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Leucine: a key amino acid in ageing-associated sarcopenia?

Published online by Cambridge University Press:  01 November 2007

Dominique Dardevet ,
Isabelle Rieu ,
Pierre Fafournoux ,
Claire Sornet ,
Lydie Combaret ,
Alain Bruhat ,
Sylvie Mordier ,
Laurent Mosoni  and
Jean Grizard
Dominique Dardevet*
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
Isabelle Rieu
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
Pierre Fafournoux
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
Claire Sornet
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
Lydie Combaret
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
Alain Bruhat
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
Sylvie Mordier
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
Laurent Mosoni
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
Jean Grizard
Affiliation:
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Theix, 63122 Saint-Genès-Champanelle, France
*
*Corresponding author: Dr Dominique Dardevet, fax +33 4 73 62 47 55, email Dominique.Dardevet@clermont.inra.fr
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Abstract

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During ageing, a progressive loss of muscle mass has been well described in both man and rodents. This loss of proteins results from an imbalance between protein synthesis and degradation rates. Although some authors have shown a decrease of myofibrillar protein synthesis rates in human volunteers, this imbalance is not clearly apparent when basal rates of protein turnover are measured. A decrease in muscle protein synthesis stimulation was detected nevertheless in ageing rats during the postprandial period, suggesting that the ‘meal signal’ was altered during ageing. Many results now suggest that aged muscle is less sensitive to the stimulatory effect of amino acids at physiological concentrations but is still able to respond if the increase in aminoacidaemia is sufficiently large. Indeed amino acids play an important role in regulating muscle protein turnover both in vitro and in vivo. At the molecular level, amino acids modulate gene expression. Amino acid response elements have been characterised in the promoter of transcriptional factor CCAAT-enhancer binding protein homologous protein and asparagine synthetase genes. Among amino acids, leucine seems to play the major role in regulating the metabolic function. It inhibits proteolysis and stimulates muscle protein synthesis independently of insulin. Leucine has been shown to act as a real mediator by modulating specifically the activities of intracellular kinases linked to the translation of proteins such as phosphatidylinosinol 3′ kinase and mammalian target of rapamycin–70 kDa ribosomal protein S6 (p70S6K) kinases. We recently demonstrated in vitro that protein synthesis of ageing rat muscles becomes resistant to the stimulatory effect of leucine in its physiological concentration range. However, when leucine concentration was increased greatly above its postprandial level, protein synthesis was stimulated normally. Moreover, we studied the effect of meal leucine supplementation on in vivo protein synthesis in adult and ageing rats. Leucine supplementation had no additional effect on muscle protein synthesis in adults but totally restored its stimulation in ageing rats. Whether chronic oral leucine supplementation would be beneficial for maintaining muscle protein mass in elderly men and women remains to be studied.

Keywords

AgeingLeucineAmino acidsSarcopenia
Type
Research Article
Information
Nutrition Research Reviews , Volume 16 , Issue 1 , June 2003 , pp. 61 - 70
Copyright
Copyright © CABI Publishing 2003

