Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. 1998 May 1; 101(9): 2000–2007.
PMCID: PMC508787

Exogenous amino acids stimulate net muscle protein synthesis in the elderly.


We have investigated the response of amino acid transport and protein synthesis in healthy elderly individuals (age 71+/-2 yr) to the stimulatory effect of increased amino acid availability. Muscle protein synthesis and breakdown, and amino acid transport were measured in the postabsorptive state and during the intravenous infusion of an amino acid mixture. Muscle-free amino acid kinetics were calculated by means of a three compartment model using data obtained by femoral arterio-venous catheterization and muscle biopsies from the vastus lateralis during the infusion of stable isotope tracers of amino acids. In addition, muscle protein fractional synthetic rate (FSR) was measured. Peripheral amino acid infusion significantly increased amino acid delivery to the leg, amino acid transport, and muscle protein synthesis when measured either with the three compartment model (P < 0.05) or with the traditional precursor-product approach (FSR increased from 0. 0474+/-0.0054 to 0.0940+/-0.0143%/h, P < 0.05). Because protein breakdown did not change during amino acid infusion, a positive net balance of amino acids across the muscle was achieved. We conclude that, although muscle mass is decreased in the elderly, muscle protein anabolism can nonetheless be stimulated by increased amino acid availability. We thus hypothesize that muscle mass could be better maintained with an increased intake of protein or amino acids.

