Amino Acids

, Volume 45, Issue 3, pp 431–441 | Cite as

Nutritionally essential amino acids and metabolic signaling in aging

Review Article

Abstract

Aging is associated with a gradual decline in skeletal muscle mass and strength leading to increased risk for functional impairments. Although basal rates of protein synthesis and degradation are largely unaffected with age, the sensitivity of older muscle cells to the anabolic actions of essential amino acids appears to decline. The major pathway through which essential amino acids induce anabolic responses involves the mammalian target of rapamycin (mTOR) Complex 1, a signaling pathway that is especially sensitive to regulation by the branched chain amino acid leucine. Recent evidence suggests that muscle of older individuals require increasing concentrations of leucine to maintain robust anabolic responses through the mTOR pathway. While the exact mechanisms for the age-related alterations in nutritional signaling through the mTOR pathway remain elusive, there is increasing evidence that decreased sensitivity to insulin action, reductions in endothelial function, and increased oxidative stress may be underlying factors in this decrease in anabolic sensitivity. Ensuring adequate nutrition, including sources of high quality protein, and promoting regular physical activity will remain among the frontline defenses against the onset of sarcopenia in older individuals.

Keywords

Skeletal muscle Protein synthesis Anabolic resistance 

Abbreviations

AA

Amino acid

Akt/PKB

Protein kinase B

BCAA

Branched chain AA

EAA

Essential AA

4E-BP1

eIF4E Binding protein

eEf

Eukaryotic elongation factor

eIF

Eukaryotic initiation factor

FSR

Fractional synthetic rate

GβL

G-protein-β-subunit-like protein

GDP

Guanosine diphosphate

GTP

Guanosine triphosphate

hVps34

Human vacuolar protein sorting 34

IGF-1

Insulin-like growth factor 1

LRS

Leucyl-tRNA synthetase

mTOR

Mammalian target of rapamycin

NEAA

Nonessential AA

NO

Nitric oxide

PI3K

Phosphatidylinositol 3-kinase

Rag

Ras-related GTPase

Raptor

Regulatory-associated protein of mTOR

Rheb

Ras homologue enhanced in brain

S6K1

p70 ribosomal protein S6 kinase 1

SNP

Sodium nitroprusside

TSC

Tuberous sclerosis complex

References

  1. Abbatecola AM, Paolisso G, Fattoretti P et al (2011) Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction. J Nutr Health Aging 15(10):890–895PubMedCrossRefGoogle Scholar
  2. Anthony JC, Lang CH, Crozier SJ et al (2002) Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. Am J Physiol Endocrinol Metab 282(5):E1092–E1101PubMedGoogle Scholar
  3. Atherton PJ, Smith K, Etheridge T et al (2009) Distinct anabolic signalling responses to amino acids in C2C12 skeletal muscle cells. Amino Acids 38(5):1533–1539PubMedCrossRefGoogle Scholar
  4. Balage M, Sinaud S, Prod’homme M et al (2001) Amino acids and insulin are both required to regulate assembly of the eIF4E. eIF4G complex in rat skeletal muscle. Am J Physiol Endocrinol Metab 281(3):E565–E574PubMedGoogle Scholar
  5. Baumgartner RN, Koehler KM, Gallagher D et al (1998) Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 147(8):755–763PubMedCrossRefGoogle Scholar
  6. Biolo G, Maggi SP, Williams BD et al (1995) Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Am J Physiol 268(3 Pt 1):E514–E520PubMedGoogle Scholar
  7. Biolo G, Williams BD, Fleming RY et al (1999) Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise. Diabetes 48(5):949–957PubMedCrossRefGoogle Scholar
  8. Boirie Y, Gachon P, Beaufrere B (1997) Splanchnic and whole-body leucine kinetics in young and elderly men. Am J Clin Nutr 65(2):489–495PubMedGoogle Scholar
  9. Borsheim E, Bui QU, Tissier S et al (2008) Effect of amino acid supplementation on muscle mass, strength and physical function in elderly. Clin Nutr 27(2):189–195PubMedCrossRefGoogle Scholar
  10. Breen L, Phillips SM (2011) Skeletal muscle protein metabolism in the elderly: interventions to counteract the ‘anabolic resistance’ of ageing. Nutr Metab (Lond) 8:68CrossRefGoogle Scholar