References

Anthony, JC, Anthony, TG, Kimball, SR & Jefferson, LS (2001) Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. Journal of Nutrition 131, 856S–860S.CrossRefGoogle ScholarPubMed
Anthony, JC, Anthony, TG, Kimball, SR, Vary, TC & Jefferson, LS (2000 a) Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased elF4F formation. Journal of Nutrition 130, 139–145.Google Scholar
Anthony, JC, Yoshizawa, F, Anthony, TG, Vary, TC, Jefferson, LS & Kimball, SR (2000 b) Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. Journal of Nutrition 130, 2413–2419.CrossRefGoogle Scholar
Arnal, MA, Mosoni, L, Boirie, Y, Gachon, P, Genest, M, Bayle, G, Grizard, J, Arnal, M, Antoine, JM, Beaufrère, B & Patureau Mirand, P (2000) Protein turnover modifications induced by the protein feeding pattern still persist after the end of dietary treatments. American Journal of Physiology 278, E902–E909.Google Scholar
Arnal, MA, Mosoni, L, Boirie, Y, Houlier, ML, Morin, L, Verdier, E, Ritz, P, Antoine, JM, Prugnaud, J, Beaufrère, B & Patureau Mirand, P (1999) Protein pulse feeding improves protein retention in elderly women. American Journal of Clinical Nutrition 69, 1202–1208.Google Scholar
Attaix, D, Aurousseau, E, Manghebati, A & Arnal, M (1988) Contribution of liver, skin and skeletal muscle to whole-body protein synthesis in the young lamb. British Journal of Nutrition 60, 77–84.Google Scholar
Balage, M, Sinaud, S, Prod'homme, M, Dardevet, D, Vary, TC, Kimball, SR, Jefferson, LS & Grizard, J (2001) Amino acids and insulin are both required for regulating assembly of the elF4E-elF4G complex in rat skeletal muscle. American Journal of Physiology 281, E565–E574.Google ScholarPubMed
Balagopal, P, Rooyackers, OE, Adey, DB, Ades, PA & Nair, KS (1997) Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans. American Journal of Physiology 273, E790–E800.Google ScholarPubMed
Barbosa-Tessmann, IP, Chen, C, Zhong, C, Schuster, SM, Nick, HS & Kilberg, MS (1999) Activation of the unfolded protein response pathway induces human asparagine synthetase gene expression. Journal of Biological Chemistry 274, 31139–31144.Google Scholar
Barbosa-Tessmann, IP, Chen, C, Zhong, C, Siu, F, Schuster, SM, Nick, HS & Kilberg, MS (2000) Activation of the human asparagine synthetase gene by the amino acid response and the endoplasmic reticulum stress response pathways occurs by common genomic elements. Journal of Biological Chemistry 275, 26976–26985.Google Scholar
Bergström, J, Furst, P & Vinnars, E (1990) Effect of a test meal, without and with protein, on muscle and plasma free amino acids. Clinical Science 79, 331–337.CrossRefGoogle ScholarPubMed
Berlanga, JJ, Santoyo, J & De Haro, C (1999) Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2 alpha kinase. European Journal of Biochemistry 265, 754–762.CrossRefGoogle Scholar
Boirie, Y, Gachon, P & Beaufrère, B (1997) Splanchnic and whole-body leucine kinetics in young and elderly men. American Journal of Clinical Nutrition 65, 489–495.Google Scholar
Boirie, Y, Gachon, P, Corny, S, Fauquant, J, Maubois, JL & Beaufrère, B (1996) Acute postprandial changes in leucine metabolism as assessed with an intrinsically labeled milk protein. American Journal of Physiology 271, E1083–E1091.Google Scholar
Bruhat, A & Fafournoux, P (2001) Recent advances on molecular mechanisms involved in amino acid control of gene expression. Current Opinion in Clinical Nutrition and Metabolic Care 4, 439–443.Google Scholar
Bruhat, A, Jousse, C, Carraro, V, Reimold, A, Ferrara, M & Fafournoux, P (2000) Amino acids control mammalian gene transcription: Activating transcription factor 2 is essential for the amino-acid responsiveness of the CHOP promoter. Molecular and Cellular Biology 20, 7192–7204.CrossRefGoogle ScholarPubMed
Bruhat, A, Jousse, C, Wang, XZ, Ron, D, Ferrara, M & Fafournoux, P (1997) Amino acid limitation induces expression of CHOP, a CCAAT/enhancer binding protein-related gene, at both transcriptional and post-transcriptional levels. Journal of Biological Chemistry 272, 17588–17593.Google Scholar
Buse, MG, Jursinic, S & Reid, SS (1975) Regulation of branched-chain amino acid oxidation in isolated|muscles, nerves and aortas of rats. Biochemical Journal 148, 363–374.Google Scholar
Busquets, S, Alvarez, B, Llovera, M, Agell, N, Lopez-Soriano, FJ & Argiles, JM (2000) Branched-chain amino acids inhibit proteolysis in rat skeletal muscle: Mechanisms involved. Journal of Cellular Physiology 184, 380–384.Google Scholar
Carlson, BM (1992) Muscle regeneration and aging. In Keys for Regeneration, pp. 189–195 [Taban, CH and Boilly, B editors]. Basel: Karger.Google Scholar
