Advanced search
Publication Cover
Expert Opinion on Emerging Drugs Volume 13, 2008 - Issue 4
Submit an article Journal homepage
606
Views
26
CrossRef citations to date
0
Altmetric
Review

Update on emerging drugs for sarcopenia – age-related muscle wasting

Gordon S Lynch Professor The University of Melbourne, Department of Physiology, Basic and Clinical Myology Laboratory, Victoria 3010, Australia +61 3 8344 0065; +61 3 8344 5818; [email protected]
Pages 655-673 | Published online: 02 Dec 2008

Bibliography

  • Ryall JG, Schertzer JD, Lynch GS. Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology 2008;9:213-28
  • Alway SE, Siu PM. Nuclear apoptosis contributes to sarcopenia. Exerc Sport Sci Rev 2008;36:51-7
  • Chabi B, Ljubicic V, Menzies KJ, et al. Mitochondrial function and apoptotic susceptibility in aging skeletal muscle. Aging Cell 2008;7:2-12
  • Marzetti E, Wohlgemuth SE, Lees HA, et al. Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle. Mech Ageing Dev 2008;129:542-9
  • Hidestrand M, Richards-Malcolm S, Gurley CM, et al. Sca-1-expressing nonmyogenic cells contribute to fibrosis in aged skeletal muscle. J Gerontol A Biol Sci Med Sci 2008;63:566-79
  • Edström E, Altun M, Hägglund 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
  • Clavel S, Coldefy AS, Kurkdjian E, et al. Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat tibialis anterior muscle. Mech Ageing Dev 2006;127:794-801
  • Raue U, Slivka D, Jemiolo B, et al. Proteolytic gene expression differs at rest and after resistance exercise between young and old women. J Gerontol A Biol Sci Med Sci 2007;62:1407-12
  • Lynch GS. Novel therapies for sarcopenia: ameliorating age-related changes in skeletal muscle. Expert Opin Ther Patents 2002;12:11-27
  • Lynch GS. Emerging drugs for sarcopenia: age-related muscle wasting. Expert Opin Emerg Drugs 2004;9:345-61
  • Solomon AM, Bouloux PM. Modifying muscle mass - the endocrine perspective. J Endocrinol 2006;191:349-60
  • Brack AS, Rando TA. Intrinsic changes and extrinsic influences of myogenic stem cell function during aging. Stem Cell Rev 2007;3:226-37
  • Degens H. Age-related skeletal muscle dysfunction: causes and mechanisms. J Musculoskelet Neuronal Interact 2007;7:246-52
  • Edström E, Altun M, Bergman E, et al. Factors contributing to neuromuscular impairment and sarcopenia during aging. Physiol Behav 2007;92:129-35
  • Faulkner JA, Larkin LM, Claflin DR, Brooks SV. Age-related changes in the structure and function of skeletal muscles. Clin Exp Pharmacol Physiol 2007;34:1091-6
  • Lee CE, McArdle A, Griffiths RD. The role of hormones, cytokines and heat shock proteins during age-related muscle loss. Clin Nutr 2007;26:524-534
  • Thomas DR. Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia. Clin Nutr 2007;26:389-99
  • Hagen JL, Krause DJ, Baker DJ, et al. Skeletal muscle aging in F344BN F1-hybrid rats: I. Mitochondrial dysfunction contributes to the age-associated reduction in VO2max. J Gerontol A Biol Sci Med Sci 2004;59:1099-100
  • Hepple RT, Baker DJ, McConkey M, et al. Caloric restriction protects mitochondrial function with aging in skeletal and cardiac muscles. Rejuvenation Res 2006;9:219-22
  • Runge M, Rittweger J, Russo CR, et al. Is muscle power output a key factor in the age-related decline in physical performance? A comparison of muscle cross section, chair-rising test and jumping power. Clin Physiol Funct Imaging 2004;24:335-40
  • Korhonen MT, Cristea A, Alén M, et al. Aging, muscle fiber type, and contractile function in sprint-trained athletes. J Appl Physiol 2006;101:906-17
  • Cristea A, Korhonen MT, Häkkinen K, et al. Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single-fibre levels in elite master sprinters. Acta Physiol 2008;193:275-89