  11. Browne GJ, Proud CG (2004) A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin. Mol Cell Biol 24(7):2986–2997PubMedCrossRefGoogle Scholar
  12. Buse MG, Reid SS (1975) Leucine. A possible regulator of protein turnover in muscle. J Clin Invest 56(5):1250–1261PubMedCrossRefGoogle Scholar
  13. Byfield MP, Murray JT, Backer JM (2005) hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem 280(38):33076–33082PubMedCrossRefGoogle Scholar
  14. Campbell LE, Wang X, Proud CG (1999) Nutrients differentially regulate multiple translation factors and their control by insulin. Biochem J 344(Pt 2):433–441PubMedCrossRefGoogle Scholar
  15. Casperson SL, Sheffield-Moore M, Hewlings SJ et al (2012) Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein. Clin Nutr 31(4):512–519PubMedCrossRefGoogle Scholar
  16. Chevalier S, Goulet ED, Burgos SA et al (2011) Protein anabolic responses to a fed steady state in healthy aging. J Gerontol A Biol Sci Med Sci 66(6):681–688PubMedCrossRefGoogle Scholar
  17. Coggins M, Lindner J, Rattigan S et al (2001) Physiologic hyperinsulinemia enhances human skeletal muscle perfusion by capillary recruitment. Diabetes 50(12):2682–2690PubMedCrossRefGoogle Scholar
  18. Crozier SJ, Kimball SR, Emmert SW et al (2005) Oral leucine administration stimulates protein synthesis in rat skeletal muscle. J Nutr 135(3):376–382PubMedGoogle Scholar
  19. Cruz-Jentoft AJ, Baeyens JP, Bauer JM et al (2010) Sarcopenia: european consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 39(4):412–423PubMedCrossRefGoogle Scholar
  20. Cuthbertson D, Smith K, Babraj J et al (2005) Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J 19(3):422–424PubMedGoogle Scholar
  21. Dardevet D, Sornet C, Balage M et al (2000) Stimulation of in vitro rat muscle protein synthesis by leucine decreases with age. J Nutr 130(11):2630–2635PubMedGoogle Scholar
  22. Deldicque L, Theisen D, Francaux M (2005) Regulation of mTOR by amino acids and resistance exercise in skeletal muscle. Eur J Appl Physiol 94(1–2):1–10PubMedCrossRefGoogle Scholar
  23. Dennis MD, Baum JI, Kimball SR et al (2011) Mechanisms involved in the coordinate regulation of mTORC1 by insulin and amino acids. J Biol Chem 286(10):8287–8296PubMedCrossRefGoogle Scholar
  24. Dillon EL, Sheffield-Moore M, Paddon-Jones D et al (2009) Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women. J Clin Endocrinol Metab 94(5):1630–1637PubMedCrossRefGoogle Scholar
  25. Dillon EL, Durham WJ, Urban RJ et al (2010) Hormone treatment and muscle anabolism during aging: androgens. Clin Nutr 29(6):697–700PubMedCrossRefGoogle Scholar
  26. Dillon EL, Casperson SL, Durham WJ et al (2011) Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia. Am J Physiol Regul Integr Comp Physiol 301(5):R1408–R1417PubMedCrossRefGoogle Scholar
  27. Dodd KM, Tee AR (2012) Leucine and mTORC1: a complex relationship. Am J Physiol Endocrinol Metab 302(11):E1329–E1342PubMedCrossRefGoogle Scholar
  28. Dreyer HC, Drummond MJ, Pennings B et al (2008) Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab 294(2):E392–E400PubMedCrossRefGoogle Scholar
  29. Dreyer HC, Fujita S, Glynn EL et al (2010) Resistance exercise increases leg muscle protein synthesis and mTOR signalling independent of sex. Acta Physiol (Oxf) 199(1):71–81CrossRefGoogle Scholar
  30. Drummond MJ, Dreyer HC, Pennings B et al (2008) Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. J Appl Physiol 104(5):1452–1461PubMedCrossRefGoogle Scholar
  31. Drummond MJ, Miyazaki M, Dreyer HC et al (2009) Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis. J Appl Physiol 106(4):1403–1411PubMedCrossRefGoogle Scholar
  32. Durham WJ, Casperson SL, Dillon EL et al (2010) Age-related anabolic resistance after endurance-type exercise in healthy humans. FASEB J 24(10):4117–4127PubMedCrossRefGoogle Scholar
  33. El-Kadi SW, Suryawan A, Gazzaneo MC et al (2012) Anabolic signaling and protein deposition are enhanced by intermittent compared with continuous feeding in skeletal muscle of neonates. Am J Physiol Endocrinol Metab 302(6):E674–E686PubMedCrossRefGoogle Scholar
