Aging Clinical and Experimental Research

, Volume 24, Issue 5, pp 412–422 | Cite as

Potential mechanisms underlying the role of chronic inflammation in age-related muscle wasting

  • Edward Jo
  • Sang-Rok Lee
  • Bong-Sup Park
  • Jeong-Su KimEmail author
Review Article


Sarcopenia, an age-related condition characterized by progressive skeletal muscle degeneration, might exist as one of the primary clinical conditions underlying severe functional impairment as well as increased risk of co-morbidities in the elderly. Although the etiology of sarcopenia remains multifaceted, age-related chronic inflammation has been strongly implicated in muscle wasting and related sequelae during advanced age. Recent evidence suggests that aberrant, unresolved alterations in regular inflammatory processes during advanced age might ultimately operate as the link that drives skeletal muscle to become more degenerative and dysfunctional in nature. Such negative atrophic muscular outcomes might result from inflammation-induced disruption of central mechanisms regulating skeletal muscle morphology and remodeling. In addition, recent findings demonstrate an adverse confluence between sarcopenia and excessive adiposity (i.e. sarcopenic obesity), as the co-existence of such adverse alterations in body composition may exacerbate systemic inflammation and muscle wasting in the elderly. The following evidence-based review serves to examine sarcopenia from a mechanistic perspective with emphasis on chronic inflammation.

Key words

Sarcopenia obesity inflammation aging 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr 1997; 127 (Suppl 5): 990S–1S.PubMedGoogle Scholar
  2. 2.
    Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 2002; 50: 889–96.PubMedGoogle Scholar
  3. 3.
    Janssen I, Heymsfield SB, Wang ZM, Ross R. Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr. J Appl Physiol 2000; 89: 81–8.PubMedGoogle Scholar
  4. 4.
    Iannuzzi-Sucich M, Prestwood KM, Kenny AM. Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci 2002; 57: M772–7.PubMedGoogle Scholar
  5. 5.
    Murray MP, Duthie EH Jr, Gambert SR, Sepic SB, Mollinger LA. Age-related differences in knee muscle strength in normal women. J Gerontol 1985; 40: 275–80.PubMedGoogle Scholar
  6. 6.
    Murray MP, Gardner GM, Mollinger LA, Sepic SB. Strength of isometric and isokinetic contractions: knee muscles of men aged 20 to 86. Phys Ther 1980; 60: 412–9.PubMedGoogle Scholar
  7. 7.
    Baumgartner RN, Koehler KM, Gallagher D et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998; 147: 755–63.PubMedGoogle Scholar
  8. 8.
    Aniansson A, Sperling L, Rundgren A, Lehnberg E. Muscle function in 75-year-old men and women. A longitudinal study. Scand J Rehabil Med Suppl 1983; 9: 92–102.PubMedGoogle Scholar
  9. 9.
    Tinetti ME, Williams CS. Falls, injuries due to falls, and the risk of admission to a nursing home. N Engl J Med 1997; 337: 1279–84.PubMedGoogle Scholar
  10. 10.
    Wolfson L, Judge J, Whipple R, King M. Strength is a major factor in balance, gait, and the occurrence of falls. J Gerontol A Biol Sci Med Sci 1995; 50 (Spec No): 64–7.PubMedGoogle Scholar
  11. 11.
    Dorsey KB, Thornton JC, Heymsfield SB, Gallagher D. Greater lean tissue and skeletal muscle mass are associated with higher bone mineral content in children. Nutr Metab (Lond) 2010; 7: 41. PMCID: 2886077.Google Scholar
  12. 12.
    Clark BC, Manini TM. Functional consequences of sarcopenia and dynapenia in the elderly. Curr Opin Clin Nutr Metab Care 2010; 13: 271–6. PMCID: 2895460.PubMedCentralPubMedGoogle Scholar
  13. 13.
    Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R. The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc 2004; 52: 80–5.PubMedGoogle Scholar
  14. 14.