  • Montero-Odasso M, Duque G. Vitamin D in the aging musculoskeletal system: an authentic strength preserving hormone. Mol Aspects Med 2005;26:203-19
  • Hamid Z, Riggs A, Spencer T, et al. Vitamin D deficiency in residents of academic long-term care facilities despite having been prescribed vitamin D. J Am Med Dir Assoc 2007;8:71-5
  • Brodsky IG, Balagopal P, Nair KS. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men: a clinical research center study. J Clin Endocrinol Metab 1996;81:3469-75
  • Bhasin S, Storer TW, Berman N, et al. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab 1997;82:407-13
  • Bhasin S, Javanbakht M. Can androgen therapy replete lean body mass and improve muscle function in wasting associated with human immunodeficiency virus infection? JPEN J Parenter Enteral Nutr 1999;23:S195-201
  • Snyder PJ, Peachey H, Hannoush P, 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
  • Ferrando AA, Sheffield-Moore M, et al. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 2002;282:E601-7
  • Frisoli A Jr, Chaves PH, Pinheiro MM, Szejnfeld VL. The effect of nandrolone decanoate on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis: a double-blind, randomized, placebo-controlled clinical trial. J Gerontol A Biol Sci Med Sci 2005;60:648-53
  • Bhasin S, Storer TW, Berman N, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 1996;335:1-7
  • Fairfield WP, Treat M, Rosenthal DI, et al. Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting. J Appl Physiol 2001;90:2166-71
  • Sih R, Morley JE, Kaiser FE, et al. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 1997;82:1661-7
  • Schroeder ET, Terk M, Sattler FR. Androgen therapy improves muscle mass and strength but not muscle quality: results from two studies. Am J Physiol Endocrinol Metab 2003;285:E16-24
  • Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 2008;299:39-52
  • Storer TW, Woodhouse L, Magliano L, et al. Changes in muscle mass, muscle strength, and power but not physical function are related to testosterone dose in healthy older men. J Am Geriatr Soc 2008;(in press, Sep 15)
  • Lynch GS. Tackling Australia's future health problems: developing strategies to combat sarcopenia – age-related muscle wasting and weakness. Int Med J 2004;34:294-6
  • 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
  • Schaap LA, Pluijm SM, Deeg DJ, Visser M. Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med 2006;119(526):e9-17
  • Abbatecola AM, Paolisso G. Is there a relationship between insulin resistance and frailty syndrome? Curr Pharm Des 2008;14:405-10
  • Morley JE. Diabetes, sarcopenia, and frailty. Clin Geriatr Med 2008;24:455-69
  • Prado CM, Lieffers Jr, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 2008;9:629-35
  • Topinková E. Aging, disability and frailty. Ann Nutr Metab 2008;52(Suppl 1):6-11
  • Aronow WS, Frishman WH, Cheng-Lai A. Cardiovascular drug therapy in the elderly. Cardiol Rev 2007;15:195-215
  • 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
  • Thompson DD. Aging and sarcopenia. J Musculoskelet Neuronal Interact 2007;7:344-5
  • Gordon T, Hegedus J, Tam SL. Adaptive and maladaptive motor axonal sprouting in aging and motoneuron disease. Neurol Res 2004;26:174-85
  • Lynch GS, Shavlakadze T, Grounds MD. Evaluation of therapies to reduce age-related skeletal muscle wasting. In: Rattan S, edition, Aging Interventions and Therapies, 2005; p. 63-84. World Scientific Publishers, Singapore
  • Lynch GS, Schertzer JD, Ryall JG. Therapeutic approaches for muscle wasting disorders. Pharmacol Ther 2007;113:461-87