  34. Ferrando AA, Sheffield-Moore M, Paddon-Jones D et al (2003) Differential anabolic effects of testosterone and amino acid feeding in older men. J Clin Endocrinol Metab 88(1):358–362PubMedCrossRefGoogle Scholar
  35. Ferrando AA, Paddon-Jones D, Hays NP et al (2009) EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr 29(1):18–23PubMedCrossRefGoogle Scholar
  36. Freudenberg A, Petzke KJ, Klaus S (2012) Comparison of high-protein diets and leucine supplementation in the prevention of metabolic syndrome and related disorders in mice. J Nutr Biochem 23(11):1524–1530PubMedCrossRefGoogle Scholar
  37. Fujita S, Rasmussen BB, Cadenas JG et al (2007) Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes 56(6):1615–1622PubMedCrossRefGoogle Scholar
  38. Gazzaneo MC, Suryawan A, Orellana RA et al (2011) Intermittent bolus feeding has a greater stimulatory effect on protein synthesis in skeletal muscle than continuous feeding in neonatal pigs. J Nutr 141(12):2152–2158PubMedCrossRefGoogle Scholar
  39. Glynn EL, Fry CS, Drummond MJ et al (2010) Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women. J Nutr 140(11):1970–1976PubMedCrossRefGoogle Scholar
  40. Gonzalez IM, Martin PM, Burdsal C et al (2011) Leucine and arginine regulate trophoblast motility through mTOR-dependent and independent pathways in the preimplantation mouse embryo. Dev Biol 361(2):286–300PubMedCrossRefGoogle Scholar
  41. Goodman CA, Frey JW, Mabrey DM et al (2011) The role of skeletal muscle mTOR in the regulation of mechanical load-induced growth. J Physiol 589(Pt 22):5485–5501PubMedGoogle Scholar
  42. Gran P, Cameron-Smith D (2011) The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes. BMC Physiol 11:10PubMedCrossRefGoogle Scholar
  43. Guillet C, Prod’homme M, Balage M et al (2004) Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J 18(13):1586–1587PubMedGoogle Scholar
  44. Haegens A, Schols AM, van Essen AL et al (2012) Leucine induces myofibrillar protein accretion in cultured skeletal muscle through mTOR dependent and -independent control of myosin heavy chain mRNA levels. Mol Nutr Food Res 56(5):741–752PubMedCrossRefGoogle Scholar
  45. Hafen E (2004) Interplay between growth factor and nutrient signaling: lessons from Drosophila TOR. Curr Top Microbiol Immunol 279:153–167PubMedCrossRefGoogle Scholar
  46. Han JM, Jeong SJ, Park MC et al (2012) Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149(2):410–424PubMedCrossRefGoogle Scholar
  47. Horstman AM, Dillon EL, Urban RJ et al (2012) The role of androgens and estrogens on healthy aging and longevity. J Gerontol A Biol Sci Med Sci 67(11):1140–1152PubMedCrossRefGoogle Scholar
  48. Katsanos CS, Kobayashi H, Sheffield-Moore M et al (2005) Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr 82(5):1065–1073PubMedGoogle Scholar
  49. Katsanos CS, Kobayashi H, Sheffield-Moore M et al (2006) A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab 291(2):E381–E387PubMedCrossRefGoogle Scholar
  50. Katsanos CS, Chinkes DL, Paddon-Jones D et al (2008) Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content. Nutr Res 28(10):651–658PubMedCrossRefGoogle Scholar
  51. Kimball SR, Jefferson LS (2006a) New functions for amino acids: effects on gene transcription and translation. Am J Clin Nutr 83(2):500S–507SPubMedGoogle Scholar
  52. Kimball SR, Jefferson LS (2006b) Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. J Nutr 136(1 Suppl):227S–231SPubMedGoogle Scholar
  53. Kimball SR, Farrell PA, Jefferson LS (2002) Invited review: role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise. J Appl Physiol 93(3):1168–1180PubMedGoogle Scholar
  54. Kobayashi H, Borsheim E, Anthony TG et al (2003) Reduced amino acid availability inhibits muscle protein synthesis and decreases activity of initiation factor eIF2B. Am J Physiol Endocrinol Metab 284(3):E488–E498PubMedGoogle Scholar