    Buford TW, Anton SD, Judge AR et al. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy. Ageing Res Rev 2010; 9: 369–83.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Greenlund LJ, Nair KS. Sarcopenia — consequences, mechanisms, and potential therapies. Mech Ageing Dev 2003; 124: 287–99.PubMedGoogle Scholar
  16. 16.
    Roubenoff R. The pathophysiology of wasting in the elderly. J Nutr 1999; 129 (1S Suppl): 256S–9S.PubMedGoogle Scholar
  17. 17.
    Glass D, Roubenoff R. Recent advances in the biology and therapy of muscle wasting. Ann NY Acad Sci 2010; 1211: 25–36.PubMedGoogle Scholar
  18. 18.
    Siu PM, Pistilli EE, Alway SE. Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading. J Appl Physiol 2008; 105: 1695–705. PMCID: 2612472.PubMedGoogle Scholar
  19. 19.
    Moylan JS, Reid MB. Oxidative stress, chronic disease, and muscle wasting. Muscle Nerve 2007; 35: 411–29.PubMedGoogle Scholar
  20. 20.
    Chung HY, Cesari M, Anton S et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 2009; 8: 18–30.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Buford TW, Cooke MB, Willoughby DS. Resistance exercise-induced changes of inflammatory gene expression within human skeletal muscle. Eur J Appl Physiol 2009; 107: 463–71.PubMedGoogle Scholar
  22. 22.
    Haddad F, Zaldivar F, Cooper DM, Adams GR. IL-6-induced skeletal muscle atrophy. J Appl Physiol 2005; 98: 911–7.PubMedGoogle Scholar
  23. 23.
    Schrager MA, Metter EJ, Simonsick E et al. Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol 2007; 102: 919–25. PMCID: 2645665.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Roubenoff R. Physical activity, inflammation, and muscle loss. Nutr Rev 2007; 65: S208–12.PubMedGoogle Scholar
  25. 25.
    Handel ML, McMorrow LB, Gravallese EM. Nuclear factor-kappa B in rheumatoid synovium. Localization of p50 and p65. Arthritis Rheum 1995; 38: 1762–70.PubMedGoogle Scholar
  26. 26.
    Meng SJ, Yu LJ. Oxidative stress, molecular inflammation and sarcopenia. Int J Mol Sci 2010; 11: 1509–26. PMCID: 2871128.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Chung HY, Lee EK, Choi YJ et al. Molecular Inflammation as an underlying mechanism of the aging process and age-related diseases. J Dent Res 2011; 90: 830–40. doi: 10.1177/0022034510387794. Epub 2011 Mar 29.PubMedGoogle Scholar
  28. 28.
    Mourkioti F, Rosenthal N. IGF-1, inflammation and stem cells: interactions during muscle regeneration. Trends Immunol 2005; 26: 535–42.PubMedGoogle Scholar
  29. 29.
    Toth MJ, Matthews DE, Tracy RP, Previs MJ. Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation. Am J Physiol Endocrinol Metab 2005; 288: E883–91.PubMedGoogle Scholar
  30. 30.
    Dirks AJ, Leeuwenburgh C. Tumor necrosis factor alpha signaling in skeletal muscle: effects of age and caloric restriction. J Nutr Biochem 2006; 17: 501–8.PubMedGoogle Scholar
  31. 31.
    Cesari M, Kritchevsky SB, Baumgartner RN et al. Sarcopenia, obesity, and inflammation — results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study. Am J Clin Nutr 2005; 82: 428–34.PubMedGoogle Scholar
  32. 32.
    Ferrante AW Jr. Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med 2007; 262: 408–14.PubMedGoogle Scholar
  33. 33.
    Thornell LE. Sarcopenic obesity: satellite cells in the aging muscle. Curr Opin Clin Nutr Metab Care 2011; 14: 22–7.PubMedGoogle Scholar
  34. 34.