  • Libera LD, Vescovo G. Muscle wastage in chronic heart failure, between apoptosis, catabolism and altered anabolism: a chimaeric view of inflammation? Curr Opin Clin Nutr Metab Care 2004;7:435-41
  • Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 2005;37:1974-84
  • Ventadour S, Attaix D. Mechanisms of skeletal muscle atrophy. Curr Opin Rheumatol 2006;18:631-5
  • Bassel-Duby R, Olson EN. Signaling pathways in skeletal muscle remodeling. Annu Rev Biochem 2006;75:19-37
  • Kandarian SC, Jackman RW. Intracellular signaling during skeletal muscle atrophy. Muscle Nerve 2006;33:155-65
  • Zhao J, Brault JJ, Schild A, et al. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 2007;6:472-83
  • Lynch GS, Ryall JG. Role of β-adrenoceptor signaling in skeletal muscle: implications for muscle wasting and disease. Physiol Rev 2008;88:729-67
  • Sandri M. Signaling in muscle atrophy and hypertrophy. Physiology 2008;23:160-70
  • Frostick S, Yin Q, Kemp G. Schwann cells, neurotrophic factors, and peripheral nerve regeneration. Microsurgery 1998;18:397-405
  • Stuerenburg HJ, Kunze K. Tissue concentrations of nerve growth factor in aging rat heart and skeletal muscle. Muscle Nerve 1998;21:404-6
  • Keller-Peck CR, Feng G, Sanes Jr, et al. cell line-derived neurotrophic factor administration in postnatal life results in motor unit enlargement and continuous synaptic remodeling at the neuromuscular junction. J Neurosci 2001;21:6136-46
  • Funakoshi H, Belluardo N, Arenas E, et al. Muscle-derived neurotropin-4 as an activity-dependent trophic signal for adult motor neurons. Science 1995;268:1495-9
  • Gomez-Pinilla F, Ying Z, Opazo P, et al. Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur J Neurosci 2001;13:1078-84
  • Frischknecht R, Fejtova A, Viesti M, et al. Activity-induced synaptic capture and exocytosis of the neuronal serine protease neurotrypsin. J Neurosci 2008;28:1568-79
  • Stephan A, Mateos JM, Kozlov SV, et al. Neurotrypsin cleaves agrin locally at the synapse. FASEB J 2008;22:1861-73
  • Fraysse B, Guillet C, Huchet-Cadiou C, et al. Ciliary neurotrophic factor prevents unweighting-induced functional changes in rat soleus muscle. J Appl Physiol 2000;88:1623-30
  • Mousavi K, Miranda W, Parry DJ. Neurotrophic factors enhance the survival of muscle fibers in EDL, but not SOL, after neonatal nerve injury. Am J Physiol 2002;283:C950-9
  • Mitsumoto H, Ikeda K, Holmlund T, et al. The effects of ciliary neurotrophic factor on motor dysfunction in wobbler mouse motor neuron disease. Ann Neurol 1994;36:142-8
  • Zhang J, Lineaweaver WC, Oswald T, et al. Ciliary neurotrophic factor for acceleration of peripheral nerve regeneration: an experimental study. J Reconstr Microsurg 2004;20:323-37
  • Ettinger MP, Littlejohn TW, Schwartz SL, et al. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized, dose-ranging study. JAMA 2003;289:1826-32
  • Watt MJ, Dzamko N, Thomas WG, et al. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 2006;12:541-8
  • Liu QS, Gao M, Zhu SY, et al. The novel mechanism of recombinant human ciliary neurotrophic factor on the anti-diabetes activity. Basic Clin Pharmacol Toxicol 2007;101:78-84
  • Crowe S, Turpin SM, Ke F, et al. Metabolic remodeling in adipocytes promotes ciliary neurotrophic factor-mediated fat loss in obesity. Endocrinology 2008;149:2546-56
  • Steinberg GR, Jørgensen SB. The AMP-activated protein kinase: role in regulation of skeletal muscle metabolism and insulin sensitivity. Mini Rev Med Chem 2007;7:519-26
  • Matthews VB, Febbraio MA. CNTF: a target therapeutic for obesity-related metabolic disease? J Mol Med 2008;86:353-61
  • Fishburn CS. The pharmacology of PEGylation: Balancing PD with PK to generate novel therapeutics. J Pharm Sci 2008;97:4167-83
