Current and future pharmacologic treatment of sarcopenia

Clinics in Geriatric Medicine

Volumn 27, Issue 3, 2011, Pages 423-447

  Rolland, Yves ^a,b   Onder, Graziano ^c   Morley, John E ^d,e   Gillette Guyonet, Sophie ^a,b   Abellan van Kan, Gabor ^a,b   Vellas, Bruno ^a,b  

^a INSERM   (France)

^b CHU PURPAN   (France)

^c CATHOLIC UNIVERSITY   (Italy)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

^e SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

ACE; Creatine; Growth hormone; Leptin; Myostatin; Sarcopenia; Testosterone; Vitamin D

Indexed keywords

25,26 DIHYDROXYCOLECALCIFEROL; ANTIINFLAMMATORY AGENT; ANTIMETABOLITE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BICARBONATE; CREATININE; CYTOKINE INHIBITOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ESTROGEN; GHRELIN; GINKGO BILOBA EXTRACT; GROWTH HORMONE; GROWTH HORMONE SECRETAGOGUE; GROWTH INHIBITOR; HORMONE RECEPTOR BLOCKING AGENT; HUMAN GROWTH HORMONE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LEPTIN; MELANOCORTIN 4 RECEPTOR ANTAGONIST; MYOSTATIN INHIBITOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; PLACEBO; POLYUNSATURATED FATTY ACID; PROTEIN INHIBITOR; SELECTIVE ANDROGEN RECEPTOR MODULATOR; TESTOSTERONE; TIBOLONE; UBIQUINONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASODILATOR AGENT; VITAMIN D;

AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTHRALGIA; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BODY COMPOSITION; BODY MASS; BRADYCARDIA; BREAST CANCER; CACHEXIA; CALORIC INTAKE; CARDIOVASCULAR DISEASE; CARPAL TUNNEL SYNDROME; DIABETES MELLITUS; DISEASE ASSOCIATION; DRUG EFFECT; DRUG TOLERABILITY; DRUG WITHDRAWAL; EDEMA; EXERCISE; FALLING; FATIGUE; FLUID RETENTION; FOOT EDEMA; GLUCOSE BLOOD LEVEL; GRIP STRENGTH; GYNECOMASTIA; HEMATOCRIT; HORMONE SUBSTITUTION; HUMAN; HYPERKALEMIA; IMMUNE DEFICIENCY; INCREASED APPETITE; INSOMNIA; INSULIN RESISTANCE; LEAN BODY WEIGHT; MUSCLE ATROPHY; MUSCLE FUNCTION; MUSCLE GROWTH; MUSCLE MASS; MUSCLE STRENGTH; MYALGIA; MYOTOXICITY; NONHUMAN; ORTHOSTATIC HYPOTENSION; PHYSICAL PERFORMANCE; PROTEIN INTAKE; REVIEW; RISK BENEFIT ANALYSIS; SENESCENCE; SIDE EFFECT; SOFT TISSUE DISEASE; STROKE; SUPPLEMENTATION; TOXICITY; VENOUS THROMBOEMBOLISM; VITAMIN D INTOXICATION; WEIGHT GAIN;

AGED; AGING; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; DRUG THERAPY; FRAIL ELDERLY; HORMONES; HUMANS; MUSCLE WEAKNESS; SARCOPENIA;

EID: 79961046708     PISSN: 07490690     EISSN: 18798853     Source Type: Journal    
DOI: 10.1016/j.cger.2011.03.008     Document Type: Review

References (194)

