Sarcopenia and cachexia: The adaptations of negative regulators of skeletal muscle mass

Journal of Cachexia, Sarcopenia and Muscle

Volumn 3, Issue 2, 2012, Pages 77-94

  Sakuma, Kunihiro ^a   Yamaguchi, Akihiko ^b  

^a TOYOHASHI UNIVERSITY OF TECHNOLOGY   (Japan)

^b HEALTH SCIENCES UNIVERSITY OF HOKKAIDO   (Japan)

Author keywords

Atrogin 1; Cachexia; Myostatin; NF B; Sarcopenia; Skeletal muscle

Indexed keywords

ACTIVIN RECEPTOR LIKE KINASE 1; ATROGIN 1; BECLIN 1; CALCINEURIN; CALCIUM ION; CALPAIN; CANNABINOID; CORTICOSTEROID; GAMMA INTERFERON; GROWTH HORMONE; IBUPROFEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; INTERLEUKIN 6; MAMMALIAN TARGET OF RAPAMYCIN; MYOSTATIN; NOTEXIN; PF 354; PROTEIN INHIBITOR; PROTEIN KINASE C; REACTIVE OXYGEN METABOLITE; SMAD3 PROTEIN; SOMATOMEDIN BINDING PROTEIN 1; TESTOSTERONE; TRANSCRIPTION FACTOR FOXO; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AGING; APOPTOSIS; AUTOPHAGY; CACHEXIA; CALCIUM CELL LEVEL; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; CHRONIC OBSTRUCTIVE LUNG DISEASE; CYTOPLASM; DIET SUPPLEMENTATION; DISEASE COURSE; DNA FRAGMENTATION; DOWN REGULATION; ENDOPLASMIC RETICULUM; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; FATIGUE; HAND GRIP; HAND STRENGTH; HEALTH CARE COST; HEART FAILURE; HEART LEFT VENTRICLE FAILURE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; LEAN BODY WEIGHT; LIGHT CHAIN; LOW DRUG DOSE; LUNG PARENCHYMA; MUSCLE ATROPHY; MUSCLE MASS; MUSCLE REGENERATION; NONHUMAN; OFF LABEL DRUG USE; OXIDATIVE STRESS; PHYSICAL ACTIVITY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; PUBLIC HEALTH PROBLEM; RESISTANCE TRAINING; REVIEW; SARCOPLASM; SKELETAL MUSCLE; UBIQUITINATION; WEIGHT GAIN; WEIGHT REDUCTION;

EID: 84866549876     PISSN: 21905991     EISSN: 21906009     Source Type: Journal    
DOI: 10.1007/s13539-011-0052-4     Document Type: Review

References (250)

1. Rosenberg I. Summary comments. Am J Clin Nutr. 1989;50:1231-3.
2. Roubenoff R, Heymsfield SB, Kehayias JJ, Cannon JG, Rosenberg IH. Standardization of nomenclature of body composition in weight loss. Am J Clin Nutr. 1997;66:192-6.
3. Roubenoff R, Kehayias J. The meaning and measurement of lean body mass. Nutr Rev. 1991;46:163-75.
4. Keys A, Brozek J, Henschel A, Mickelsen O, Taylor HL. The biology of human starvation. Minneapolis: University of Minnesota Press; 1950.
5. Hughes V, Roubenoff R. Sarcopenia: current concepts. J Gerontol Med Sci. 2000;55A:M716-24.
6. Lenk K, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle. 2010;1:9-21.
7. Candow DG, Chilibeck PD. Differences in size, strength, and power of upper and lower body muscle groups in young and older men. J Gerontol A Biol Sci Med Sci. 2005;60:148-56.
8. Melton 3rd LJ, Khosla S, Crowson CS, O'Fallon WM, Riggs BL. Epidemiology of sarcopenia. J Am Geriat Soc. 2000;48:625-30.
9. von Haehling S, Morley JE, Anker SD. An overview of sarcopenia: facts and numbers on prevalence and clinical impact. J Cachexia Sarcopenia Muscle. 2010;1:129-33.
10. Baumgartner RN, Waters DL, Gallagher D, Morley JE, Garry PJ. Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev. 1999;107:123-36.
11. 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.
12. Short KR, Nair KS. The effect of age on protein metabolism. Curr Opin Clin Nutr Metab Care. 2000;3:39-44.
13. Short KR, Vittone JL, Bigelow JL, Proctor DN, Nair KS. Age and aerobic exercise training effects on whole body and muscle protein metabolism. Am J Physiol Endocrinol Metab. 2004;286: E92-E101.
14. Lexell J. Human aging, muscle mass, and fiber type composition. J Gerontol A Biol Sci Med Sci. 1995;50:11-6.
15. Larsson L. Morphological and functional characteristics of the ageing skeletal muscle in man. A cross-sectional study. Acta Physiol Scand Suppl. 1978;457:1-36.
16. 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.
17. Verdijk LB, Gleeson BG, Jonkers RAM, Meijer K, Savelberg HHCM, Dendale P, 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.
18. Brack AS, Bildsoe H, Hughes SM. Evidence that satellite cell decrement contributes to preferential decline in nuclear number from large fibres during murine age-related muscle atrophy. J Cell Sci. 2005;118:4813-21.
19. Collins CA, Zammit PS, Ruiz AP, Morgan JE, Partridge TA. A population of myogenic stem cells that survives skeletal muscle aging. Stem Cells. 2007;25:885-94.
20. Day K, Shefer G, Shearer A, Yablonka-Reuveni Z. The depletion of skeletal muscle satellite cells with age is concomitant with reduced capacity of single progenitors to produce reserve progeny. Dev Biol. 2010;340:330-43.