  • Youn YS, Chae SY, Lee S, et al. Evaluation of therapeutic potentials of site-specific PEGylated glucagon-like peptide-1 isomers as a type 2 anti-diabetic treatment: Insulinotropic activity, glucose-stabilizing capability, and proteolytic stability. Biochem Pharmacol 2007;73:84-93
  • Chae SY, Jin CH, Shin HJ, et al. Preparation, characterization, and application of biotinylated and biotin-PEGylated glucagon-like peptide-1 analogues for enhanced oral delivery. Bioconjug Chem 2008;19:334-41
  • Thanos CG, Bell WJ, O'Rourke P, et al. Sustained secretion of ciliary neurotrophic factor to the vitreous, using the encapsulated cell therapy-based NT-501 intraocular device. Tissue Eng 2004;10:1617-22
  • Sieving PA, Caruso RC, Tao W, et al. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci USA 2006;103:3896-901
  • TAO W. Application of encapsulated cell technology for retinal degenerative diseases. Expert Opin Biol Ther 2006;6:717-26
  • Kent TL, Glybina IV, Abrams GW, Iezzi R. Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat. Invest Ophthalmol Vis Sci 2008;49:372-9
  • Rhee KD, Ruiz A, Duncan JL, et al. Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa. Invest Ophthalmol Vis Sci 2007;48:1389-400
  • Rathbone MP, Middlemiss PJ, Crocker CE, et al. AIT-082 as a potential neuroprotective and regenerative agent in stroke and central nervous system injury. Expert Opin Investig Drugs 1999;8:1255-62
  • Jiang S, Khan MI, Middlemiss PJ, et al. AIT-082 and methylprednisolone singly, but not in combination, enhance functional and histological improvement after acute spinal cord injury in rats. Int J Immunopathol Pharmacol 2004;17:353-66
  • Nannan G, Runmei Y, Fusheng L, et al. Effects of AIT-082, a purine derivative, on tremor induced by arecoline or oxotremorine in mice. Pharmacology 2007;80:21-6
  • Ewing JF, Maines MD. Regulation and expression of heme oxygenase enzymes in aged-rat brain: age related depression in HO-1 and HO-2 expression and altered stress-response. J Neural Transm 2006;113:439-54
  • Calcutt NA, Freshwater JD, Hauptmann N, et al. Protection of sensory function in diabetic rats by Neotrofin. Eur J Pharmacol 2006;534:187-93
  • Visanji NP, Orsi A, Johnston TH, et al. PYM50028, a novel, orally active, nonpeptide neurotrophic factor inducer, prevents and reverses neuronal damage induced by MPP+ in mesencephalic neurons and by MPTP in a mouse model of Parkinson's disease. FASEB J 2008;22:2488-97
  • Thurmond J, Butchbach ME, Palomo M, et al. Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy. J Med Chem 2008;51:449-69
  • Ralph GS, Binley K, Wong LF, et al. Gene therapy for neurodegenerative and ocular diseases using lentiviral vectors. Clin Sci 2006;110:37-46
  • Wong LF, Goodhead L, Prat C, et al. Lentivirus-mediated gene transfer to the central nervous system: therapeutic and research applications. Hum Gene Ther 2006;17:1-9
  • Azzouz M, Mazarakis N. Non-primate EIAV-based lentiviral vectors as gene delivery system for motor neuron diseases. Curr Gene Ther 2004;4:277-86
  • Azzouz M, Le T, Ralph GS, et al. Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy. J Clin Invest 2004;114:1726-31
  • Azzouz M, Kingsman SM, Mazarakis ND. Lentiviral vectors for treating and modeling human CNS disorders. J Gene Med 2004;6:951-62
  • Didonato CJ, Parks RJ, Kothary R. Development of a gene therapy strategy for the restoration of survival motor neuron protein expression: implications for spinal muscular atrophy therapy. Hum Gene Ther 2003;14:179-88
  • Bowerman M, Shafey D, Kothary R. Smn depletion alters profilin II expression and leads to upregulation of the RhoA/ROCK pathway and defects in neuronal integrity. J Mol Neurosci 2007;32:120-31