    Carmeli E, Coleman R, Reznick AZ. The biochemistry of aging muscle. Exp Gerontol 2002; 37: 477–89.PubMedGoogle Scholar
  35. 35.
    Yu BP. Aging and oxidative stress: modulation by dietary restriction. Free Radic Biol Med 1996; 21: 651–68.PubMedGoogle Scholar
  36. 36.
    Kim DH, Kim CH, Kim MS et al. Suppression of age-related inflammatory NF-kappaB activation by cinnamaldehyde. Biogerontology 2007; 8: 545–54.PubMedGoogle Scholar
  37. 37.
    Kim HJ, Kim KW, Yu BP, Chung HY. The effect of age on cyclooxygenase-2 gene expression: NF-kappaB activation and IkappaBalpha degradation. Free Radic Biol Med 2000; 28: 683–92.PubMedGoogle Scholar
  38. 38.
    Kim HK, Park HR, Lee JS, Chung TS, Chung HY, Chung J. Down-regulation of iNOS and TNF-alpha expression by kaempferol via NF-kappaB inactivation in aged rat gingival tissues. Biogerontology 2007; 8: 399–408.PubMedGoogle Scholar
  39. 39.
    Chung HY, Sung B, Jung KJ, Zou Y, Yu BP. The molecular inflammatory process in aging. Antioxid Redox Signal 2006; 8: 572–81.PubMedGoogle Scholar
  40. 40.
    Franceschi C, Bonafe M, Valensin S et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann NY Acad Sci 2000; 908: 244–54.PubMedGoogle Scholar
  41. 41.
    Karin M. Role for IKK2 in muscle: waste not, want not. J Clin Invest 2006; 116: 2866–8. PMCID: 1626137.PubMedCentralPubMedGoogle Scholar
  42. 42.
    Zandi E, Chen Y, Karin M. Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate. Science 1998; 281: 1360–3.PubMedGoogle Scholar
  43. 43.
    Li YP, Chen Y, John J et al. TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. Faseb J 2005; 19: 362–70. PMCID: 3099533.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Li YP, Reid MB. NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes. Am J Physiol Regul Integr Comp Physiol 2000; 279: R1165–70.PubMedGoogle Scholar
  45. 45.
    Lee HC, Wei YH. Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol 2005; 37: 822–34.PubMedGoogle Scholar
  46. 46.
    Fisher GJ, Datta SC, Talwar HS et al. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 1996; 379: 335–9.PubMedGoogle Scholar
  47. 47.
    Messina S, Vita GL, Aguennouz M et al. Activation of NFkappaB pathway in Duchenne muscular dystrophy: relation to age. Acta Myol 2011; 30: 16–23.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Reid MB, Li YP. Tumor necrosis factor-alpha and muscle wasting: a cellular perspective. Respir Res 2001; 2: 269–72. PMCID: 59514.PubMedCentralPubMedGoogle Scholar
  49. 49.
    Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 2005; 37: 1974–84.PubMedGoogle Scholar
  50. 50.
    Jagoe RT, Lecker SH, Gomes M, Goldberg AL. Patterns of gene expression in atrophying skeletal muscles: response to food deprivation. Faseb J 2002; 16: 1697–712.PubMedGoogle Scholar
  51. 51.
    Hershko A. The ubiquitin system for protein degradation and some of its roles in the control of the cell-division cycle (Nobel lecture). Angew Chem Int Ed Engl 2005; 44: 5932–43.PubMedGoogle Scholar
  52. 52.
    Bodine SC, Latres E, Baumhueter S et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 2001; 294: 1704–8.PubMedGoogle Scholar
  53. 53.
    Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol 2003; 5: 87–90.PubMedGoogle Scholar
  54. 54.
    Li YP, Chen Y, Li AS, Reid MB. Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes. Am J Physiol Cell Physiol 2003; 285: C806–12.PubMedGoogle Scholar
  55. 55.