Cohn, SH, Vartsky, D, Yasumura, S, Sawitsky, A, Zanzi, I, Waswani, A & Ellis, KJ (1980) Compartmental body composition based on total-body nitrogen, potassium, and calcium. American Journal of Physiology 239, E524–E530.Google ScholarPubMed
Dardevet, D, Sornet, C, Attaix, D, Baracos, VE & Grizard, J (1994) Insulin-like Growth Factor-1 and insulin resistance in skeletal muscles of adult and old rats. Endocrinology 134, 1475–1484.CrossRefGoogle ScholarPubMed
Dardevet, D, Sornet, C, Balage, M & Grizard, J (2000) Stimulation of in vitro rat muscle protein synthesis by leucine decreases with age. Journal of Nutrition 130, 2630–2635.Google Scholar
Dardevet, D, Sornet, C, Bayle, G, Prugnaud, J, Pouyet, C & Grizard, J (2002) Post-prandial stimulation of muscle protein synthesis in old rats was restored by a leucine supplemented meal. Journal of Nutrition 132, 95–100.Google Scholar
El Haj, AJ, Lewis, SE, Goldspink, DF, Merry, BJ & Holehan, AM (1986) The effect of chronic and acute dietary restriction on the growth and protein turnover of fast and slow types of rat skeletal muscle. Comparative Biochemistry and Physiology 85A, 281–287.CrossRefGoogle Scholar
Elia, M, Folmer, P, Schlatmann, A, Goren, A & Austin, S (1989) Amino acid metabolism in muscle and in the whole body of man before and after ingestion of a single mixed meal. American Journal of Clinical Nutrition 49, 1203–1210.Google Scholar
Evans, JL, Honer, CM, Womelsdorf, BE, Kaplan, EL & Bell, PA (1995) The effects of wortmannin, a potent inhibitor of phosphatidyl-inositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis. Cellular Signalling 7, 365–376.Google Scholar
Fereday, A, Gibson, NR, Cox, M, Pacy, PJ & Millward, DJ (1998) Variation in the apparent sensitivity of the insulin-mediated inhibition of proteolysis to amino acid supply determines the efficiency of protein utilization. Clinical Science 95, 725–733.Google Scholar
Forbes, GB & Reina, JC (1970) Adult lean body mass declines with age: some longitudinal observations. Metabolism 19, 653–663.Google Scholar
Frexes-Steed, M, Warner, ML, Bulus, N, Flakoll, P & Abumrad, NN (1990) Role of insulin and branched-chain amino acids in regulating protein metabolism during fasting. American Journal of Physiology 258, E907–E917.Google Scholar
Fulks, R, Li, JB & Goldberg, AL (1975) Effects of insulin, glucose and amino acids on protein turnover in rat diaphragm. Journal of Biological Chemistry 250, 290–298.Google Scholar
Funabiki, R, Yagasaki, K, Hara, H, Nyumura, N, Yoshizawa, F & Saito, K (1992) In vivo effect of L-leucine administration on protein synthesis in mice. Journal of Nutritional Biochemistry 3, 401–407.Google Scholar
Garlick, PJ, Fern, M & Preedy, VR (1983) The effect of insulin infusion and food intake on muscle protein synthesis in postabsorptive rats. Biochemical Journal 210, 669–676.Google Scholar
Garlick, PJ & Grant, I (1988) Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched-chain amino acids. Biochemical Journal 254, 579–584.Google Scholar
Harding, HP, Novoa, I, Zhang, Y, Zeng, H, Wek, R, Schapira, M & Ron, D (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular and Cellular Biology 6, 1099–1108.Google ScholarPubMed
Hinnebusch, AG (1994) Translational control of GCN4: an in vivo barometer of initiation-factor activity. Trends in Biochemical Science 19, 409–414.CrossRefGoogle Scholar
Holloszy, JO, Chen, M, Cartee, GD & Young, JC (1991) Skeletal muscle atrophy in old rats: differential changes in the three fiber types. Mechanisms of Ageing and Development 60, 199–213.Google Scholar
Holloszy, JO, Smith, EK, Vining, M & Adams, SA (1985) Effect of voluntary exercise on longevity of rats. Journal of Applied Physiology 59, 826–831.Google Scholar
Kelly, FJ & Jefferson, LS (1985) Control of peptide-chain initiation in rat skeletal muscle. Development of methods for preparation of native ribosomal subunits and analysis of the effect of insulin on formation of 40S initiation complexes. Journal of Biological Chemistry 260, 6677–6683.Google Scholar
Kelly, FJ, Lewis, SEM, Anderson, P & Goldspink, DF (1984) Pre- and postnatal growth and protein turnover in four muscles of the rat. Muscle and Nerve 7, 235–242.Google Scholar
Kimball, SR, Jefferson, LS, Fadden, P, Haystead, TAJ & Lawrence, JC (1996) Insulin and diabetes cause reciprocal changes in the association of eIF-4E and PHAS-I in rat skeletal muscle. American Journal of Physiology 270, C705–C709.Google Scholar
Kimball, SR, Shantz, LM, Horetsky, RL & Jefferson, LS (1999) Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6. Journal of Biological Chemistry 274, 11647–11652.CrossRefGoogle ScholarPubMed
Lewis, SEM, Kelly, FJ & Goldspink, DF (1984) Pre- and post-natal growth and protein turnover in smooth muscle, heart and slow- and fast-twitch skeletal muscles of the rat. Biochemical Journal 217, 517–526.Google Scholar