Full Text

The Full Text of this article is available as a PDF (222K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Welle S, Thornton C, Jozefowicz R, Statt M. Myofibrillar protein synthesis in young and old men. Am J Physiol. 1993 May;264(5 Pt 1):E693–E698. [PubMed]
  • Yarasheski KE, Zachwieja JJ, Bier DM. Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. Am J Physiol. 1993 Aug;265(2 Pt 1):E210–E214. [PubMed]
  • Welle S, Thornton C, Statt M, McHenry B. Postprandial myofibrillar and whole body protein synthesis in young and old human subjects. Am J Physiol. 1994 Oct;267(4 Pt 1):E599–E604. [PubMed]
  • Rooyackers OE, Adey DB, Ades PA, Nair KS. Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15364–15369. [PMC free article] [PubMed]
  • Welle S, Bhatt K, Thornton C. Polyadenylated RNA, actin mRNA, and myosin heavy chain mRNA in young and old human skeletal muscle. Am J Physiol. 1996 Feb;270(2 Pt 1):E224–E229. [PubMed]
  • Watt PW, Corbett ME, Rennie MJ. Stimulation of protein synthesis in pig skeletal muscle by infusion of amino acids during constant insulin availability. Am J Physiol. 1992 Sep;263(3 Pt 1):E453–E460. [PubMed]
  • Bennet WM, Connacher AA, Scrimgeour CM, Smith K, Rennie MJ. Increase in anterior tibialis muscle protein synthesis in healthy man during mixed amino acid infusion: studies of incorporation of [1-13C]leucine. Clin Sci (Lond) 1989 Apr;76(4):447–454. [PubMed]
  • Fryburg DA, Jahn LA, Hill SA, Oliveras DM, Barrett EJ. Insulin and insulin-like growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms. J Clin Invest. 1995 Oct;96(4):1722–1729. [PMC free article] [PubMed]
  • Bennet WM, Connacher AA, Scrimgeour CM, Rennie MJ. The effect of amino acid infusion on leg protein turnover assessed by L-[15N]phenylalanine and L-[1-13C]leucine exchange. Eur J Clin Invest. 1990 Feb;20(1):41–50. [PubMed]
  • Biolo G, Tipton KD, Klein S, Wolfe RR. An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein. Am J Physiol. 1997 Jul;273(1 Pt 1):E122–E129. [PubMed]
  • Rudman D, Mattson DE, Feller AG, Cotter R, Johnson RC. Fasting plasma amino acids in elderly men. Am J Clin Nutr. 1989 Mar;49(3):559–566. [PubMed]
  • Newton RB, Sullivan JL, Debusk AG. Neutral amino acid transport and in vitro aging. Mech Ageing Dev. 1984 Sep;27(1):63–72. [PubMed]
  • Sambuy Y, Bittles AH. The effects of in vitro ageing on the composition of the intracellular free amino acid pool of human diploid fibroblasts. Mech Ageing Dev. 1982 Dec;20(4):279–287. [PubMed]
  • Leoni S, Spagnuolo S, Dini L, Massimi M, Conti Devirgiliis L. Regulation of amino acid transport in hepatocytes isolated from adult and old rats. Mech Ageing Dev. 1988 Dec;46(1-3):19–27. [PubMed]
  • Sakurai Y, Aarsland A, Herndon DN, Chinkes DL, Pierre E, Nguyen TT, Patterson BW, Wolfe RR. Stimulation of muscle protein synthesis by long-term insulin infusion in severely burned patients. Ann Surg. 1995 Sep;222(3):283–297. [PMC free article] [PubMed]
  • Ferrando AA, Stuart CA, Brunder DG, Hillman GR. Magnetic resonance imaging quantitation of changes in muscle volume during 7 days of strict bed rest. Aviat Space Environ Med. 1995 Oct;66(10):976–981. [PubMed]
  • Biolo G, Declan Fleming RY, Wolfe RR. Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest. 1995 Feb;95(2):811–819. [PMC free article] [PubMed]
  • Calder AG, Anderson SE, Grant I, McNurlan MA, Garlick PJ. The determination of low d5-phenylalanine enrichment (0.002-0.09 atom percent excess), after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography/electron ionization mass spectrometry. Rapid Commun Mass Spectrom. 1992 Jul;6(7):421–424. [PubMed]
  • Biolo G, Fleming RY, Maggi SP, Wolfe RR. Transmembrane transport and intracellular kinetics of amino acids in human skeletal muscle. Am J Physiol. 1995 Jan;268(1 Pt 1):E75–E84. [PubMed]
  • Jorfeldt L, Wahren J. Leg blood flow during exercise in man. Clin Sci. 1971 Nov;41(5):459–473. [PubMed]
  • Jorfeldt L, Juhlin-Dannfelt A. The influence of ethanol on splanchnic and skeletal muscle metabolism in man. Metabolism. 1978 Jan;27(1):97–106. [PubMed]
  • Chinkes DL, Rosenblatt J, Wolfe RR. Assessment of the mathematical issues involved in measuring the fractional synthesis rate of protein using the flooding dose technique. Clin Sci (Lond) 1993 Feb;84(2):177–183. [PubMed]
  • Rivas T, Urcelay E, González-Manchón C, Parrilla R, Ayuso MS. Role of amino acid-induced changes in ion fluxes in the regulation of hepatic protein synthesis. J Cell Physiol. 1995 May;163(2):277–284. [PubMed]
  • Lundholm K, Bennegård K, Zachrisson H, Lundgren F, Edén E, Möller-Loswick AC. Transport kinetics of amino acids across the resting human leg. J Clin Invest. 1987 Sep;80(3):763–771. [PMC free article] [PubMed]
  • Brundin T, Wahren J. Effects of i.v. amino acids on human splanchnic and whole body oxygen consumption, blood flow, and blood temperatures. Am J Physiol. 1994 Mar;266(3 Pt 1):E396–E402. [PubMed]
  • Meneilly GS, Elliot T, Bryer-Ash M, Floras JS. Insulin-mediated increase in blood flow is impaired in the elderly. J Clin Endocrinol Metab. 1995 Jun;80(6):1899–1903. [PubMed]
  • Mosoni L, Houlier ML, Mirand PP, Bayle G, Grizard J. Effect of amino acids alone or with insulin on muscle and liver protein synthesis in adult and old rats. Am J Physiol. 1993 Apr;264(4 Pt 1):E614–E620. [PubMed]
  • Morgan DB, Newton HM, Schorah CJ, Jewitt MA, Hancock MR, Hullin RP. Abnormal indices of nutrition in the elderly: a study of different clinical groups. Age Ageing. 1986 Mar;15(2):65–76. [PubMed]
  • Fiatarone MA, Evans WJ. The etiology and reversibility of muscle dysfunction in the aged. J Gerontol. 1993 Sep;48(Spec No):77–83. [PubMed]
  • Blaum CS, Fries BE, Fiatarone MA. Factors associated with low body mass index and weight loss in nursing home residents. J Gerontol A Biol Sci Med Sci. 1995 May;50(3):M162–M168. [PubMed]
  • Campbell WW, Crim MC, Dallal GE, Young VR, Evans WJ. Increased protein requirements in elderly people: new data and retrospective reassessments. Am J Clin Nutr. 1994 Oct;60(4):501–509. [PubMed]
  • Campbell WW, Evans WJ. Protein requirements of elderly people. Eur J Clin Nutr. 1996 Feb;50 (Suppl 1):S180–S185. [PubMed]
  • Roberts SB, Fuss P, Heyman MB, Young VR. Influence of age on energy requirements. Am J Clin Nutr. 1995 Nov;62(5 Suppl):1053S–1058S. [PubMed]
  • Reilly JJ, Lord A, Bunker VW, Prentice AM, Coward WA, Thomas AJ, Briggs RS. Energy balance in healthy elderly women. Br J Nutr. 1993 Jan;69(1):21–27. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...