21. Conboy IM, Conboy MJ, Smythe GM, Rando TA. Notchmediated restoration of regenerative potential to aged muscle. Science. 2003;302:1575-7.
22. Wagners AJ, Conboy IM. Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell. 2005;122:659-67.
23. Lexell J. Ageing and human muscle: observations from Sweden. Can J Appl Physiol. 1993;18:2-18.
24. Roubenoff R, Hughes VA. Sarcopenia: current concepts. J Gerontol A Biol Sci Med Sci. 2000;55:M716-24.
25. Scott D, Blizzard L, Fell J, Jones G. The epidemiology of sarcopenia in community living older adults: what role does lifestyle play? J Cachexia Sarcopenia Muscle. 2010;2:125-34.
26. Sakuma K, Akiho M, Nakashima H, Akima H, Yasuhara M. Agerelated reductions in expression of serum response factor and myocardin-related transcription factor A in mouse skeletal muscles. Biochim Biophys Acta Mol Basis Dis. 2008;1782:453-61.
27. Sakuma K, Yamaguchi A. Molecular mechanisms in aging and current strategies to counteract sarcopenia. Curr Aging Sci. 2010;3:90-101.
28. Sakuma K, Yamaguchi A (2011) Sarcopenia: molecular mechanisms and current therapeutic strategy. In: Perloft JW, Wong AH (eds) Cell aging. Nova Science, New York (in press)
29. Thomson DM, Gordon SE. Impaired overload-induced muscle growth is associated with diminished translational signaling in aged rat fast-twitch skeletal muscle. J Physiol. 2006;574:291-305.
30. Dahele M, Fearon KC. Research methodology: cancer cachexia syndrome. Palliat Med. 2004;84:209-38.
31. Anker SD, Sharma R. The syndrome of cardiac cachexia. Int J Cardiol. 2002;85:51-66.
32. Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev. 2009;89:381-410.
33. Deans C, Wigmore SJ. Systemic inflammation, cachexia and prognosis in patients with cancer. Curr Opin Clin Nurs Metal Care. 2005;8:265-9.
34. Mitch WE, Price SR. Transcription factors and muscle cachexia: is there a therapeutic target? Lancet. 2001;357:734-5.
35. Kumar NB, Kazi A, Smith T, Crocker T, Yu D, Reich RR, et al. Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment. Curr Treat Options Oncol. 2010;11:107-17.
36. Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet. 1997;349:1050-3.
37. Pu CT, Johnson MT, Forman DE, Hausdorff JM, Roubenoff R, Foldvari M, et al. Randomized trial of progressive resistance training to counteract the myopathy of chronic heart failure. J Appl Physiol. 2001;90:2341-50.
38. MacDougall JD, Green HJ, Sutton JR, Coates G, Cymerman A, Yung P, et al. Operation Everest II: structural adaptations in skeletal muscle in response to extreme stimulated altitude. Acta Physiol Scand. 1991;142:421-7.
39. Wouters EF. Management of severe COPD. Lancet. 2004;364:883-95.
40. Wouters EF. Local and systemic inflammation in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2:26-33.
41. Kadowaki M, Kanazawa T. Amino acids as regulators of proteolysis. J Nutr. 2003;133:2052S-6S.
42. Grumati P, Coletto L, Sabatelli P, Cescon M, Angelin A, Bertaggia E, et al. Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nat Med. 2010;16:1313-20.
43. Marino G, Uria JA, Puente XS, Quesada V, Bordallo J, Lopez-Otin C. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. J Biol Chem. 2003;278:3671-8.
44. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007;6:458-71.
45. Ogata T, Oishi Y, Higuchi M, Muraoka I. Fasting-related autophagic response in slow-and fast-twitch skeletal muscles. Biochem Biophys Res Commun. 2010;394:136-40.
46. O'Leary MFN, Hood DA. Denervation-induced oxidative stress and autophagy signaling in muscle. Autophagy. 2009;5:230-1.
47. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001;294:1704-8.
48. 2+-dependent proteolysis in muscle wasting. Int J Biochem Cell Biol. 2005;37:2134-46.
49. Smith IJ, Dodd SL. Calpain activation causes a proteasomedependent increase in protein degradation and inhibits the Akt signaling pathway in rat diaphragm muscle. Exp Physiol. 2007;92:561-73.
50. Du J, Wang X, Miereles C, Bailey JL, Debigare R, Zheng B. Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest. 2004;113:115-23.
51. Moresi V, Presterá A, Scicchitano BM, Molinaro M, Teodori L, Sassoon D, et al. Tumor necrosis factor-alpha inhibition of skeletal muscle regeneration is mediated by a caspase-dependent stem cell response. Stem Cells. 2008;26:997-1008.
52. Hershko A, Ciechanover A. Mechanisms of intracellular protein breakdown. Annu Rev Biochem. 1982;51:335-64.
53. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82:373-428.
54. Attaix D, Aurousseau E, Combaret L, Kee A, Larbaud D, Ralliére C, et al. Ubiquitin-proteasome-dependent proteolysis in skeletal muscle. Reprod Nutr Dev. 1998;38:153-65.
55. Tisdale MJ. The ubiquitin-proteasome pathway as a therapeutic target for muscle wasting. J Support Oncol. 2005;3:209-17.
56. Kwak KS, Zhou X, Solomon V, Baracos VE, Davis J, Bannon AW, et al. Regulation of protein catabolism by muscle-specific and cytokine-inducible ubiquitin ligase E3alpha-II during cancer cachexia. Cancer Res. 2004;64:8193-8.
57. Cai D, Frantz JD, Tawa Jr NE, Melendez PA, Oh BC, Lidov HG, et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell. 2004;119:285-9.
58. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004;117:399-412.
59. Deshaies RJ. SCF and Cullin/Ring H2-based ubiquitin ligases. Annu Rev Cell Dev Biol. 1999;15:435-67.
60. Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem. 1996;65:801-47.
61. Rivett A. Proteasomes: multicatalytic proteinase complexes. Biochem J. 1993;291:1-10.
62. Baumeister W, Walz J, Zühl F, Seemüller E. The proteasome: paradigm of a self-compartmentalizing protease. Cell. 1998;92:367-80.
63. Glass DJ. Signaling pathways perturbing muscle mass. Curr Opin Clin Nutr Metabol Care. 2010;13:225-9.
64. Latres E, Amini AR, Amini AA, Griffiths J, Martin FJ, Wei Y, et al. Insulin-like growth factor-1 (IGF-1) inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/ mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem. 2005;280:2737-44.
65. Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 2004;18:39-51.
66. Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, et al. The IGF-I/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell. 2004;14:395-403.
67. Bossola M, Pacelli F, Costelli P, Tortorelli A, Rosa F, Doglietto GB. Proteasome activities in the rectus abdominis muscle of young and older individuals. Biogerontology. 2008;9:261-8.
68. Cai D, Lee KK, Li M, Tang MK, Chan KM. Ubiquitin expression is up-regulated in human and rat skeletal muscles during aging. Arch Biochem Biophys. 2004;425:42-50.
69. Pattison JS, Folk LC, Madsen RW, Childs TE, Booth FW. Transcriptional profiling identifies extensive downregulation of extracellular matrix gene expression in sarcopenic rat soleus muscle. Physiol Genomics. 2003;15:34-43.
70. Combaret L, Dardevet D, Béchet D, Taillandier D, Mosoni L, Attaix D. Skeletal muscle proteolysis in aging. Curr Opin Clin Nutr Metab Care. 2009;12:37-41.
71. DeRuisseau KC, Kavazis AN, Powers SK. Selective downregulation of ubiquitin conjugation cascade mRNA occurs in the senescent rat soleus muscle. Exp Gerontol. 2005;40:526-31.
72. Altun M, Besche HC, Overkleeft HS, Piccirillo R, Edelmann MJ, Kessler BM, et al. Muscle wasting in aged, sarcopenic rats is associated with enhanced activity of the ubiquitin proteasome pathway. J Biol Chem. 2010;285:39597-608.
73. Welle S, Brooks AL, Delehany JM, Needler N, Thornton CA. Gene expression profile of aging in human muscle. Physiol Genomics. 2003;14:149-59.
74. 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.
75. Clavel S, Coldefy AS, Kurkdjian E, Salles J, Margaritis I, Derijard B. Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat tibialis anterior muscle. Mech Ageing Dev. 2006;127:794-801.
76. Edström E, Altun M, Hägglund M, Ulfhake B. Atrogin-1/MAFbx and MuRF1 are downregulated in ageing-related loss of skeletal muscle. J Gerontol A Biol Sci Med Sci. 2006;61:663-74.
77. Léger B, Derave W, De Bock K, Hespel P, Russell AP. Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. Rejuvenation Res. 2008;11:163-75.
78. Sacheck JM, Hyatt JP, Raffaello A, Jagoe RT, Roy RR, Edgerton VR, et al. Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J. 2007;21:140-55.
79. Attaix D, Mosoni L, Dardevet D, Combaret L, Mirand PP, Grizard J. Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods. Int J Biochem Cell Biol. 2005;37:1962-73.
80. Husom AD, Peters EA, Kolling EA, Fugere NA, Thompson LV, Ferrington DA. Altered proteasome function and subunit composition in aged muscle. Arch Biochem Biophys. 2004;421:67-76.
81. Sakuma K, Yamaguchi A. Inhibitors of myostatin-and proteasome-dependent signaling for attenuating muscle wasting. Recent Pat Regen Med. 2011;1:284-98.
82. Khal J, Hine AV, Fearon KCH, Dejong CHC, Tisdale MJ. Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. Int J Biochem Cell Biol. 2005;37:2196-206.
83. Filippatos GS, Anker SD, Kremastinos DT. Pathophysiology of peripheral muscle wasting in cardiac cachexia. Curr Opin Clin Nutr Metab Care. 2005;8:249-54.
84. Temparis S, Asensi M, Taillandier D, Aurousseau E, Larbaud D, Obled A, et al. Increased ATP-ubiquitin-dependent proteolysis in skeletal muscle of tumor-bearing rats. Cancer Res. 1994;54:5568-73.
85. Khal J, Wyke SM, Russell ST, Hine AV, Tisdale MJ. Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia. Br J Cancer. 2005;93:774-80.
86. Llovera M, Carbó N, García-Martínez C, Costelli P, Tessitore L, Baccino FM, et al. Anti-TNF treatment reverts increased muscle ubiquitin gene expression in tumor-bearing rats. Biochem Biophys Res Commun. 1996;221:653-5.
87. Costelli P, Muscaritoli M, Bossola M, Penna F, Reffo P, Bonetto A, et al. IGF-I is downregulated in experimental cancer cachexia. Am J Physiol Regul Integr Comp Physiol. 2006;291:R674-83.
88. Paul PK, Gupta SK, Bhatnagar S, Panguluri SK, Darnay BG, Choi Y, et al. Targeting ablation of TRAF6 inhibits skeletal muscle wasting in mice. J Cell Biol. 2010;191:1395-411.
89. Murton AJ, Constantin D, Greenhalf PL. The involvement of the ubiquitin proteasome system in human skeletal muscle remodeling and atrophy. Biochim Biophys Acta Mol Basis Dis. 2008;1782:730-43.