1. Morley J.E., Argiles J.M., Evans W.J., et al. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc 2009, 11(6):391-396.
2. Morley J.E., Kaiser F.E., Perry H.M., et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism 1997, 46(4):410-413.
3. Baumgartner R.N., Waters D.L., Gallagher D., et al. Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev 1999, 107(2):123-136.
4. Perry H.M., Miller D.K., Patrick P., et al. Testosterone and leptin in older African-American men: relationship to age, strength, function, and season. Metabolism 2000, 49(8):1085-1091.
5. Galvao D.A., Spry N.A., Taaffe D.R., et al. Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer. BJU Int 2008, 102(1):44-47.
6. Rolland Y., Czerwinski S., Abellan Van Kan G., et al. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging 2008, 12(7):433-450.
7. Tenover J.S. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 1992, 75(4):1092-1098.
8. Morley J.E., Perry H.M., Kaiser F.E., et al. Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J Am Geriatr Soc 1993, 41(2):149-152.
9. Katznelson L., Finkelstein J.S., Schoenfeld D.A., et al. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996, 81(12):4358-4365.
10. Sih R., Morley J.E., Kaiser F.E., et al. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 1997, 82(6):1661-1667.
11. Ly L.P., Jimenez M., Zhuang T.N., et al. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab 2001, 86(9):4078-4088.
12. Kenny A.M., Prestwood K.M., Gruman C.A., et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 2001, 56(5):M266-M272.
13. Wittert G.A., Chapman I.M., Haren M.T., et al. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci 2003, 58(7):618-625.
14. Emmelot-Vonk M.H., Verhaar H.J., Nakhai Pour H.R., et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 2008, 299(1):39-52.
15. Onder G., Della Vedova C., Landi F. Validated treatments and therapeutics prospectives regarding pharmacological products for sarcopenia. J Nutr Health Aging 2009, 13(8):746-756.
16. Ottenbacher K.J., Ottenbacher M.E., Ottenbacher A.J., et al. Androgen treatment and muscle strength in elderly men: a meta-analysis. J Am Geriatr Soc 2006, 54(11):1666-1673.
17. Srinivas-Shankar U., Roberts S.A., Connolly M.J., et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2010, 95(2):639-650.
18. Chapman I.M., Visvanathan R., Hammond A.J., et al. Effect of testosterone and a nutritional supplement, alone and in combination, on hospital admissions in undernourished older men and women. Am J Clin Nutr 2009, 89(3):880-889.
19. Kenny A.M., Boxer R.S., Kleppinger A., et al. Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women. J Am Geriatr Soc 2010, 58(9):1707-1714.
20. Basaria S., Coviello A.D., Travison T.G., et al. Adverse events associated with testosterone administration. N Engl J Med 2010, 363(2):109-122.
21. Wang C., Nieschlag E., Swerdloff R., et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl 2009, 30(1):1-9.
22. Bhasin S., Cunningham G.R., Hayes F.J., et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006, 91(6):1995-2010.
23. Bain J. Testosterone and the aging male: to treat or not to treat?. Maturitas 2010, 66(1):16-22.
24. Li J.J., Sutton J.C., Nirschl A., et al. Discovery of potent and muscle selective androgen receptor modulators through scaffold modifications. J Med Chem 2007, 50(13):3015-3025.
25. Morley J.E. Developing novel therapeutic approaches to frailty. Curr Pharm Des 2009, 15(29):3384-3395.
26. Gao W., Dalton J.T. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). Drug Discov Today 2007, 12(5-6):241-248.
27. Rudman D., Kutner M.H., Rogers C.M., et al. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest 1981, 67(5):1361-1369.
28. Taaffe D.R., Pruitt L., Reim J., et al. Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. J Clin Endocrinol Metab 1994, 79(5):1361-1366.
29. Yarasheski K.E., Zachwieja J.J., Campbell J.A., et al. Effect of growth hormone and resistance exercise on muscle growth and strength in older men. Am J Physiol 1995, 268(2 Pt 1):E268-E276.
30. Lange K.H., Andersen J.L., Beyer N., et al. GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men. J Clin Endocrinol Metab 2002, 87(2):513-523.
31. Hennessey J.V., Chromiak J.A., DellaVentura S., et al. Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people. J Am Geriatr Soc 2001, 49(7):852-858.
32. Thompson J.L., Butterfield G.E., Gylfadottir U.K., et al. Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women. J Clin Endocrinol Metab 1998, 83(5):1477-1484.