    Lecker SH. Ubiquitin-protein ligases in muscle wasting: multiple parallel pathways? Curr Opin Clin Nutr Metab Care 2003; 6: 271–5.PubMedGoogle Scholar
  56. 56.
    Lecker SH, Solomon V, Mitch WE, Goldberg AL. Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. J Nutr 1999; 129 (1S Suppl): 227S–37S.PubMedGoogle Scholar
  57. 57.
    Clavel S, Coldefy AS, Kurkdjian E, Salles J, Margaritis I, Derijard B. Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are upregulated in aged rat Tibialis Anterior muscle. Mech Ageing Dev 2006; 127: 794–801.PubMedGoogle Scholar
  58. 58.
    Sishi B, Loos B, Ellis B, Smith W, du Toit EF, Engelbrecht AM. Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model. Exp Physiol 2011; 96: 179–93.PubMedGoogle Scholar
  59. 59.
    Cai D, Frantz JD, Tawa NE Jr et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 2004; 119: 285–98.PubMedGoogle Scholar
  60. 60.
    Wyke SM, Tisdale MJ. NF-kappaB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitinproteasome system in skeletal muscle. Br J Cancer 2005; 92: 711–21. PMCID: 2361865.PubMedCentralPubMedGoogle Scholar
  61. 61.
    Reed SA, Senf SM, Cornwell EW, Kandarian SC, Judge AR. Inhibition of IkappaB kinase alpha (IKKalpha) or IKKbeta (IKKbeta) plus forkhead box O (Foxo) abolishes skeletal muscle atrophy. Biochem Biophys Res Commun 2011; 405: 491–6. PMCID: 3056397.PubMedCentralPubMedGoogle Scholar
  62. 62.
    Li YP, Schwartz RJ, Waddell ID, Holloway BR, Reid MB. Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor necrosis factor alpha. Faseb J 1998; 12: 871–80.PubMedGoogle Scholar
  63. 63.
    Raingeaud J, Gupta S, Rogers JS et al. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 1995; 270: 7420–6.PubMedGoogle Scholar
  64. 64.
    Murton AJ, Constantin D, Greenhaff PL. The involvement of the ubiquitin proteasome system in human skeletal muscle remodelling and atrophy. Biochim Biophys Acta 2008; 1782: 730–43.PubMedGoogle Scholar
  65. 65.
    Edstrom E, Altun M, Hagglund M, Ulfhake B. Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle. J Gerontol A Biol Sci Med Sci 2006; 61: 663–74.PubMedGoogle Scholar
  66. 66.
    Whitman SA, Wacker MJ, Richmond SR, Godard MP. Contributions of the ubiquitin-proteasome pathway and apoptosis to human skeletal muscle wasting with age. Pflugers Arch 2005; 450: 437–46.PubMedGoogle Scholar
  67. 67.
    Hawke TJ, Garry DJ. Myogenic satellite cells: physiology to molecular biology. J Appl Physiol 2001; 91: 534–51.PubMedGoogle Scholar
  68. 68.
    Snijders T, Verdijk LB, van Loon LJ. The impact of sarcopenia and exercise training on skeletal muscle satellite cells. Ageing Res Rev 2009; 8: 328–38.PubMedGoogle Scholar
  69. 69.
    Hawke TJ. Muscle stem cells and exercise training. Exerc Sport Sci Rev 2005; 33: 63–8.PubMedGoogle Scholar
  70. 70.
    Petrella JK, Kim JS, Cross JM, Kosek DJ, Bamman MM. Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women. Am J Physiol Endocrinol Metab 2006; 291: E937–46.PubMedGoogle Scholar
  71. 71.
    Kadi F, Charifi N, Denis C, Lexell J. Satellite cells and myonuclei in young and elderly women and men. Muscle Nerve 2004; 29: 120–7.PubMedGoogle Scholar
  72. 72.