  • Setola V, Terao M, Locatelli D, et al. Axonal-SMN (a-SMN), a protein isoform of the survival motor neuron gene, is specifically involved in axonogenesis. Proc Natl Acad Sci USA 2007;104:1959-64
  • Alekshun MN. New advances in antibiotic development and discovery. Expert Opin Investig Drugs 2005;14:117-34
  • Bordet T, Buisson B, Michaud M, et al. Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J Pharmacol Exp Ther 2007;322:709-20
  • Jarecki J, Chen X, Bernardino A, et al. Diverse small-molecule modulators of SMN expression found by high-throughput compound screening: early leads towards a therapeutic for spinal muscular atrophy. Hum Mol Genet 2005;14:2003-18
  • Maurer MH, Schäbitz WR, Schneider A. Old friends in new constellations – the hematopoetic growth factors G-CSF, GM-CSF, and EPO for the treatment of neurological diseases. Curr Med Chem 2008;15:1407-11
  • Escher P, Lacazette E, Courtet M, et al. Synapses form in skeletal muscles lacking neuregulin receptors. Science 2005;308:1920-3
  • Trachtenberg JT, Thompson WJ. Nerve terminal withdrawal from rat neuromuscular junctions induced by neuregulin and Schwann cells. J Neurosci 1997;17:6243-55
  • Jaworski A, Burden SJ. Neuromuscular synapse formation in mice lacking motor neuron- and skeletal muscle-derived Neuregulin-1. J Neurosci 2006;26:655-61
  • Britsch S. The neuregulin-I/ErbB signaling system in development and disease. Adv Anat Embryol Cell Biol 2007;190:1-65
  • Brinkmann BG, Agarwal A, Sereda MW, et al. Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system. Neuron 2008;59:581-95
  • Zanazzi G, Einheber S, Westreich R, et al. Glial growth factor/neuregulin inhibits Schwann cell myelination and induces demyelination. J Cell Biol 2001;152:1289-99
  • Penderis J, Woodruff RH, Lakatos A, et al. Increasing local levels of neuregulin (glial growth factor-2) by direct infusion into areas of demyelination does not alter remyelination in the rat CNS. Eur J Neurosci 2003;18:2253-64
  • Dori A, Soreq H. Neuromuscular therapeutics by RNA-targeted suppression of ACHE gene expression. Ann NY Acad Sci 2006;1082:77-90
  • Brenner T, Hamra-Amitay Y, Evron T, et al. The role of readthrough acetylcholinesterase in the pathophysiology of myasthenia gravis. FASEB J 2003;17:214-22
  • Sussman JD, Argov Z, Mckee D, et al. Antisense treatment for myasthenia gravis: experience with monarsen. Ann NY Acad Sci 2008;1132:283-90
  • Inaba M, Saito H, Fujimoto M, et al. Suppressor of cytokine signaling 1 suppresses muscle differentiation through modulation of IGF-I receptor signal transduction. Biochem Biophys Res Commun 2005;328:953-61
  • Spangenburg EE. SOCS-3 induces myoblast differentiation. J Biol Chem 2005;280:10749-58
  • Spangenburg EE. Suppressor of cytokine signaling, skeletal muscle, and chronic health conditions: the potential interactions. Exerc Sport Sci Rev 2007;35:156-62
  • Trenerry MK, Carey KA, Ward AC, et al. Exercise-induced activation of STAT3 signaling is increased with age. Rejuvenation Res 2008;11:717-24
  • Léger B, Derave W, De Bock K, et al. Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. Rejuvenation Res 2008;11:163-175B
  • Frutos MG, Cacicedo L, Fernández C, et al. Insights into a role of GH secretagogues in reversing the age-related decline in the GH/IGF-I axis. Am J Physiol Endocrinol Metab 2007;293:E1140-52
  • Ferdinandi ES, Brazeau P, High K, et al. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic Clin Pharmacol Toxicol 2007;100:49-58
  • Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med 2007;357:2359-70