33. Hammarqvist F., Wennstrom I., Wernerman J. Effects of growth hormone and insulin-like growth factor-1 on postoperative muscle and substrate metabolism. J Nutr Metab 2010, 2010. pii: 647929.
34. Welle S., Thornton C., Statt M., et al. Growth hormone increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old. J Clin Endocrinol Metab 1996, 81(9):3239-3243.
35. Sugimoto T., Nakaoka D., Nasu M., et al. Effect of recombinant human growth hormone in elderly osteoporotic women. Clin Endocrinol (Oxf) 1999, 51(6):715-724.
36. Sattler F.R., Castaneda-Sceppa C., Binder E.F., et al. Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab 2009, 94(6):1991-2001.
37. Blackman M.R., Sorkin J.D., Munzer T., et al. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA 2002, 288(18):2282-2292.
38. Brill K.T., Weltman A.L., Gentili A., et al. Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men. J Clin Endocrinol Metab 2002, 87(12):5649-5657.
39. Nagaya N., Uematsu M., Kojima M., et al. Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 2001, 104(12):1430-1435.
40. Molfino A., Laviano A., Rossi Fanelli F. Contribution of anorexia to tissue wasting in cachexia. Curr Opin Support Palliat Care 2010, 4(4):249-253.
41. Kung T., Springer J., Doehner W., et al. Novel treatment approaches to cachexia and sarcopenia: highlights from the 5th Cachexia Conference. Expert Opin Investig Drugs 2010, 19(4):579-585.
42. Tai K., Visvanathan R., Hammond A.J., et al. Fasting ghrelin is related to skeletal muscle mass in healthy adults. Eur J Nutr 2009, 48(3):176-183.
43. Nass R., Pezzoli S.S., Oliveri M.C., et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med 2008, 149(9):601-611.
44. Garcia J.M., Polvino W.J. Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers. Oncologist 2007, 12(5):594-600.
45. White H.K., Petrie C.D., Landschulz W., et al. Effects of an oral growth hormone secretagogue in older adults. J Clin Endocrinol Metab 2009, 94(4):1198-1206.
46. Farooqi I.S., Keogh J.M., Yeo G.S., et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003, 348(12):1085-1095.
47. Scarlett J.M., Bowe D.D., Zhu X., et al. Genetic and pharmacologic blockade of central melanocortin signaling attenuates cardiac cachexia in rodent models of heart failure. J Endocrinol 2010, 206(1):121-130.
48. von Haehling S., Stepney R., Anker S.D. Advances in understanding and treating cardiac cachexia: highlights from the 5th Cachexia Conference. Int J Cardiol 2010, 144(3):347-349.
49. Gallagher D., Visser M., De Meersman R.E., et al. Appendicular skeletal muscle mass: effects of age, gender, and ethnicity. J Appl Physiol 1997, 83(1):229-239.
50. Maltais M.L., Desroches J., Dionne I.J. Changes in muscle mass and strength after menopause. J Musculoskelet Neuronal Interact 2009, 9(4):186-197.
51. Jacobsen D.E., Samson M.M., Kezic S., et al. Postmenopausal HRT and tibolone in relation to muscle strength and body composition. Maturitas 2007, 58(1):7-18.
52. Chlebowski R.T., Schwartz A.G., Wakelee H., et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet 2009, 374(9697):1243-1251.
53. Meeuwsen I.B., Samson M.M., Duursma S.A., et al. Muscle strength and tibolone: a randomised, double-blind, placebo-controlled trial. BJOG 2002, 109(1):77-84.
54. Meeuwsen I.B., Samson M.M., Duursma S.A., et al. The effect of tibolone on fat mass, fat-free mass, and total body water in postmenopausal women. Endocrinology 2001, 142(11):4813-4817.
55. Arabi A., Garnero P., Porcher R., et al. Changes in body composition during post-menopausal hormone therapy: a 2 year prospective study. Hum Reprod 2003, 18(8):1747-1752.
56. Hanggi W., Lippuner K., Jaeger P., et al. Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women. Clin Endocrinol (Oxf) 1998, 48(6):691-699.
57. Tommaselli G.A., Di Carlo C., Di Spiezio Sardo A., et al. Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene. Menopause 2006, 13(4):660-668.
58. Boyanov M.A., Shinkov A.D. Effects of tibolone on body composition in postmenopausal women: a 1-year follow up study. Maturitas 2005, 51(4):363-369.
59. Welton A.J., Vickers M.R., Kim J., et al. Health related quality of life after combined hormone replacement therapy: randomised controlled trial. BMJ 2008, 337:a1190.
60. Lemoine S., Granier P., Tiffoche C., et al. Estrogen receptor alpha mRNA in human skeletal muscles. Med Sci Sports Exerc 2003, 35(3):439-443.