    Verdijk LB, Koopman R, Schaart G, Meijer K, Savelberg HH, van Loon LJ. Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly. Am J Physiol Endocrinol Metab 2007; 292: E151–7.PubMedGoogle Scholar
  73. 73.
    Morse CI, Thom JM, Reeves ND, Birch KM, Narici MV. In vivo physiological cross-sectional area and specific force are reduced in the gastrocnemius of elderly men. J Appl Physiol 2005; 99: 1050–5.PubMedGoogle Scholar
  74. 74.
    Morse CI, Thom JM, Mian OS, Birch KM, Narici MV. Gastrocnemius specific force is increased in elderly males following a 12-month physical training programme. Eur J Appl Physiol 2007; 100: 563–70.PubMedGoogle Scholar
  75. 75.
    Verdijk LB, Gleeson BG, Jonkers RA et al. Skeletal muscle hypertrophy following resistance training is accompanied by a fiber type-specific increase in satellite cell content in elderly men. J Gerontol A Biol Sci Med Sci 2009; 64: 332–9. PMCID: 2655000.PubMedGoogle Scholar
  76. 76.
    Kim JS, Kosek DJ, Petrella JK, Cross JM, Bamman MM. Resting and load-induced levels of myogenic gene transcripts differ between older adults with demonstrable sarcopenia and young men and women. J Appl Physiol 2005; 99: 2149–58.PubMedGoogle Scholar
  77. 77.
    Degens H. Age-related skeletal muscle dysfunction: causes and mechanisms. J Musculoskelet Neuronal Interact 2007; 7: 246–52.PubMedGoogle Scholar
  78. 78.
    Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 2005; 433: 760–4.PubMedGoogle Scholar
  79. 79.
    Rader EP, Faulkner JA. Recovery from contraction-induced injury is impaired in weight-bearing muscles of old male mice. J Appl Physiol 2006; 100: 656–61.PubMedGoogle Scholar
  80. 80.
    Rader EP, Faulkner JA. Effect of aging on the recovery following contraction-induced injury in muscles of female mice. J Appl Physiol 2006; 101: 887–92.PubMedGoogle Scholar
  81. 81.
    Carlson BM, Faulkner JA. Muscle transplantation between young and old rats: age of host determines recovery. Am J Physiol 1989; 256: C1262–6.PubMedGoogle Scholar
  82. 82.
    Degens H. The role of systemic inflammation in age-related muscle weakness and wasting. Scand J Med Sci Sports 2010; 20: 28–38.PubMedGoogle Scholar
  83. 83.
    Langen RC, Schols AM, Kelders MC, van der Velden JL, Wouters EF, Janssen-Heininger YM. Muscle wasting and impaired muscle regeneration in a murine model of chronic pulmonary inflammation. Am J Respir Cell Mol Biol 2006; 35: 689–96.PubMedGoogle Scholar
  84. 84.
    Langen RC, Van Der Velden JL, Schols AM, Kelders MC, Wouters EF, Janssen-Heininger YM. Tumor necrosis factor-alpha inhibits myogenic differentiation through MyoD protein destabilization. Faseb J 2004; 18: 227–37.PubMedGoogle Scholar
  85. 85.
    Chen SE, Jin B, Li YP. TNF-alpha regulates myogenesis and muscle regeneration by activating p38 MAPK. Am J Physiol Cell Physiol 2007; 292: C1660–71. PMCID: 3099536.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Langen RC, Schols AM, Kelders MC, Van Der Velden JL, Wouters EF, Janssen-Heininger YM. Tumor necrosis factor-alpha inhibits myogenesis through redox-dependent and —independent pathways. Am J Physiol Cell Physiol 2002; 283: C714–21.PubMedGoogle Scholar
  87. 87.
    Guttridge DC, Mayo MW, Madrid LV, Wang CY, Baldwin AS Jr. NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 2000; 289: 2363–6.PubMedGoogle Scholar
  88. 88.