  55. Koopman R, Walrand S, Beelen M et al (2009) Dietary protein digestion and absorption rates and the subsequent postprandial muscle protein synthetic response do not differ between young and elderly men. J Nutr 139(9):1707–1713PubMedCrossRefGoogle Scholar
  56. Landmesser U, Dikalov S, Price SR et al (2003) Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 111(8):1201–1209PubMedGoogle Scholar
  57. Liu Z, Barrett EJ (2002) Human protein metabolism: its measurement and regulation. Am J Physiol Endocrinol Metab 283(6):E1105–E1112PubMedGoogle Scholar
  58. Long X, Ortiz-Vega S, Lin Y et al (2005) Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J Biol Chem 280(25):23433–23436PubMedCrossRefGoogle Scholar
  59. McKinnell IW, Rudnicki MA (2004) Molecular mechanisms of muscle atrophy. Cell 119(7):907–910PubMedCrossRefGoogle Scholar
  60. Meneilly GS, Elliot T, Bryer-Ash M et al (1995) Insulin-mediated increase in blood flow is impaired in the elderly. J Clin Endocrinol Metab 80(6):1899–1903PubMedCrossRefGoogle Scholar
  61. Morley JE (2008) Sarcopenia: diagnosis and treatment. J Nutr Health Aging 12(7):452–456PubMedCrossRefGoogle Scholar
  62. Morley JE (2012) Sarcopenia in the elderly. Fam Pract 29(Suppl 1):i44–i48PubMedCrossRefGoogle Scholar
  63. Nagasawa T, Kido T, Yoshizawa F et al (2002) Rapid suppression of protein degradation in skeletal muscle after oral feeding of leucine in rats. J Nutr Biochem 13(2):121–127PubMedCrossRefGoogle Scholar
  64. Nobukuni T, Joaquin M, Roccio M et al (2005) Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci U S A 102(40):14238–14243PubMedCrossRefGoogle Scholar
  65. Paddon-Jones D, Rasmussen BB (2009) Dietary protein recommendations and the prevention of sarcopenia. Curr Opin Clin Nutr Metab Care 12(1):86–90PubMedCrossRefGoogle Scholar
  66. Paddon-Jones D, Sheffield-Moore M, Zhang XJ et al (2004) Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab 286(3):E321–E328PubMedCrossRefGoogle Scholar
  67. Pennings B, Groen B, de Lange A et al (2012) Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am J Physiol Endocrinol Metab 302(8):E992–E999PubMedCrossRefGoogle Scholar
  68. Prod’homme M, Balage M, Debras E et al (2005) Differential effects of insulin and dietary amino acids on muscle protein synthesis in adult and old rats. J Physiol 563(Pt 1):235–248PubMedGoogle Scholar
  69. Proud CG (2004a) mTOR-mediated regulation of translation factors by amino acids. Biochem Biophys Res Commun 313(2):429–436PubMedCrossRefGoogle Scholar
  70. Proud CG (2004b) Role of mTOR signalling in the control of translation initiation and elongation by nutrients. Curr Top Microbiol Immunol 279:215–244PubMedCrossRefGoogle Scholar
  71. Rasmussen BB, Wolfe RR, Volpi E (2002) Oral and intravenously administered amino acids produce similar effects on muscle protein synthesis in the elderly. J Nutr Health Aging 6(6):358–362PubMedGoogle Scholar
  72. Rennie MJ, Bohe J, Smith K et al (2006) Branched-chain amino acids as fuels and anabolic signals in human muscle. J Nutr 136(1 Suppl):264S–268SPubMedGoogle Scholar
  73. Rieu I, Sornet C, Bayle G et al (2003) Leucine-supplemented meal feeding for 10 days beneficially affects postprandial muscle protein synthesis in old rats. J Nutr 133(4):1198–1205PubMedGoogle Scholar
  74. Rieu I, Balage M, Sornet C et al (2006) Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol 575(Pt 1):305–315PubMedCrossRefGoogle Scholar
  75. Rieu I, Balage M, Sornet C et al (2007) Increased availability of leucine with leucine-rich whey proteins improves postprandial muscle protein synthesis in aging rats. Nutrition 23(4):323–331PubMedCrossRefGoogle Scholar
  76. Roccio M, Bos JL, Zwartkruis FJ (2006) Regulation of the small GTPase Rheb by amino acids. Oncogene 25(5):657–664PubMedCrossRefGoogle Scholar
  77. Rooyackers OE, Adey DB, Ades PA et al (1996) Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. Proc Natl Acad Sci USA 93(26):15364–15369PubMedCrossRefGoogle Scholar
  78. Sattler FR, Castaneda-Sceppa C, Binder EF et al (2009) Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab 94(6):1991–2001PubMedCrossRefGoogle Scholar