61. Wiik A., Ekman M., Morgan G., et al. Oestrogen receptor beta is present in both muscle fibres and endothelial cells within human skeletal muscle tissue. Histochem Cell Biol 2005, 124(2):161-165.
62. Dieli-Conwright C.M., Spektor T.M., Rice J.C., et al. Influence of hormone replacement therapy on eccentric exercise induced myogenic gene expression in postmenopausal women. J Appl Physiol 2009, 107(5):1381-1388.
63. Dieli-Conwright C.M., Spektor T.M., Rice J.C., et al. Hormone therapy attenuates exercise-induced skeletal muscle damage in postmenopausal women. J Appl Physiol 2009, 107(3):853-858.
64. Huffman K.M., Slentz C.A., Johnson J.L., et al. Impact of hormone replacement therapy on exercise training-induced improvements in insulin action in sedentary overweight adults. Metabolism 2008, 57(7):888-895.
65. Sahu A. Minireview: a hypothalamic role in energy balance with special emphasis on leptin. Endocrinology 2004, 145(6):2613-2620.
66. Ceddia R.B., William W.N., Curi R. The response of skeletal muscle to leptin. Front Biosci 2001, 6:D90-D97.
67. Trostler N., Romsos D.R., Bergen W.G., et al. Skeletal muscle accretion and turnover in lean and obese (ob/ob) mice. Metabolism 1979, 28(9):928-933.
68. Sainz N., Rodriguez A., Catalan V., et al. Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS One 2009, 4(9):e6808.
69. Banks W.A., Coon A.B., Robinson S.M., et al. Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 2004, 53(5):1253-1260.
70. Holick M.F. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med 2008, 29(6):361-368.
71. Morley J.E. Vitamin d redux. J Am Med Dir Assoc 2009, 10(9):591-592.
72. Braddy K.K., Imam S.N., Palla K.R., et al. Vitamin d deficiency/insufficiency practice patterns in a veterans health administration long-term care population: a retrospective analysis. J Am Med Dir Assoc 2009, 10(9):653-657.
73. Visser M., Deeg D.J., Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 2003, 88(12):5766-5772.
74. Bischoff H.A., Stahelin H.B., Dick W., et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003, 18(2):343-351.
75. Pfeifer M., Begerow B., Minne H.W., et al. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int 2009, 20(2):315-322.
76. Moreira-Pfrimer L.D., Pedrosa M.A., Teixeira L., et al. Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: a randomized double-blind controlled trial. Ann Nutr Metab 2009, 54(4):291-300.
77. Pfeifer M., Begerow B., Minne H.W., et al. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000, 15(6):1113-1118.
78. Bischoff-Ferrari H.A., Orav E.J., Dawson-Hughes B. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Arch Intern Med 2006, 166(4):424-430.
79. Bischoff-Ferrari H.A., Dawson-Hughes B., Staehelin H.B., et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 2009, 339:b3692.
80. Boland R. Role of vitamin D in skeletal muscle function. Endocr Rev 1986, 7(4):434-448.
81. Wassner S.J., Li J.B., Sperduto A., et al. Vitamin D Deficiency, hypocalcemia, and increased skeletal muscle degradation in rats. J Clin Invest 1983, 72(1):102-112.
82. Janssen H.C., Samson M.M., Verhaar H.J. Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr 2002, 75(4):611-615.
83. Sorensen O.H., Lund B., Saltin B., et al. Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. Clin Sci (Lond) 1979, 56(2):157-161.
84. Ceglia L. Vitamin D and its role in skeletal muscle. Curr Opin Clin Nutr Metab Care 2009, 12(6):628-633.
85. Bischoff H.A., Borchers M., Gudat F., et al. In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J 2001, 33(1):19-24.
86. Roth S.M., Zmuda J.M., Cauley J.A., et al. Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men. J Gerontol A Biol Sci Med Sci 2004, 59(1):10-15.
87. Hamilton B. Vitamin D and human skeletal muscle. Scand J Med Sci Sports 2010, 20(2):182-190.
88. Nguyen T.M., Lieberherr M., Fritsch J., et al. The rapid effects of 1,25-dihydroxyvitamin D3 require the vitamin D receptor and influence 24-hydroxylase activity: studies in human skin fibroblasts bearing vitamin D receptor mutations. J Biol Chem 2004, 279(9):7591-7597.
89. Artaza J.N., Bhasin S., Magee T.R., et al. Myostatin inhibits myogenesis and promotes adipogenesis in C3H 10T(1/2) mesenchymal multipotent cells. Endocrinology 2005, 146(8):3547-3557.
90. Amirouche A., Durieux A.C., Banzet S., et al. Down-regulation of Akt/mammalian target of rapamycin signaling pathway in response to myostatin overexpression in skeletal muscle. Endocrinology 2009, 150(1):286-294.
91. Schuelke M., Wagner K.R., Stolz L.E., et al. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 2004, 350(26):2682-2688.