90. Baracos VE, DeVivo C, Hoyle DH, Goldberg AL. Activation of the ATP-ubiquitin-proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma. Am J Physiol Endocrinol Metab. 1995;268:E996-E1006.
91. Chai J, Wu Y, Sheng ZZ. Role of ubiquitin-proteasome pathway in skeletal muscle wasting in rats with endotoxemia. Crit Care Med. 2003;31:1802-7.
92. Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004;6:463-77.
93. Meijer AJ, Codogno P. Regulation and role of autophagy in mammalian cell. Int J Biochem Cell Biol. 2004;36:2445-62.
94. Xie Z, Klionsky DJ. Autophagosome formation: core machinery and adaptations. Nat Cell Biol. 2007;9:1102-9.
95. Sandri M. Autophagy in health and disease. 3. Involvement of autophagy in muscle atrophy. Am J Physiol Cell Physiol. 2010;298: C1291-7.
96. Lee HK, Marzella L. Regulation of intracellular protein degradation with special reference to lysosomes: role in cell physiology and pathology. Int Rev Exp Pathol. 1994;35:39-147.
97. Cuervo AM. Autophagy: many paths to the same end. Mol Cell Biochem. 2004;263:55-72.
98. Raben N, Schreiner C, Baum R, Takikita S, Xu S, Xie T, et al. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder-murine Pompe disease. Autophagy. 2010;6:1078-89.
99. Wang CW, Klionsky DJ. The molecular mechanism of autophagy. Mol Med. 2003;9:65-76.
100. Noglaska A, Terracciano C, D'Agostino C, Engel WK, Askanas V. p62/SQSTM1 is overexpressed and prominently accumulated in inclusion of sporadic inclusion-body myositis muscle fibers, and can help differentiating it from polymyositis and dermatomyositis. Acta Neuropath. 2009;118:407-13.
101. Bjorkoy G, Lamak T, Brech A, Outzen H, Perander M, Overvatn A, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005;171:603-14.
102. Pankiv S, Clausen TH, Lamak T, Brech A, Bruun JA, Outzen H, et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007;282:24131-45.
103. Zhao J, Brault JJ, Schild A, Cao P, Sandri M, Schiaffino S, et al. FoxO3 coordinately activates protein degradation by the autophagic/ lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 2007;6:472-83.
104. Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, et al. Autophagy is required to maintain muscle mass. Cell Metab. 2009;10:507-15.
105. Cuervo AM, Bergamini E, Brunk UT, Droge W, Ffrench M, Terman A. Autophagy and aging: the importance of maintaining "clean" cells. Autophagy. 2005;1:131-40.
106. Terman A, Brunk UT. Oxidative stress, accumulation of biological 'garbage', and aging. Antioxid Redox Signal. 2006;8:197-204.
107. Donati A, Cavallini G, Paradiso C, Vittorini S, Pollera M, Gori Z, et al. Age-related changes in the regulation of autophagic proteolysis in rat isolated hepatocytes. J Gerontol A Biol Sci Med Sci. 2001;56:B288-93.
108. Wohlgemuth SE, Julian D, Akin DE, Fried J, Toscano K, Leeuwenburgh C, et al. Autophagy in the heart and liver during normal aging and calorie restriction. Rejuvenation Res. 2007;10:281-92.
109. Gaugler M, Brown A, Merrell E, Disanto-Rose M, Rathmacher JA, Reynolds 4th TH. PKB signaling and atrogene expression in skeletal muscle of aged mice. J Appl Physiol. 2011;111:192-9.
110. McMullen CA, Ferry AL, Gamboa JL, Andrade FH, Dupont-Versteegden EE. Age-related changes of cell death pathways in rat extraocular muscle. Exp Gerontol. 2009;44:420-5.
111. Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT. Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci USA. 2009;106:20405-10.
112. Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol. 2010;45:138-48.
113. Kihara A, Noda T, Ishihara N, Ohsumi Y. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol. 2001;152:519-30.
114. Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol. 2005;169:425-34.
115. Ryter SW, Chen Z-H, Kim HP, Choi AMK. Autophagy in chronic obstructive pulmonary disease. Autophagy. 2009;5:235-7.
116. Plant PJ, Brooks D, Faughnan M, Bayley T, Bain J, Singer L, et al. Cellular markers of muscle atrophy in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2010;42:461-71.
117. Lee SJ. Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol. 2004;20:61-86.
118. Langley B, Thomas M, Bishop A, Sharma M, Gilmour S, Kambadur R. Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem. 2002;277:49831-40.
119. Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J, et al. Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast differentiation. J Biol Chem. 2000;275:40235-43.
120. YangW, Zhang Y, Li Y, Wu Z, Zhu D. Myostatin induces cyclin D1 degradation to cause cell cycle arrest through a phosphatidylinositol 3-kinase/AKT/GSK-3β pathway and is antagonized by insulin-like growth factor 1. J Biol Chem. 2007;282:3799-808.
121. Lee SJ, McPherron AM. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA. 2001;98:9306-11.
122. Allen DL, Unterman TG. Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors. Am J Physiol Cell Physiol. 2007;292:C188-99.
123. Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol. 2009;296:C1258-70.
124. Sartori R, Milan G, Patron M, Mammucari C, Blaauw B, Abraham R, et al. Smad2 and 3 transcription factors control muscle mass in adulthood. Am J Physiol Cell Physiol. 2009;296: C1248-57.
125. Bradley L, Yaworsky PJ, Walsh FS. Myostatin as a therapeutic target for musculoskeletal disease. Cell Mol Life Sci. 2008;65:2119-24.