    Langen RC, Schols AM, Kelders MC, Wouters EF, Janssen-Heininger YM. Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-kappaB. Faseb J 2001; 15: 1169–80.PubMedGoogle Scholar
  89. 89.
    Sabourin LA, Rudnicki MA. The molecular regulation of myogenesis. Clin Genet 2000; 57: 16–25.PubMedGoogle Scholar
  90. 90.
    Dirks AJ, Leeuwenburgh C. The role of apoptosis in age-related skeletal muscle atrophy. Sports Med 2005; 35: 473–83.PubMedGoogle Scholar
  91. 91.
    McArdle A, Maglara A, Appleton P, Watson AJ, Grierson I, Jackson MJ. Apoptosis in multinucleated skeletal muscle myotubes. Lab Invest 1999; 79: 1069–76.PubMedGoogle Scholar
  92. 92.
    Alway SE, Siu PM. Nuclear apoptosis contributes to sarcopenia. Exerc Sport Sci Rev 2008; 36: 51–7. PMCID: 2778230.PubMedCentralPubMedGoogle Scholar
  93. 93.
    Dirks AJ, Leeuwenburgh C. Aging and lifelong calorie restriction result in adaptations of skeletal muscle apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis, caspase-3, and caspase-12. Free Radic Biol Med 2004; 36: 27–39.PubMedGoogle Scholar
  94. 94.
    Alway SE, Degens H, Krishnamurthy G, Smith CA. Potential role for Id myogenic repressors in apoptosis and attenuation of hypertrophy in muscles of aged rats. Am J Physiol Cell Physiol 2002; 283: C66–76.PubMedGoogle Scholar
  95. 95.
    Pistilli EE, Jackson JR, Alway SE. Death receptor-associated pro-apoptotic signaling in aged skeletal muscle. Apoptosis 2006; 11: 2115–26.PubMedGoogle Scholar
  96. 96.
    Phillips T, Leeuwenburgh C. Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. Faseb J 2005; 19: 668–70.PubMedGoogle Scholar
  97. 97.
    Chabi B, Ljubicic V, Menzies KJ, Huang JH, Saleem A, Hood DA. Mitochondrial function and apoptotic susceptibility in aging skeletal muscle. Aging Cell 2008; 7: 2–12.PubMedGoogle Scholar
  98. 98.
    Cadenas E. Mitochondrial free radical production and cell signaling. Mol Aspects Med 2004; 25: 17–26.PubMedGoogle Scholar
  99. 99.
    Nitahara JA, Cheng W, Liu Y et al. Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. J Mol Cell Cardiol 1998; 30: 519–35.PubMedGoogle Scholar
  100. 100.
    Squier TC, Bigelow DJ. Protein oxidation and age-dependent alterations in calcium homeostasis. Front Biosci 2000; 5: D504–26.PubMedGoogle Scholar
  101. 101.
    Siu PM, Pistilli EE, Butler DC, Alway SE. Aging influences cellular and molecular responses of apoptosis to skeletal muscle unloading. Am J Physiol Cell Physiol 2005; 288: C338–49.PubMedGoogle Scholar
  102. 102.
    Marzetti E, Wohlgemuth SE, Lees HA, Chung HY, Giovannini S, Leeuwenburgh C. Age-related activation of mitochondrial caspaseindependent apoptotic signaling in rat gastrocnemius muscle. Mech Ageing Dev 2008; 129: 542–9. PMCID: 2585824.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM. Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem 1999; 274: 5053–60.PubMedGoogle Scholar
  104. 104.
    Baumgartner RN. Body composition in healthy aging. Ann NY Acad Sci 2000; 904: 437–48.PubMedGoogle Scholar
  105. 105.
    Roubenoff R. Sarcopenic obesity: the confluence of two epidemics. Obes Res 2004; 12: 887–8.PubMedGoogle Scholar
  106. 106.