92. Siriett V., Salerno M.S., Berry C., et al. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Mol Ther 2007, 15(8):1463-1470.
93. Haidet A.M., Rizo L., Handy C., et al. Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Proc Natl Acad Sci U S A 2008, 105(11):4318-4322.
94. Rodino-Klapac L.R., Haidet A.M., Kota J., et al. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve 2009, 39(3):283-296.
95. Tsuchida K. Targeting myostatin for therapies against muscle-wasting disorders. Curr Opin Drug Discov Devel 2008, 11(4):487-494.
96. Solomon A.M., Bouloux P.M. Modifying muscle mass - the endocrine perspective. J Endocrinol 2006, 191(2):349-360.
97. Nakatani M., Takehara Y., Sugino H., et al. Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice. FASEB J 2008, 22(2):477-487.
98. Ohsawa Y., Hagiwara H., Nakatani M., et al. Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition. J Clin Invest 2006, 116(11):2924-2934.
99. Minetti G.C., Colussi C., Adami R., et al. Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Nat Med 2006, 12(10):1147-1150.
100. Gilson H., Schakman O., Kalista S., et al. Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin. Am J Physiol Endocrinol Metab 2009, 297(1):E157-E164.
101. Mendias C.L., Bakhurin K.I., Faulkner J.A. Tendons of myostatin-deficient mice are small, brittle, and hypocellular. Proc Natl Acad Sci U S A 2008, 105(1):388-393.
102. Savo A., Maiorano P.M., Onder G., et al. Pharmacoepidemiology and disability in older adults: can medications slow the age-related decline in physical function?. Expert Opin Pharmacother 2004, 5(2):407-413.
103. Jones A., Woods D.R. Skeletal muscle RAS and exercise performance. Int J Biochem Cell Biol 2003, 35(6):855-866.
104. Onder G., Vedova C.D., Pahor M. Effects of ACE inhibitors on skeletal muscle. Curr Pharm Des 2006, 12(16):2057-2064.
105. Sumukadas D., Witham M.D., Struthers A.D., et al. Ace inhibitors as a therapy for sarcopenia - evidence and possible mechanisms. J Nutr Health Aging 2008, 12(7):480-485.
106. Onder G., Penninx B.W., Balkrishnan R., et al. Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet 2002, 359(9310):926-930.
107. Di Bari M., van de Poll-Franse L.V., Onder G., et al. Antihypertensive medications and differences in muscle mass in older persons: the health, aging and body composition study. J Am Geriatr Soc 2004, 52(6):961-966.
108. Cesari M., Pedone C., Incalzi R.A., et al. ACE-inhibition and physical function: results from the Trial of Angiotensin-Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study. J Am Med Dir Assoc 2010, 11(1):26-32.
109. Bunout D., Barrera G., de la Maza M.P., et al. Effects of enalapril or nifedipine on muscle strength or functional capacity in elderly subjects. A double blind trial. J Renin Angiotensin Aldosterone Syst 2009, 10(2):77-84.
110. Sumukadas D., Witham M.D., Struthers A.D., et al. Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial. CMAJ 2007, 177(8):867-874.
111. Danser A.H., Schalekamp M.A., Bax W.A., et al. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 1995, 92(6):1387-1388.
112. Frederiksen H., Gaist D., Bathum L., et al. Angiotensin I-converting enzyme (ACE) gene polymorphism in relation to physical performance, cognition and survival-a follow-up study of elderly Danish twins. Ann Epidemiol 2003, 13(1):57-65.
113. Kritchevsky S.B., Nicklas B.J., Visser M., et al. Angiotensin-converting enzyme insertion/deletion genotype, exercise, and physical decline. JAMA 2005, 294(6):691-698.
114. Zhang B., Tanaka H., Shono N., et al. The I allele of the angiotensin-converting enzyme gene is associated with an increased percentage of slow-twitch type I fibers in human skeletal muscle. Clin Genet 2003, 63(2):139-144.
115. Montgomery H.E., Marshall R., Hemingway H., et al. Human gene for physical performance. Nature 1998, 393(6682):221-222.
116. Williams A.G., Rayson M.P., Jubb M., et al. The ACE gene and muscle performance. Nature 2000, 403(6770):614.
117. Montgomery H., Clarkson P., Barnard M., et al. Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training. Lancet 1999, 353(9152):541-545.
118. Vigano A., Trutschnigg B., Kilgour R.D., et al. Relationship between angiotensin-converting enzyme gene polymorphism and body composition, functional performance, and blood biomarkers in advanced cancer patients. Clin Cancer Res 2009, 15(7):2442-2447.