126. Bogdanovich S, Krag TO, Barton ER, Morris LD, Whittemore LA, Ahima RS, et al. Functional improvement of dystrophic muscle by myostatin blockade. Nature. 2002;420:418-21.
127. Holzbaur EL, Howland DS, Weber N, Wallace K, She Y, Kwak S, et al. Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis. Neurobiol Dis. 2006;23:697-707.
128. Wagner KR, Fleckenstein JL, Amato AA, Barohn RJ, Bushby K, Escolar DM, et al. A phase I/II trial of MYO-029 in adult subjects with muscular dystrophy. Ann Neurol. 2008;63:561-71.
129. Sakuma K, Watanabe K, Sano M, Uramoto I, Totsuka T. Differential adaptation of growth and differentiation factor 8/ myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating, and denervated rat muscles. Biochim Biophys Acta, Mol Cell Res. 2000;1497:77-88.
130. Sakuma K, Watanabe K, Hotta N, Koike T, Ishida K, Katayama K, et al. The atrophy of skeletal muscle after lower limb unloading in humans. Acta Physiol (Oxf). 2009;197:151-9.
131. Wehling M, Cai B, Tidball JG. Modulation of myostatin expression duringmodified muscle use. FASEB J. 2000;14:103-10.
132. Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, et al. Organization of the human myostatin gene and expression in health men and HIV-infected men with muscle wasting. Proc Natl Acad Sci USA. 1998;95:14938-43.
133. Carlson ME, Hsu M, Conboy IM. Imbalance between pSmad3 and Notch induces CDK inhibitors is old muscle stem cells. Nature. 2008;454:528-32.
134. Haddad F, Adams GR. Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophy. J Appl Physiol. 2006;100:1188-203.
135. Siriett V, Platt L, Salerno MS, Ling N, Kambadur R, Sharma M. Prolonged absence of myostatin reduces sarcopenia. J Cell Physiol. 2006;209:866-73.
136. Lebrasseur NK, Schelhorn TM, Bernardo BL, Cosgrove PG, Loria PM, Brown TA. Myostatin inhibition enhances the effects on performance and metabolic outcomes in aged mice. J Gerontol A Biol Sci Med Sci. 2009;64:940-8.
137. Murphy KT, Koopman R, Naim T, Léger B, Trieu J, Ibebunjo C, et al. Antibody-directed myostatin inhibition in 21-mo-old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function. FASEB J. 2010;24:4433-42.
138. Amirouche A, Durieux AC, Banzet S, Koulmann N, Bonnefoy R, Mouret C, et al. Down-regulation of Akt/mammalian target of rapamycin signaling pathway in response to myostatin overexpression in skeletal muscle. Endocrinology. 2009;150:286-94.
139. McFarlane C, Plummer E, Thomas M, Hennebry A, Ashby M, Ling N, et al. Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF-κB-independent, FoxO1-dependent mechanism. J Cell Physiol. 2006;209:501-14.
140. Chelh I, Meunier B, Picard B, Reecy JM, Chevalier C, Hocquette JF, et al. Molecular profile of quadriceps muscle in myostatin-null mice reveal PI3K and apoptotic pathways as myostatin targets. BMC Genomics. 2009;10:196.
141. Costelli P, Muscaritoli M, Bonetto A, Penna F, Reffo P, Bossola M, et al. Muscle myostatin signaling is enhanced in experimental cancer cachexia. Eur J Clin Invest. 2008;38:531-8.
142. Petraglia F, Florio P, Luisi S, Gallo R, Gadducci A, Viganó P, et al. Expression and secretion of inhibin and activin A in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma. J Clin Endocrinol Metab. 1998;83:1194-200.
143. Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, et al. Induction of cachexia in mice by systemically administered myostatin. Science. 2002;296:1486-8.
144. Sharma M, Kambadur R, Matthews KG, Somers WG, Devlin GP, Conaglen JV, et al. Myostatin, a transforming growth factorbeta superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct. J Cell Physiol. 1999;180:1-9.
145. Shyu KG, Lu MJ, Wang BW, Sun HY, Chang H. Myostatin expression in ventricular myocardium in a rat model of volumeoverload heart failure. Eur J Clin Invest. 2006;36:713-9.
146. Heineke J, Auger-Messier M, Xu J, Sargent M, York A, Welle S, et al. Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure. Circulation. 2010;121:419-25.
147. Testelmans D, Crul T, Maes K, Agten A, Comach M, Decramer M, et al. Atrophy and hypertrophy signaling in the diaphragm of patients with COPD. Eur Respir J. 2010;35:549-56.
148. Hayot M, Rodriguez J, Vernus B, Carnac G, Jean E, Allen D, et al. Myostatin up-regulation is associated with the skeletal muscle response to hypoxic stimuli. Mol Cell Endocrinol. 2011;332:38-47.
149. Zhou X, Wang JL, Lu J, Song Y, Kwak KS, Jiao Q, et al. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell. 2010;142:531-43.
150. Klimek MEB, Aydogdu T, Link MJ, Pons M, Koniaris LG, Zimmers TA. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia. Biochem Biophys Res Commun. 2010;391:1548-54.
151. Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN, et al. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci USA. 2005;102:18117-22.
152. Roubenoff R. Catabolism of aging: is it an inflammatory process? Curr Opin Clin Nutr Metab Care. 2003;6:295-9.
153. Schaap LA, Pluijim SMF, Deeg DJH, Harris TB, Kritchevsky SB, Newman, et al. Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci. 2009;64A:1183-9.
154. Rieu I, Magne H, Savary-Auzeloux I, Averous J, Bos C, Peyron MA, et al. Reduction of low grade inflammation restores blunting of postprandial muscle anabolism and limits sarcopenia in old rats. J Physiol. 2009;587:5483-92.
155. Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev. 2009;8:18-30.
156. Reid MB, Li YP. Tumor necrosis factor-α and muscle wasting: a cellular perspective. Respir Res. 2001;2:269-72.
157. Aoi W, Sakuma K. Oxidative stress and skeletal muscle dysfunction with aging. Curr Aging Sci. 2011;4:101-9.
158. Meng S-J, Yu L-J. Oxidative stress, molecular inflammation and sarcopenia. Int J Mol Sci. 2010;11:1509-26.
159. Bar-Shai M, Carmeli E, Coleman R, Rozen N, Perek S, Euchs D, et al. The effect of hindlimb immobilization on acid phosphatase, metalloproteinase and nuclear factor-kappaB in muscles of young and old rats. Mech Ageing Dev. 2005;126:289-97.
160. Phillips T, Leeuwenburgh C. Muscle fiber-specific apoptosis and TNF-α signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J. 2005;19:668-70.
161. Marzetti E, Carter CS, Wohlgemuth SE, Lees HA, Giovannini S, Anderson B, et al. Changes in IL-15 expression and deathreceptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction. Mech Ageing Dev. 2009;130:272-80.
162. Pistilli E, Jackson JR, Always SE. Death receptor-associated proapoptotic signaling in aged skeletal muscle. Apoptosis. 2006;11:2115-26.
163. Argilés JM, Busquets S, Toledo M, López-Soriano FJ. The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care. 2009;3:263-8.
164. Malik ST, Naylor MS, East N, Oliff A, Balkwill FR. Cells secreting tumour necrosis factor show enhanced metastasis in nude mice. Eur J Cancer. 1990;26:1031-4.
165. Moresi V, Pristera A, Scicchitano BM, Molinaro M, Teodori L, Sassoon D, et al. Tumor necrosis factor-α inhibition of skeletal muscle regeneration is mediated by a caspase-dependent stem cell response. Stem Cells. 2008;26:997-1008.
166. Coletti D, Moresi V, Adamo S, Molinaro M, Sassoon D. Tumor necrosis factor-alpha gene transfer induces cachexia and inhibits muscle regeneration. Genesis. 2005;43:120-8.
167. Guttridge DC, Mayo MW, Madrid LV, Wang CY, Baldwin Jr AS. NF-κB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science. 2000;289:2363-6.
168. Di Marco S, Mazroui R, Dallaire P, Chittur S, Tenenbaum SA, Radzioch D, et al. NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release. Mol Cell Biol. 2005;25:6533-45.
169. Costelli P, Muscaritoli M, Bossola M, Moore-Carrasco R, Crepaldi S, Grieco G, et al. Skeletal muscle wasting in tumorbearing rats is associated with MyoD down-regulation. Int J Oncol. 2005;26:1663-8.
170. Remels AH, Gosker HR, Schrauwen P, Hommelberg PP, Sliwinski P, Polkey M, et al. TNF-alpha impairs regulation of muscle oxidative phenotype: implication for cachexia? FASEB J. 2010;24:5052-62.
171. Wysong A, Couch M, Shadfar S, Li L, Rodriguez JE, Asher S, et al. NF-κB inhibition protects against tumor-induced cardiac atrophy in vivo. Am J Pathol. 2011;178:1059-68.
172. Acharyya S, Butchbach ME, Sahenk Z, Wang H, Saji M, Carathers M, et al. Dystrophin glycoprotein complex dysfunction: a regulatory link between muscular dystrophy and cancer cachexia. Cancer Cell. 2005;8:421-32.
173. Kawamura I, Morishita R, Tomita N, Lacey E, Aketa M, Tsujimoto S, et al. Intratumoral injection of oligonucleotides to the NF-κB binding site inhibits cachexia in a mouse tumor model. Gene Ther. 1999;6:91-7.
174. Mastrocola R, Reffo P, Penna F, Tomasinelli CE, Boccuzzi G, Baccino FM, et al. Muscle wasting in diabetic and in tumorbearing rats: role of oxidative stress. Free Radical Biol Med. 2008;44:584-93.
175. Doucet M, Russell AP, Léger B, Debigaré R, Joanisse DR, Caron MA, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;176:261-9.
176. Adams V, Nehrhoff B, Späte U, Linke A, Schulze PC, Baur A, et al. Induction of iNOS-expression in skeletal muscle by IL-1β and NFκB activation: an in vitro and in vivo study. Cardiovasc Res. 2002;54:95-104.
177. Yu Z, Li P, Zhang M, Hannink M, Stamler JS, Yan Z. Fiber typespecific nitric oxide protects oxidative myofibers against cachectic stimuli. PLoS One. 2008;3:e2086.
178. Todorov PT, Cariuk P, McDevitt T, Coles B, Fearon K, Tisdale M. Characterization of a cancer cachectic factor. Nature. 1996;379:739-42.
179. Cariuk P, Lorite MJ, Todorov PT, Field WN, Wigmore SJ, Tisdale MJ. Induction of cachexia in mice by a product isolated from the uterine of cachectic cancer patients. Br J Cancer. 1997;76:606-13.
180. Tisdale MJ. Molecular pathways leading to cancer cachexia. Physiology (Bethesda). 2005;20:340-8.
181. Wyke SM, Tisdale MJ. NF-κB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin-proteasome system in skeletal muscle. Br J Cancer. 2005;92:711-21.
182. Marzetti E, Hwang JC, Lees HA, Wohlgemuth SE, Dupont-Versteegden EE, Carter CS, et al. Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochim Biophys Acta, Gen Subj. 2009;1800:235-44.