  • Falutz J, Allas S, Mamputu JC, et al. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS 2008;22:1719-28
  • Lynch GS, Schertzer JD, Ryall JG. Anabolic agents for improving muscle regeneration and function after injury. Clin Exp Pharmacol Physiol 2008;35:852-8
  • Vandenburgh H, Del Tatto M, Shansky J, et al. Tissue-engineered skeletal muscle organoids for reversible gene therapy. Hum Gene Ther 1996;7:2195-200
  • Vandenburgh H, Del Tatto M, Shansky J, et al. Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle. Hum Gene Ther 1998;9:2555-2264
  • Powell C, Shansky J, Del Tatto M, et al. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy. Hum Gene Ther 1999;10:565-77
  • Shansky J, Creswick B, Lee P, et al. Paracrine release of insulin-like growth factor 1 from a bioengineered tissue stimulates skeletal muscle growth in vitro Tissue Eng 2006;12:1833-41
  • Payumo FC, Kim HD, Sherling MA, et al. Tissue engineering skeletal muscle for orthopaedic applications. Clin Orthop Relat Res 2002;403(Suppl): S228-42
  • Musgrave DS, Pruchnic R, Bosch P, et al. Human skeletal muscle cells in ex vivo gene therapy to deliver bone morphogenetic protein-2. J Bone Joint Surg Br 2002;84:120-7
  • Vandenburgh H, Shansky J, Benesch-Lee F, et al. Drug-screening platform based on the contractility of tissue-engineered muscle. Muscle Nerve 2008;37:438-47
  • Landi F, Capoluongo E, Russo A, et al. Free insulin-like growth factor-I and cognitive function in older persons living in community. Growth Horm IGF Res 2007;17:58-66
  • Maggio M, Lauretani F, Ceda GP, et al. Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study. Arch Intern Med 2007;167:2249-54
  • Ceda GP, Dall'aglio E, Maggio M, et al. Clinical implications of the reduced activity of the GH-IGF-I axis in older men. J Endocrinol Invest 2005;28(Suppl):96-100
  • Goldspink G, Harridge SD. Growth factors and muscle ageing. Exp Gerontol 2004;39:1433-8
  • Shavlakadze T, Grounds M. Of bears, frogs, meat, mice and men: complexity of factors affecting skeletal muscle mass and fat. Bioessays 2006;28:994-1009
  • Woodhouse LJ, Mukherjee A, Shalet SM, Ezzat S. The influence of growth hormone status on physical impairments, functional limitations, and health-related quality of life in adults. Endocr Rev 2006;27:287-317
  • Williams RM, Mcdonald A, O'savage M, Dunger DB. Mecasermin rinfabate: rhIGF-I/rhIGFBP-3 complex: iPLEX. Expert Opin Drug Metab Toxicol 2008;4:311-24
  • Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3. Drugs R D 2005;6:120-7
  • Kemp SF, Fowlkes JL, Thrailkill KM. Efficacy and safety of mecasermin rinfabate. Expert Opin Biol Ther 2006;6:533-8
  • Clemmons DR, Sleevi M, Allan G, Sommer A. Effects of combined recombinant insulin-like growth factor (IGF)-I and IGF binding protein-3 in type 2 diabetic patients on glycemic control and distribution of IGF-I and IGF-II among serum binding protein complexes. J Clin Endocrinol Metab 2007;92:2652-8
  • Chernausek SD, Backeljauw PF, Frane J, et al. GH Insensitivity Syndrome Collaborative Group: Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab 2007;92:902-10
  • Keating GM. Mecasermin. BioDrugs 2008;22:177-88
  • Lee SJ, Mcpherron AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 2001;98:9306-11
  • Lee SJ. Quadrupling muscle mass in mice by targeting TGF-beta signaling pathways. PLoS ONE 2007;2:e789
  • Tsuchida K. Activins, myostatin and related TGF-beta family members as novel therapeutic targets for endocrine, metabolic and immune disorders. Curr Drug Targets Immune Endocr Metab Disord 2004;4:157-66
  • Tsuchida K. Targeting myostatin for therapies against muscle-wasting disorders. Curr Opin Drug Discov Devel 2008;11:487-94