119. Habouzit E., Richard H., Sanchez H., et al. Decreased muscle ACE activity enhances functional response to endurance training in rats, without change in muscle oxidative capacity or contractile phenotype. J Appl Physiol 2009, 107(1):346-353.
120. Rizzoni D., Pasini E., Flati V., et al. Angiotensin receptor blockers improve insulin signaling and prevent microvascular rarefaction in the skeletal muscle of spontaneously hypertensive rats. J Hypertens 2008, 26(8):1595-1601.
121. Guo Q., Minami N., Mori N., et al. Effects of estradiol, angiotensin-converting enzyme inhibitor and exercise training on exercise capacity and skeletal muscle in old female rats. Clin Exp Hypertens 2010, 32(2):76-83.
122. Takeshita S., Tomiyama H., Yokoyama N., et al. Angiotensin-converting enzyme inhibition improves defective angiogenesis in the ischemic limb of spontaneously hypertensive rats. Cardiovasc Res 2001, 52(2):314-320.
123. Weisinger R.S., Stanley T.K., Begg D.P., et al. Angiotensin converting enzyme inhibition lowers body weight and improves glucose tolerance in C57BL/6J mice maintained on a high fat diet. Physiol Behav 2009, 98(1-2):192-197.
124. Clerk L.H., Vincent M.A., Barrett E.J., et al. Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiotensin-converting enzyme inhibition. Am J Physiol Endocrinol Metab 2007, 293(6):E1804-E1809.
125. Han Y., Runge M.S., Brasier A.R. Angiotensin II induces interleukin-6 transcription in vascular smooth muscle cells through pleiotropic activation of nuclear factor-kappa B transcription factors. Circ Res 1999, 84(6):695-703.
126. Kranzhofer R., Schmidt J., Pfeiffer C.A., et al. Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1999, 19(7):1623-1629.
127. Browatzki M., Larsen D., Pfeiffer C.A., et al. Angiotensin II stimulates matrix metalloproteinase secretion in human vascular smooth muscle cells via nuclear factor-kappaB and activator protein 1 in a redox-sensitive manner. J Vasc Res 2005, 42(5):415-423.
128. Payne G.W. Effect of inflammation on the aging microcirculation: impact on skeletal muscle blood flow control. Microcirculation 2006, 13(4):343-352.
129. Brull D.J., Sanders J., Rumley A., et al. Impact of angiotensin converting enzyme inhibition on post-coronary artery bypass interleukin 6 release. Heart 2002, 87(3):252-255.
130. Tian Q., Miyazaki R., Ichiki T., et al. Inhibition of tumor necrosis factor-alpha-induced interleukin-6 expression by telmisartan through cross-talk of peroxisome proliferator-activated receptor-gamma with nuclear factor kappaB and CCAAT/enhancer-binding protein-beta. Hypertension 2009, 53(5):798-804.
131. Fujita K., Yoneda M., Wada K., et al. Telmisartan, an angiotensin II type 1 receptor blocker, controls progress of nonalcoholic steatohepatitis in rats. Dig Dis Sci 2007, 52(12):3455-3464.
132. Sugimoto K., Kazdova L., Qi N.R., et al. Telmisartan increases fatty acid oxidation in skeletal muscle through a peroxisome proliferator-activated receptor-gamma dependent pathway. J Hypertens 2008, 26(6):1209-1215.
133. Giovannini S., Marzetti E., Borst S.E., et al. Modulation of GH/IGF-1 axis: potential strategies to counteract sarcopenia in older adults. Mech Ageing Dev 2008, 129(10):593-601.
134. Musaro A., McCullagh K.J., Naya F.J., et al. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. Nature 1999, 400(6744):581-585.
135. Brink M., Price S.R., Chrast J., et al. Angiotensin II induces skeletal muscle wasting through enhanced protein degradation and down-regulates autocrine insulin-like growth factor I. Endocrinology 2001, 142(4):1489-1496.
136. Onder G., Liperoti R., Russo A., et al. Use of ACE inhibitors is associated with elevated levels of IGFBP-3 among hypertensive older adults: results from the IlSIRENTE study. Eur J Clin Pharmacol 2007, 63(4):389-395.
137. Maggio M., Ceda G.P., Lauretani F., et al. Relation of angiotensin-converting enzyme inhibitor treatment to insulin-like growth factor-1 serum levels in subjects >65 years of age (the InCHIANTI study). Am J Cardiol 2006, 97(10):1525-1529.
138. Armitage J., Bowman L., Collins R., et al. Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebo-controlled trial in 20,536 high-risk people. BMC Clin Pharmacol 2009, 9:6.
139. Robinson M.M., Hamilton K.L., Miller B.F. The interactions of some commonly consumed drugs with mitochondrial adaptations to exercise. J Appl Physiol 2009, 107(1):8-16.
140. Scott D., Blizzard L., Fell J., et al. Statin therapy, muscle function and falls risk in community-dwelling older adults. QJM 2009, 102(9):625-633.