  79. Sheffield-Moore M (2000) Androgens and the control of skeletal muscle protein synthesis. Ann Med 32(3):181–186PubMedCrossRefGoogle Scholar
  80. Sheffield-Moore M, Wolfe RR, Gore DC et al (2000) Combined effects of hyperaminoacidemia and oxandrolone on skeletal muscle protein synthesis. Am J Physiol Endocrinol Metab 278(2):E273–E279PubMedGoogle Scholar
  81. Sheffield-Moore M, Yeckel CW, Volpi E et al (2004) Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise. Am J Physiol Endocrinol Metab 287(3):E513–E522PubMedCrossRefGoogle Scholar
  82. Sheffield-Moore M, Dillon EL, Casperson SL et al (2011) A randomized pilot study of monthly cycled testosterone replacement or continuous testosterone replacement versus placebo in older men. J Clin Endocrinol Metab 96(11):E1831–E1837PubMedCrossRefGoogle Scholar
  83. Sindler AL, Delp MD, Reyes R et al (2009) Effects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles. J Physiol 587(Pt 15):3885–3897PubMedCrossRefGoogle Scholar
  84. Steinberg HO, Brechtel G, Johnson A et al (1994) Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 94(3):1172–1179PubMedCrossRefGoogle Scholar
  85. Suryawan A, Nguyen HV, Almonaci RD et al. (2012a) Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway. J Anim Sci Biotechnol 3(3). doi:10.1186/2049-1891-3-3
  86. Suryawan A, Torrazza RM, Gazzaneo MC et al (2012b) Enteral leucine supplementation increases protein synthesis in skeletal and cardiac muscles and visceral tissues of neonatal pigs through mTORC1-dependent pathways. Pediatr Res 71(4 Pt 1):324–331PubMedCrossRefGoogle Scholar
  87. Symons TB, Schutzler SE, Cocke TL et al (2007) Aging does not impair the anabolic response to a protein-rich meal. Am J Clin Nutr 86(2):451–456PubMedGoogle Scholar
  88. Symons TB, Sheffield-Moore M, Wolfe RR et al (2009) A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects. J Am Diet Assoc 109(9):1582–1586PubMedCrossRefGoogle Scholar
  89. Takahashi R, Goto S (1990) Alteration of aminoacyl-tRNA synthetase with age: heat-labilization of the enzyme by oxidative damage. Arch Biochem Biophys 277(2):228–233PubMedCrossRefGoogle Scholar
  90. Thomas DR, Ashmen W, Morley JE et al (2000) Nutritional management in long-term care: development of a clinical guideline. Council for nutritional strategies in long-term care. J Gerontol A Biol Sci Med Sci 55(12):M725–M734PubMedCrossRefGoogle Scholar
  91. Tieland M, van de Rest O, Dirks ML et al (2012) Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 13(8):720–726PubMedCrossRefGoogle Scholar
  92. Timmerman KL, Lee JL, Fujita S et al (2010) Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults. Diabetes 59(11):2764–2771PubMedCrossRefGoogle Scholar
  93. Tipton KD, Gurkin BE, Matin S et al (1999) Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteers. J Nutr Biochem 10(2):89–95PubMedCrossRefGoogle Scholar
  94. Tremblay F, Jacques H, Marette A (2005) Modulation of insulin action by dietary proteins and amino acids: role of the mammalian target of rapamycin nutrient sensing pathway. Curr Opin Clin Nutr Metab Care 8(4):457–462PubMedCrossRefGoogle Scholar
  95. Verhoeven S, Vanschoonbeek K, Verdijk LB et al (2009) Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men. Am J Clin Nutr 89(5):1468–1475PubMedCrossRefGoogle Scholar
  96. Vincent MA, Clerk LH, Lindner JR et al (2006) Mixed meal and light exercise each recruit muscle capillaries in healthy humans. Am J Physiol Endocrinol Metab 290(6):E1191–E1197PubMedCrossRefGoogle Scholar
  97. Volpi E, Ferrando AA, Yeckel CW et al (1998) Exogenous amino acids stimulate net muscle protein synthesis in the elderly. J Clin Invest 101(9):2000–2007PubMedCrossRefGoogle Scholar
  98. Volpi E, Mittendorfer B, Wolf SE et al (1999) Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction. Am J Physiol 277(3 Pt 1):E513–E520PubMedGoogle Scholar
  99. Volpi E, Mittendorfer B, Rasmussen BB et al (2000) The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J Clin Endocrinol Metab 85(12):4481–4490PubMedCrossRefGoogle Scholar