  • Siriett V, Platt L, Salerno MS, et al. Prolonged absence of myostatin reduces sarcopenia. J Cell Physiol 2006;209:866-73
  • Siriett V, Salerno MS, Berry C, et al. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Mol Ther 2007;15:1463-70
  • Tsuchida K. Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer. Endocr J 2008;55:11-21
  • Nadeau A, Karpati G. Are big muscles necessarily good muscles? Ann Neurol 2008;63:543-5
  • Wagner KR, Fleckenstein JL, Amato AA, et al. A Phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy. Ann Neurol 2008;63:561-71
  • Gao W, Kearbey JD, Nair VA, et al. Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia. Endocrinology 2004;145:5420-8
  • Wilson EM. Muscle-bound? A tissue-selective nonsteroidal androgen receptor modulator. Endocrinology 2007;148:1-3
  • Page ST, Marck BT, Tolliver JM, Matsumoto AM. Tissue selectivity of the anabolic steroid, 19-nor-4-androstenediol-3β,17β-diol in male Sprague Dawley rats: selective stimulation of muscle mass and bone mineral density relative to prostate mass. Endocrinology 2008;149:1987-93
  • Chen J, Kim J, Dalton JT. Discovery and therapeutic promise of selective androgen receptor modulators. Mol Interv 2005;5:173-88
  • Bhasin S, Calof OM, Storer TW, et al. Drug insight: Testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab 2006;2:146-59
  • Cadilla R, Turnbull P. Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential. Curr Top Med Chem 2006;6:245-70
  • Gao W, Kim J, Dalton JT. Pharmacokinetics and pharmacodynamics of nonsteroidal androgen receptor ligands. Pharm Res 2006;23:1641-58
  • Omwancha J, Brown TR. Selective androgen receptor modulators: in pursuit of tissue-selective androgens. Curr Opin Investig Drugs 2006;7:873-81
  • Segal S, Narayanan R, Dalton JT. Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery. Expert Opin Investig Drugs 2006;15:377-87
  • Gao W, Dalton JT. Ockham's razor and selective androgen receptor modulators (SARMs): are we overlooking the role of 5alpha-reductase? Mol Interv 2007;7:10-13
  • Gao W, Dalton JT. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). Drug Discov Today 2007;12:241-248
  • Zhang X, Li X, Allan GF, et al. Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators. J Med Chem 2007;50:3857-69
  • Ostrowski J, Kuhns JE, Lupisella JA, et al. Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats. Endocrinology 2007;148:4-12
  • Li JJ, Sutton JC, Nirschl A, et al. Discovery of potent and muscle selective androgen receptor modulators through scaffold modifications. J Med Chem 2007;50:3015-25
  • Higuchi RI, Arienti KL, López FJ, et al. Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. J Med Chem 2007;50:2486-96
  • Miner JN, Chang W, Chapman MS, et al. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology 2007;148:363-73
  • Ryall JG, Lynch GS. The potential and the pitfalls of β-adrenoceptor agonists for the management of skeletal muscle wasting. Pharm Ther 2008; In press
  • Ryall JG, Schertzer JD, Lynch GS. Attenuation of age-related muscle wasting and weakness in rats after formoterol treatment: therapeutic implications for sarcopenia. J Gerontol A Biol Sci Med Sci 2007;62:813-23
  • Ryall JG, Sillence MN, Lynch GS. Systemic administration of β2-adrenoceptor agonists, formoterol and salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses. Br J Pharmacol 2006;147:587-95
  • Bauer JM, Sieber CC. Sarcopenia and frailty: a clinician's controversial point of view. Exp Gerontol 2008;43:674-8
  • Simm A, Rando TA. Tissue ageing: do insights into molecular mechanisms of ageing lead to new therapeutic strategies? Exp Gerontol 2008;43:603-4

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.