183. Dupont-Versteegden EE. Apoptosis in muscle atrophy: relevance to sarcopenia. Exp Gerontol. 2005;40:473-81.
184. Marzetti E, Lawler JM, Hiona A, Manini T, Seo AY, Leeuwenburgh C. Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle. Free Radic Biol Med. 2008;44:160-8.
185. Wang C, Youle RJ. The role of mitochondria in apoptosis. Ann Rev Genet. 2009;43:95-118.
186. Song W, Kwak HB, Lawler JM. Exercise training attenuates ageinduced changes in apoptotic signaling in rat skeletal muscle. Antioxid Redox Signal. 2006;8:517-28.
187. Pollack M, Leeuwenburgh C. Apoptosis and aging: role of the mitochondria. J Gerontol A Biol Sci Med Sci. 2001;56:B475-82.
188. Jezek P, Hlavata L. Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int J Biochem Cell Biol. 2005;37:2478-503.
189. Yakes FM, Van HB. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA. 1997;94:514-9.
190. Bua EA, McKiernan SH, Eanagat J, McKenzie D, Aiken JM. Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia. J Appl Physiol. 2002;92:2617-24.
191. Wanagat J, Cao Z, Pathare P, Aiken JM. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. FASEB J. 2001;15:322-32.
192. Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood). 2002;227:671-82.
193. Argiles JM, Lopez-Soriano FJ, Busquets S. Apoptosis signaling is essential and precedes protein degradation in wasting skeletal muscle during catabolic conditions. Int J Biochem Cell Biol. 2008;40:1674-8.
194. Baker DJ, Hepple RT. Elevated caspase and AIDF gene expression correlate with progression of sarcopenia during aging in male F344BN rats. Exp Gerontol. 2006;41:1149-56.
195. Park SY, Kim HY, Lee JH, Yoon KH, Change MS, Park SK. The age-dependent induction of apoptosis-inducing factor (AIF) in the human semitendinosus skeletal muscle. Cell Mol Biol Lett. 2010;15:1-12.
196. Busquets S, Figueras M, Fuster G, Almendro V, Moore-Carrasco R, Ametller E, et al. Anticachectic effects of formoterol: a drug for potential treatment of muscle wasting. Cancer Res. 2004;64:6725-31.
197. Kataoka T, Budd RC, Holler N, Thome M, Martinon F, Irmler M, et al. The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways. Curr Biol. 2000;10:640-8.
198. Micheau O, Lens S, Gaide O, Alevizopoulos K, Tschopp J. NFkappaB signals induce the expression of c-FLIP. Mol Cell Biol. 2001;21:5299-305.
199. Yeh WC, Shahinian A, Speiser D, Kraunus J, Billia F, Wakeham A, et al. Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity. 1997;7:715-25.
200. Wajant H, Haas E, Schwenzer R, Muhlenbeck F, Kreuz S, Schubert G, et al. Inhibition of death receptor-mediated gene induction by a cycloheximide-sensitive factor occurs at the level of or upstream of Fas-associated death domain protein (FADD). J Biol Chem. 2000;275:24357-66.
201. Jiang Z, Clemens PR. Cellular caspase-8-like inhibitory protein (cFLIP) prevents inhibition of muscle cell differentiation induced by cancer cells. FASEB J. 2006;20:E1979-89.
202. Daniel NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116:205-19.
203. Hermann M, Berger P. Hormonal changes in aging men: a therapeutic indication? Exp Gerontol. 2001;36:1075-82.
204. Kamel H, Maas D, Duthie E. Role of hormones in the pathogenesis and management of sarcopenia. Drugs Aging. 2002;19:869-77.
205. Ryall JG, Schertzer JD, Lynch GS. Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology. 2008;9:213-28.
206. Szulc P, Duboeuf F, Marchand F, Delmas PD. Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: the MINOS Study. Am J Clin Nutr. 2004;80:496-503.
207. Tenover JL. Testosterone and the aging male. J Androl. 1997;18:103-6.
208. Ferrucci L, Penninx BW, Volpato S, Harris TB, Bandeen-Roche K, Balfour J, et al. Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc. 2002;50:1947-54.
209. Philippou A, Maridaki M, Halapas A, Koutsilieris M. The role of the insulin-like growth factor-I (IGF-I) in skeletal muscle physiology. In Vivo. 2007;21:45-54.
210. Butterfield GE, Thompson J, Rennie MJ, Marcus R, Hintz RL, Hoffman AR. Effect of thGH and rhIGF-I treatment on protein utilization in elderly women. Am J Physiol Endocrinol Metab. 1997;272:E94-9.
211. Giovannini S, Marzetti E, Borst SE, Leeuwenburgh C. Modulation of GH/IGF-I axis: potential strategies to counteract sarcopenia in older adults. Mech Ageing Dev. 2008;129:593-601.
212. EvansWJ, Paolisso G, Abbatecola AM, Corsonello A, Bustacchini S, Strollo F, et al. Frailty and muscle metabolism dysregulation in the elderly. Biogerontology. 2010;11:527-36.
213. Dardevet D, Sornet C, Attaix D, Baracos VE, Grizard J. Insulinlike growth factor-I and insulin resistance in skeletal muscles of adults. Endocrinology. 1994;134:1475-84.
214. Martineau LC, Chadan SG, Parkhouse WS. Age-associated alterations in cardiac and skeletal muscle glucose transporters, insulin and IGF-I receptors, and PI3-kinase protein contents in the C57BL/6 mouse. Mech Ageing Dev. 1999;106:217-32.
215. Arvat E, Broglio F, Ghigo E. Insulin-like growth factor I: implication in aging. Drugs Aging. 2000;16:29-40.
216. Marcell TJ, Harman SM, Urban RJ, Metz DD, Rodgers BD, Blaskman MR. Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men. Am J Physiol Endocrinol Metab. 2001;281:E1159-64.