  100. Volpi E, Sheffield-Moore M, Rasmussen BB et al (2001) Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. JAMA 286(10):1206–1212PubMedCrossRefGoogle Scholar
  101. Volpi E, Kobayashi H, Sheffield-Moore M et al (2003) Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. Am J Clin Nutr 78(2):250–258PubMedGoogle Scholar
  102. Walker DK, Dickinson JM, Timmerman KL et al (2011) Exercise, amino acids, and aging in the control of human muscle protein synthesis. Med Sci Sports Exerc 43(12):2249–2258PubMedCrossRefGoogle Scholar
  103. Wall BT, Dirks ML, Verdijk LB et al (2012) Neuromuscular electrical stimulation increases muscle protein synthesis in elderly, type 2 diabetic men. Am J Physiol Endocrinol Metab 303(5):E614–E623PubMedCrossRefGoogle Scholar
  104. Walrand S, Short KR, Bigelow ML et al (2008) Functional impact of high protein intake on healthy elderly people. Am J Physiol Endocrinol Metab 295(4):E921–E928PubMedCrossRefGoogle Scholar
  105. Wang X, Campbell LE, Miller CM et al (1998) Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem J 334(Pt 1):261–267PubMedGoogle Scholar
  106. Wang Y, Zhang L, Zhou G et al (2012) Dietary l-arginine supplementation improves the intestinal development through increasing mucosal Akt and mammalian target of rapamycin signals in intra-uterine growth retarded piglets. Br J Nutr 108(8):1371–1381PubMedCrossRefGoogle Scholar
  107. Watt PW, Corbett ME, Rennie MJ (1992) Stimulation of protein synthesis in pig skeletal muscle by infusion of amino acids during constant insulin availability. Am J Physiol 263(3 Pt 1):E453–E460PubMedGoogle Scholar
  108. Welle S, Thornton C, Jozefowicz R et al (1993) Myofibrillar protein synthesis in young and old men. Am J Physiol 264(5 Pt 1):E693–E698PubMedGoogle Scholar
  109. Wolfe RR (2006) The underappreciated role of muscle in health and disease. Am J Clin Nutr 84(3):475–482PubMedGoogle Scholar
  110. Wu G (1998) Intestinal mucosal amino acid catabolism. J Nutr 128(8):1249–1252PubMedGoogle Scholar
  111. Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37(1):1–17PubMedCrossRefGoogle Scholar
  112. Wu G, Meininger CJ (2002) Regulation of nitric oxide synthesis by dietary factors. Annu Rev Nutr 22:61–86PubMedCrossRefGoogle Scholar
  113. Wu G, Jaeger LA, Bazer FW et al (2004) Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. J Nutr Biochem 15(8):442–451PubMedCrossRefGoogle Scholar
  114. Xi P, Jiang Z, Dai Z et al (2011) Regulation of protein turnover by l-glutamine in porcine intestinal epithelial cells. J Nutr Biochem 23(8):1012–1017PubMedCrossRefGoogle Scholar
  115. Xu G, Kwon G, Marshall CA et al (1998) Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6 kinase by pancreatic beta-cells. A possible role in protein translation and mitogenic signaling. J Biol Chem 273(43):28178–28184PubMedCrossRefGoogle Scholar
  116. Yang Y, Churchward-Venne TA, Burd NA et al (2012) Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. Nutr Metab (Lond) 9(1):57CrossRefGoogle Scholar
  117. Yao K, Yin YL, Chu W et al (2008) Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs. J Nutr 138(5):867–872PubMedGoogle Scholar
  118. Yarasheski KE, Zachwieja JJ, Bier DM (1993) Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. Am J Physiol 265(2 Pt 1):E210–E214PubMedGoogle Scholar
  119. Yarasheski KE, Castaneda-Sceppa C, He J et al (2011) Whole-body and muscle protein metabolism are not affected by acute deviations from habitual protein intake in older men: the Hormonal Regulators of Muscle and Metabolism in Aging (HORMA) Study. Am J Clin Nutr 94(1):172–181PubMedCrossRefGoogle Scholar
  120. Zhang L, Vincent MA, Richards SM et al (2004) Insulin sensitivity of muscle capillary recruitment in vivo. Diabetes 53(2):447–453PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  1. 1.Division of Endocrinology and Metabolism, Department of Internal MedicineThe University of Texas Medical BranchGalvestonUSA

Personalised recommendations