google Scholar 

  • Gerli R, Monti D, Bistoni O, Mazzone AM, Peri G, Cossarizza A, Di Gioacchino M, Cesarotti ME, Doni A, Mantovani A, Franceschi C, Paganelli R (2000) Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev 121(1–3):37–46

    PubMed  CAS  Google Scholar 

  • Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovich CF (2001) Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J 15(2):475–482

    Article  PubMed  CAS  Google Scholar 

  • Haddad F, Adams GR (2006) Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophy. J Appl Physiol 100(4):1188–1203

    Article  PubMed  CAS  Google Scholar 

  • Handel ML, McMorrow LB, Gravallese EM (1995) Nuclear factor-kappa B in rheumatoid synovium. Localization of p50 and p65. Arth Rheum 38(12):1762–1770

    Google Scholar 

  • Hughes VA, Frontera WR, Roubenoff R, Evans WJ, Singh MA (2002) Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nut 76(2):473–481

    CAS  Google Scholar 

  • Inadera H, Egashira K, Takemoto M, Ouchi Y, Matsushima K (1999) Increase in circulating levels of monocyte chemoattractant protein-1 with aging. J Interf Cytokine Res 19(10):1179–1182

    Article  CAS  Google Scholar 

  • Janssen I, Heymsfield SB, Wang ZM, Ross R (2000) Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr. J Appl Physiol 89(1):81–88

    PubMed  CAS  Google Scholar 

  • Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Inv 116(6):1494–1505

    Article  CAS  Google Scholar 

  • Kosek DJ, Kim JS, Petrella JK, Cross JM, Bamman MM (2006) Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults. J Appl Physiol 101(2):531–544

    Article  PubMed  CAS  Google Scholar 

  • Krabbe KS, Pedersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Exp Gerontol 39(5):687–699

    Article  PubMed  CAS  Google Scholar 

  • Langen RC, Schols AM, Kelders MC, Van Der Velden JL, Wouters EF, Janssen-Heininger YM (2002) Tumor necrosis factor-alpha inhibits myogenesis through redox-dependent and -independent pathways. Am J Physiol Cell Physiol 283(3):C714–C721

    PubMed  CAS  Google Scholar 

  • Levinger I, Goodman C, Hare DL, Jerums G, Selig S (2007) The effect of resistance training on functional capacity and quality of life in individuals with high and low numbers of metabolic risk factors. Diabetes Care 30(9):2205–2210

    Article  PubMed  Google Scholar 

  • Levinger I, Levinger P, Trenerry MK, Feller JA, Bartlett JR, Bergman N, McKenna MJ, Cameron-Smith D (2011) Increased inflammatory cytokine expression in the vastus lateralis of patients with knee osteoarthritis. Arthr Rheum 63(5):1343–1348

    Article  CAS  Google Scholar 

  • Liu ZG (2003) Adding facets to TNF signaling. The JNK angle. Mol Cell 12(4):795–796

    Article  PubMed  CAS  Google Scholar 

  • Mariani E, Cattini L, Neri S, Malavolta M, Mocchegiani E, Ravaglia G, Facchini A (2006) Simultaneous evaluation of circulating chemokine and cytokine profiles in elderly subjects by multiplex technology: relationship with zinc status. Biogerontol 7(5–6):449–459

    Article  CAS  Google Scholar 

  • Miles EA, Rees D, Banerjee T, Cazzola R, Lewis S, Wood R, Oates R, Tallant A, Cestaro B, Yaqoob P, Wahle KW, Calder PC (2008) Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations. Atheroscl 196(1):298–305

    Article  CAS  Google Scholar 

  • Mylabathula DB, Rice KM, Wang Z, Uddemarri S, Kinnard RS, Blough ER (2006) Age-associated changes in MAPK activation in fast- and slow-twitch skeletal muscle of the F344/NNiaHSD X Brown Norway/BiNia rat model. Exp Gerontol 41(2):205–214

    Article  PubMed  CAS  Google Scholar 

  • Peake J, Della Gatta P, Cameron-Smith D (2010) Aging and its effects on inflammation in skeletal muscle at rest and following exercise-induced muscle injury. Am J Physiol Reg Int Comp Physiol 298(6):R1485–R1495

    Article  CAS  Google Scholar 

  • Phillips T, Leeuwenburgh C (2005) Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J 19(6):668–670