    Zamboni M, Mazzali G, Fantin F, Rossi A, Di Francesco V. Sarcopenic obesity: a new category of obesity in the elderly. Nutr Metab Cardiovasc Dis 2008; 18: 388–95.PubMedGoogle Scholar
  107. 107.
    Song MY, Ruts E, Kim J, Janumala I, Heymsfield S, Gallagher D. Sarcopenia and increased adipose tissue infiltration of muscle in elderly African American women. Am J Clin Nutr 2004; 79: 874–80.PubMedGoogle Scholar
  108. 108.
    Cree MG, Newcomer BR, Katsanos CS et al. Intramuscular and liver triglycerides are increased in the elderly. J Clin Endocrinol Metab 2004; 89: 3864–71.PubMedGoogle Scholar
  109. 109.
    Cesari M, Kritchevsky SB, Baumgartner RN et al. Sarcopenia, obesity, and inflammation — results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study. Am J Clin Nutr 2005; 82: 428–34.PubMedGoogle Scholar
  110. 110.
    Jensen GL. Inflammation: roles in aging and sarcopenia. JPEN J Parenter Enteral Nutr 2008; 32: 656–9.PubMedGoogle Scholar
  111. 111.
    Yende S, Waterer GW, Tolley EA et al. Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax 2006; 61: 10–6.PubMedGoogle Scholar
  112. 112.
    Mundy GR. Osteoporosis and inflammation. Nutr Rev 2007; 65: 147–51.Google Scholar
  113. 113.
    Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science (New York) 1993; 259: 87–91.Google Scholar
  114. 114.
    Marzetti E, Leeuwenburgh C. Skeletal muscle apoptosis, sarcopenia and frailty at old age. Exp Gerontol 2006; 41: 1234–8.PubMedGoogle Scholar
  115. 115.
    Roubenoff R. Sarcopenic obesity: the confluence of two epidemics. Obes Res 2004; 12: 887–8.PubMedGoogle Scholar
  116. 116.
    Peterson MD, Liu D, Gordish-Dressman H et al. Adiposity attenuates muscle quality and the adaptive response to resistance exercise in non-obese, healthy adults. Int J Obes (Lond) 2011; 35: 1095–103. doi: 10.1038/ijo.2010.257. Epub 2010 Dec 7.Google Scholar
  117. 117.
    Awad AB, Bradford PG. Adipose tissue and inflammation. Boca Raton, FL: Taylor & Francis, 2010.Google Scholar
  118. 118.
    Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 2007; 56: 1010–3.PubMedGoogle Scholar
  119. 119.
    Neels JG, Olefsky JM. Inflamed fat: what starts the fire? J Clin Invest 2006; 116: 33–5. PMCID: 1323268.PubMedCentralPubMedGoogle Scholar
  120. 120.
    Zamboni M, Mazzali G, Zoico E et al. Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes (Lond) 2005; 29: 1011–29.Google Scholar
  121. 121.
    Coll T, Barroso E, Alvarez-Guardia D et al. The role of peroxisome proliferator-activated receptor beta/delta on the inflammatory basis of metabolic disease. PPAR Res 2010; 2010. PMCID: 2913795.Google Scholar
  122. 122.
    Coll T, Alvarez-Guardia D, Barroso E et al. Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor-{kappa}B activation and insulin resistance in skeletal muscle cells. Endocrinology 2010; 151: 1560–9.PubMedGoogle Scholar
  123. 123.
    Perseghin G, Petersen K, Shulman GI. Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord 2003; 27 (Suppl 3): S6–11.Google Scholar
  124. 124.
    Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 1996; 27: 665–8.Google Scholar

Copyright information

© Springer Internal Publishing Switzerland 2012

Authors and Affiliations

  • Edward Jo
    • 1
  • Sang-Rok Lee
    • 1
  • Bong-Sup Park
    • 1
  • Jeong-Su Kim
    • 1
    Email author
  1. 1.Department of Food, Nutrition, and Exercise SciencesThe Florida State UniversityTallahasseeUSA

Personalised recommendations