141. Giri J., McDermott M.M., Greenland P., et al. Statin use and functional decline in patients with and without peripheral arterial disease. J Am Coll Cardiol 2006, 47(5):998-1004.
142. Agostini J.V., Tinetti M.E., Han L., et al. Effects of statin use on muscle strength, cognition, and depressive symptoms in older adults. J Am Geriatr Soc 2007, 55(3):420-425.
143. LaCroix A.Z., Gray S.L., Aragaki A., et al. Statin use and incident frailty in women aged 65 years or older: prospective findings from the Women's Health Initiative Observational Study. J Gerontol A Biol Sci Med Sci 2008, 63(4):369-375.
144. Riechman S.E., Andrews R.D., Maclean D.A., et al. Statins and dietary and serum cholesterol are associated with increased lean mass following resistance training. J Gerontol A Biol Sci Med Sci 2007, 62(10):1164-1171.
145. Clough G.F., Turzyniecka M., Walter L., et al. Muscle microvascular dysfunction in central obesity is related to muscle insulin insensitivity but is not reversed by high-dose statin treatment. Diabetes 2009, 58(5):1185-1191.
146. Thompson P.D., Parker B.A., Clarkson P.M., et al. A randomized clinical trial to assess the effect of statins on skeletal muscle function and performance: rationale and study design. Prev Cardiol 2010, 13(3):104-111.
147. Ades P.A., Gunther P.G., Meyer W.L., et al. Cardiac and skeletal muscle adaptations to training in systemic hypertension and effect of beta blockade (metoprolol or propranolol). Am J Cardiol 1990, 66(5):591-596.
148. Langin D. Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacol Res 2006, 53(6):482-491.
149. Dalla Libera L., Ravara B., Gobbo V., et al. Skeletal muscle proteins oxidation in chronic right heart failure in rats: can different beta-blockers prevent it to the same degree?. Int J Cardiol 2010, 143(2):192-199.
150. Scherrer U., Randin D., Vollenweider P., et al. Nitric oxide release accounts for insulin's vascular effects in humans. J Clin Invest 1994, 94(6):2511-2515.
151. Steinberg H.O., Brechtel G., Johnson A., et al. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994, 94(3):1172-1179.
152. Timmerman K.L., Lee J.L., Fujita S., et al. Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults. Diabetes 2010, 59(11):2764-2771.
153. Meneilly G.S., Elliot T., Bryer-Ash M., et al. Insulin-mediated increase in blood flow is impaired in the elderly. J Clin Endocrinol Metab 1995, 80(6):1899-1903.
154. Rasmussen B.B., Fujita S., Wolfe R.R., et al. Insulin resistance of muscle protein metabolism in aging. FASEB J 2006, 20(6):768-769.
155. Sindler A.L., Delp M.D., Reyes R., et al. Effects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles. J Physiol 2009, 587(Pt 15):3885-3897.
156. Haslett P., Hempstead M., Seidman C., et al. The metabolic and immunologic effects of short-term thalidomide treatment of patients infected with the human immunodeficiency virus. AIDS Res Hum Retroviruses 1997, 13(12):1047-1054.
157. Steffen B.T., Lees S.J., Booth F.W. Anti-TNF treatment reduces rat skeletal muscle wasting in monocrotaline-induced cardiac cachexia. J Appl Physiol 2008, 105(6):1950-1958.
158. Calabrese L.H., Zein N., Vassilopoulos D. Safety of antitumour necrosis factor (anti-TNF) therapy in patients with chronic viral infections: hepatitis C, hepatitis B, and HIV infection. Ann Rheum Dis 2004, 63(Suppl 2):ii18-ii24.
159. Ruxton C.H., Reed S.C., Simpson M.J., et al. The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. J Hum Nutr Diet 2004, 17(5):449-459.
160. Stillwell W., Wassall S.R. Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids 2003, 126(1):1-27.
161. Haugaard S.B., Vaag A., Mu H., et al. Skeletal muscle structural lipids improve during weight-maintenance after a very low calorie dietary intervention. Lipids Health Dis 2009, 8:34.
162. Maillet D., Weber J.M. Relationship between n-3 PUFA content and energy metabolism in the flight muscles of a migrating shorebird: evidence for natural doping. J Exp Biol 2007, 210(Pt 3):413-420.
163. Barber M.D., Ross J.A., Voss A.C., et al. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer 1999, 81(1):80-86.
164. Broekhuizen R., Wouters E.F., Creutzberg E.C., et al. Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax 2005, 60(5):376-382.
165. Robinson S.M., Jameson K.A., Batelaan S.F., et al. Diet and its relationship with grip strength in community-dwelling older men and women: the Hertfordshire cohort study. J Am Geriatr Soc 2008, 56(1):84-90.