217. Wilkes EA, Selby AL, Atherton PJ, Patel R, Rankin D, Smith K, et al. Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia. Am J Clin Nutr. 2009;90:1343-50.
218. Bakhshi V, Elliott M, Gentili A, Godschalk M, Mulligan T. Testosterone improves rehabilitation outcomes in ill older men. J Am Geriatr Soc. 2000;48:550-3.
219. Ferrando AA, Sheffield-Moore M, Yeckel CW, Gilkison C, Jiang J, Achacosa A, et al. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab. 2002;282:E601-7.
220. Morley JE, Perry 3rd HM. Androgen deficiency in aging men: role of testosterone replacement therapy. J Lab Clin Med. 2000;135:370-8.
221. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab. 1999;84:2647-53.
222. Bhasin S, Calof O, Storer TW, LeeM, Mazer N, Jasuja R, et al. Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for physical dysfunction in chronic illness and ageing. Nat Clin Pract Endocrinol Metab. 2006;2:146-59.
223. Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab. 2006;91:3024-33.
224. Kovacheva EL, Hikim AP, Shen R, Sinha I, Sinha-Hikim I. Testosterone supplementation reverses sarcopenia in aging through regulation ofmyostatin, c-JunNH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology. 2010;151:628-38.
225. Chebowski RT, Heber D. Hypogonadism in male patients with metastatic cancer prior to chemotherapy. Cancer Res. 1982;42:2495-8.
226. Zitzmann M, Nieschlag E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol. 2000;161:73-88.
227. Crul T, Spruit MA, Gayan-Ramirez G, Quarck R, Gosselink R, Troosters T, et al. Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients. Eur J Clin Invest. 2007;37:897-904.
228. Debigare R, Marquis K, Cote CH, Tremblay RR, Michaud A, LeBlanc P, et al. Catabolic/anabolic balance and muscle wasting in patients with COPD. Chest. 2003;124:83-9.
229. Kamischke A, Kemper DE, Castel MA, Luthke M, Rolf C, Behre HM, et al. Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy. Eur Respir J. 1998;11:41-5.
230. Anker SD, Volterrani M, Pflaum CD, Strasburger CJ, Osterziel KJ, Doehner W, et al. Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone. J Am Coll Cardiol. 2001;38:443-52.
231. Niebauer J, Pflaum CD, Clark AL, Strasburger CJ, Hooper J, Poole-Wilson PA, et al. Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation. J Am Coll Cardiol. 1998;32:393-7.
232. Ng EH, Rock CS, Lazarus DD, Stiaino-Coico L, Moldawer LL, Lowry SF. Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia. Am J Physiol. 1992;262:R426-31.
233. Denson LA, Menon RK, Shaufl A, Bajwa HS, Williams CR, Karpen SJ. TNF-alpha downregulates murine hepatic growth hormone receptor expression by inhibiting Sp1 and Sp3 binding. J Clin Invest. 2001;107:1451-8.
234. Casaburi R, Bhasin S, Cosentino L, Porszasz J, Somfay A, Lewis MI, et al. Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;170:870-8.
235. Knapp PE, Storer TW, Herbst KL, Singh AB, Dzekov C, Dzekov J, et al. Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. Am J Physiol Endocrinol Metab. 2008;294:E1135-43.
236. Mulligan K, Zackin R, Von Roenn JH, Chesney MA, Egorin MJ, Sattler FR, et al. Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus associated weight loss: a randomized, double-blind, placebo-controlled, multicenter trial. J Clin Endocrinol Metab. 2007;92:563-70.
237. Pape GS, Friedman M, Underwood LE, Clemmons DR. The effect of growth hormone on weight gain and pulmonary function in patients with chronic obstructive lung disease. Chest. 1991;99:1495-500.
238. Burdet L, de Muralt B, Schutz Y, Pichard C, Fitting JW. Administration of growth hormone to underweight patients with chronic obstructive pulmonary disease. A prospective, randomized, controlled study. Am J Respir Crit Care Med. 1997;156:1800-6.
239. Frustaci A, Gentiloni N, Russo MA. Growth hormone in the treatment of dilated cardiomyopathy. NEngl J Med. 1996;335:672-3.
240. Osterziel KJ, Strohm O, Schuler J, Friedrich M, Hänlein D, Willenbrock R, et al. Randomised, double blind, placebocontrolled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy. Lancet. 1998;351:1233-7.
241. Gullett NP, Hebbar G, Ziegler TR. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting. Am J Clin Nutr. 2010;91:1143S-7S.
242. Akamizu T, Kangawa K. Ghrelin for cachexia. J Cachexia Sarcopenia Muscle. 2010;1:169-76.
243. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005;85:495-522.
244. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, Palaniappan R, et al. Ghrelin inhibits leptin-and activationinduced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest. 2004;114:57-66.
245. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86:5992.
246. Russell ST, Tisdale MJ. The role of glucocorticoids in the induction of zinc-α2-glycoprotein expression in adipose tissue in cancer cachexia. Br J Cancer. 2005;92:876-81.
247. Tessitore L, Costelli P, Baccino FM. Pharmacological interference with tissue hypercatabolism in tumour-bearing rats. Biochem J. 1994;299:71-8.
248. Hasselgren PO. Glucocorticoids and muscle metabolism. Curr Opin Clin Nutr Metab Care. 1999;2:201-5.
249. Gilson H, Schakman O, Combaret L, Lause P, Grobet L, Attaix D, et al. Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology. 2007;148:452-60.
250. von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle. J Cachexia Sarcopenia Muscle. 2010;1:7-8.