    PubMed  CAS  Google Scholar 

  • Seidler S, Zimmermann HW, Bartneck M, Trautwein C, Tacke F (2010) Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol 11:30

    Article  PubMed  Google Scholar 

  • Shireman PK, Contreras-Shannon V, Ochoa O, Karia BP, Michalek JE, McManus LM (2007) MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration. J Leukoc Biol 81(3):775–785

    Article  PubMed  CAS  Google Scholar 

  • Simon AR, Rai U, Fanburg BL, Cochran BH (1998) Activation of the JAK-STAT pathway by reactive oxygen species. Am J Physiol 275(6 Pt 1):C1640–C1652

    PubMed  CAS  Google Scholar 

  • Thalacker-Mercer AE, Dell’Italia LJ, Cui X, Cross JM, Bamman MM (2010) Differential genomic responses in old vs. young humans despite similar levels of modest muscle damage after resistance loading. Physiol Genomics 40(3):141–149

    Article  PubMed  CAS  Google Scholar 

  • Tidball JG (2005) Inflammatory processes in muscle injury and repair. Am J Physiol Reg Int Comp Physiol 288(2):R345–R353

    Article  CAS  Google Scholar 

  • Toth MJ, Matthews DE, Tracy RP, Previs MJ (2005) Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation. Am J Physiol Endocrinol Metabol 288(5):E883–E891

    Article  CAS  Google Scholar 

  • Trenerry MK, Carey KA, Ward AC, Cameron-Smith D (2007) STAT3 signaling is activated in human skeletal muscle following acute resistance exercise. J Appl Physiol 102(4):1483–1489

    Article  PubMed  CAS  Google Scholar 

  • Trenerry MK, Carey KA, Ward AC, Farnfield MM, Cameron-Smith D (2008) Exercise-induced activation of STAT3 signaling is increased with age. Rejuvenation Res 11(4):717–724

    Article  PubMed  CAS  Google Scholar 

  • Trenerry MK, Della Gatta PA, Larsen AE, Garnham AP, Cameron-Smith D (2010) Impact of resistance exercise training on interleukin-6 and JAK/STAT in young men. Muscle Nerve 43(3):385–392

    Article  PubMed  Google Scholar 

  • Wieczorowska-Tobis K, Niemir ZI, Podkowka R, Korybalska K, Mossakowska M, Breborowicz A (2006) Can an increased level of circulating IL-8 be a predictor of human longevity? Med Sci Monit 12(3):CR118–CR121

    PubMed  CAS  Google Scholar 

  • Williamson D, Gallagher P, Harber M, Hollon C, Trappe S (2003) Mitogen-activated protein kinase (MAPK) pathway activation: effects of age and acute exercise on human skeletal muscle. J Physiol 547(Pt 3):977–987

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was partly funded by the L.E.W Carty Charitable Fund. The authors wish to thank Dr Andrew Garnham (Deakin University) and Dr Mitchell Anderson for performing the muscle biopsies, Dr Paul Della Gatta and Dr Jessica Mathers (Deakin University) for helping with participant recruitment, and all participants for volunteering for this study. Dr Itamar Levinger is a Heart Foundation Postdoctoral Research Fellow (PR 11M 6086).

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia

    Marissa K. Caldow & David Cameron-Smith

  2. Liggins Institute, University of Auckland, Auckland, New Zealand

    David Cameron-Smith

  3. Musculoskeletal Research Centre, La Trobe University, Melbourne, Australia

    Pazit Levinger

  4. Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia

    Pazit Levinger, Michael J. McKenna & Itamar Levinger

  5. School of Sport and Exercise Science, Victoria University, Melbourne, Australia

    Itamar Levinger

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  1. Marissa K. Caldow
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  2. David Cameron-Smith
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  3. Pazit Levinger
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  4. Michael J. McKenna
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  5. Itamar Levinger
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Corresponding author

Correspondence to Itamar Levinger.

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Communicated by Fabio Fischetti.

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Caldow, M.K., Cameron-Smith, D., Levinger, P. et al. Inflammatory markers in skeletal muscle of older adults. Eur J Appl Physiol 113, 509–517 (2013). https://doi.org/10.1007/s00421-012-2458-x

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  • DOI: https://doi.org/10.1007/s00421-012-2458-x

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