166. Rousseau J.H., Kleppinger A., Kenny A.M. Self-reported dietary intake of omega-3 fatty acids and association with bone and lower extremity function. J Am Geriatr Soc 2009, 57(10):1781-1788.
167. Calder P.C. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006, 83(Suppl 6):1505S-1519S.
168. Smith G.I., Atherton P., Reeds D.N., et al. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr 2011, 93(2):402-412.
169. 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(4):1560-1569.
170. Trappe T.A., Carroll C.C., Dickinson J.M., et al. Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. Am J Physiol Regul Integr Comp Physiol 2011, 300(3):R655-R662.
171. Brose A., Parise G., Tarnopolsky M.A. Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J Gerontol A Biol Sci Med Sci 2003, 58(1):11-19.
172. Jones A.M., Wilkerson D.P., Fulford J. Influence of dietary creatine supplementation on muscle phosphocreatine kinetics during knee-extensor exercise in humans. Am J Physiol Regul Integr Comp Physiol 2009, 296(4):R1078-R1087.
173. Chrusch M.J., Chilibeck P.D., Chad K.E., et al. Creatine supplementation combined with resistance training in older men. Med Sci Sports Exerc 2001, 33(12):2111-2117.
174. Rawson E.S., Wehnert M.L., Clarkson P.M. Effects of 30 days of creatine ingestion in older men. Eur J Appl Physiol Occup Physiol 1999, 80(2):139-144.
175. Bermon S., Venembre P., Sachet C., et al. Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults. Acta Physiol Scand 1998, 164(2):147-155.
176. Jakobi J.M., Rice C.L., Curtin S.V., et al. Neuromuscular properties and fatigue in older men following acute creatine supplementation. Eur J Appl Physiol 2001, 84(4):321-328.
177. Rawson E.S., Clarkson P.M. Acute creatine supplementation in older men. Int J Sports Med 2000, 21(1):71-75.
178. Stout J.R., Sue Graves B., Cramer J.T., et al. Effects of creatine supplementation on the onset of neuromuscular fatigue threshold and muscle strength in elderly men and women (64-86 years). J Nutr Health Aging 2007, 11(6):459-464.
179. Tarnopolsky M., Zimmer A., Paikin J., et al. Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults. PLoS One 2007, 2(10):e991.
180. Burke D.G., Chilibeck P.D., Parise G., et al. Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med Sci Sports Exerc 2003, 35(11):1946-1955.
181. Candow D.G., Little J.P., Chilibeck P.D., et al. Low-dose creatine combined with protein during resistance training in older men. Med Sci Sports Exerc 2008, 40(9):1645-1652.
182. Willoughby D.S., Rosene J.M. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc 2003, 35(6):923-929.
183. Parise G., Mihic S., MacLennan D., et al. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol 2001, 91(3):1041-1047.
184. Sestili P., Martinelli C., Bravi G., et al. Creatine supplementation affords cytoprotection in oxidatively injured cultured mammalian cells via direct antioxidant activity. Free Radic Biol Med 2006, 40(5):837-849.
185. Balsom P.D., Soderlund K., Sjodin B., et al. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand 1995, 154(3):303-310.
186. Francaux M., Poortmans J.R. Effects of training and creatine supplement on muscle strength and body mass. Eur J Appl Physiol Occup Physiol 1999, 80(2):165-168.
187. Olsen S., Aagaard P., Kadi F., et al. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J Physiol 2006, 573(Pt 2):525-534.
188. Dawson-Hughes B., Castaneda-Sceppa C., Harris S.S., et al. Impact of supplementation with bicarbonate on lower-extremity muscle performance in older men and women. Osteoporos Int 2010, 21(7):1171-1179.
189. Cao Z., Wu Y., Curry K., et al. Ginkgo biloba extract EGb 761 and Wisconsin Ginseng delay sarcopenia in Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci 2007, 62(12):1337-1345.
190. Bidon C., Lachuer J., Molgo J., et al. The extract of Ginkgo biloba EGb 761 reactivates a juvenile profile in the skeletal muscle of sarcopenic rats by transcriptional reprogramming. PLoS One 2009, 4(11):e7998.
191. Xu J., Seo A.Y., Vorobyeva D.A., et al. Beneficial effects of a Q-ter based nutritional mixture on functional performance, mitochondrial function, and oxidative stress in rats. PLoS One 2010, 5(5):e10572.
192. Sumien N., Heinrich K.R., Shetty R.A., et al. Prolonged intake of coenzyme Q10 impairs cognitive functions in mice. J Nutr 2009, 139(10):1926-1932.
193. Abellan van Kan G., Rolland Y.M., Morley J.E., et al. Frailty: toward a clinical definition. J Am Med Dir Assoc 2008, 9(2):71-72.
194. Morley J.E., Kim M.J., Haren M.T., et al. Frailty and the aging male. Aging Male 2005, 8(3-4):135-140.