Li, JB & Jefferson, LS (1978) Influence of amino acid availability on protein turnover in perfused skeletal muscle. Biochimica et Biophysica Acta 544, 351–359.CrossRefGoogle ScholarPubMed
Louard, RJ, Barrett, EJ & Gelfand, RA (1990) Effect of infused branched-chain amino acids on muscle and whole-body amino acid metabolism in man. Clinical Science 79, 457–466.Google Scholar
McNurlan, M, Fern, EB & Garlick, PJ (1982) Failure of leucine to stimulate protein synthesis in vivo. Biochemical Journal 204, 831–838.CrossRefGoogle ScholarPubMed
Mays, PK, McAnulty, RJ & Laurent, GJ (1991) Age-related changes in rates of protein synthesis and degradation in rat tissues. Mechanisms of Ageing and Development 59, 229–241.Google Scholar
Millward, DJ, Bowtell, JL, Pacy, P & Rennie, MJ (1994) Physical activity, protein metabolism and protein requirements. Proceedings of the Nutrition Society 53, 223–240.Google Scholar
Millward, DJ, Fereday, A, Gibson, N & Pacy, PJ (1997) Aging, protein requirements, and protein turnover. American Journal of Clinical Nutrition 66, 774–786.Google Scholar
Millward, DJ, Garlick, PJ, Stewart, RJ, Nnanyelugo, DO & Waterlow, JC (1975) Skeletal-muscle growth and protein turnover. Biochemical Journal 150, 235–243.Google Scholar
Millward, DJ, Odedra, B & Bates, PC (1983) The role of insulin, corticosterone and other factors in the acute recovery of muscle protein synthesis on refeeding food-deprived rats. Biochemical Journal 216, 583–587.Google Scholar
Mordier, S, Deval, C, Béchet, D, Tassa, A & Ferrara, M (2000) Leucine limitation induces autophagy and activation of lysosome-dependent proteolysis in C2C12 myotubes through a mammalian target of Rapamycin-independent signaling pathway. Journal of Biological Chemistry 275, 29900–29906.Google Scholar
Mosoni, L, Houlier, ML, Patureau Mirand, P, Bayle, G & Grizard, J (1993) Effect of amino acids alone or with insulin on muscle and liver protein synthesis in adult and old rats. American Journal of Physiology 264, E614–E620.Google Scholar
Mosoni, L, Malmezat, T, Valluy, MC, Houlier, ML, Attaix, D & Patureau Mirand, P (1999) Lower recovery of muscle protein lost during starvation in old rats despite a stimulation of protein synthesis. American Journal of Physiology 277, E608–E616.Google Scholar
Mosoni, L, Patureau Mirand, P, Houlier, ML & Arnal, M (1993) Age-related changes in protein synthesis measured in vivo in rat liver and gastrocnemius muscle. Mechanisms of Ageing and Development 68, 209–220.Google Scholar
Mosoni, L, Valluy, MC, Serrurier, B, Prugnaud, J, Obled, C, Guezennec, CY & Patureau Mirand, P (1995) Altered response of protein synthesis to nutritional state and endurance training in old rats. American Journal of Physiology 268, E328–E335.Google Scholar
Nair, KS, Ford, GC, Ekberg, K, Fernqvist-Forbes, E & Wahren, J (1995) Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients. Journal of Clinical Investigation 95, 2926–2937.Google Scholar
Nair, KS, Matthews, DE, Welle, SL & Braiman, T (1992) Effect of leucine on amino acid and glucose metabolism in humans. Metabolism – Clinical and Experimental 41, 643–648.Google Scholar
Nair, KS, Welle, SL, Halliday, D & Campbell, RG (1988) Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. Journal of Clinical Investigation 82, 198–205.Google Scholar
Pacy, PJ, Price, GM, Halliday, D, Quevedo, MR & Millward, DJ (1994) Nitrogen homoeostasis in man – the diurnal responses of protein synthesis and degradation and amino acid oxidation to diets with increasing protein intakes. Clinical Science 86, 103–118.Google Scholar
Pain, VM (1996) Initiation of protein synthesis in eukaryotic cells. European Journal of Biochemistry 236, 747–771.Google Scholar
Papet, I, Glomot, F, Grizard, J & Arnal, M (1992) Leucine excess under conditions of low or compensated aminoacidemia does not change skeletal muscle and whole-body protein synthesis in suckling lambs during the postprandial period. Journal of Nutrition 122, 2307–2315.CrossRefGoogle Scholar
Patti, ME, Brambilla, E, Luzi, L, Landaker, EJ & Kahn, CR (1998) Bidirectional modulation of insulin action by amino acids. Journal of Clinical Investigation 101, 1519–1529.CrossRefGoogle ScholarPubMed
Preedy, VR & Garlick, PJ (1986) The response of muscle protein synthesis to nutrient intake in postabsorptive rats: the role of insulin and amino acids. Bioscience Reports 6, 177–183.Google Scholar
Rennie, MJ, Edwards, RH, Halliday, D, Matthews, DE, Wolman, SL & Millward, DJ (1982) Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting. Clinical Science 63, 519–523.Google Scholar
Rhoads, RE (1999) Signal transduction pathways that regulate eukaryotic protein synthesis. Journal of Biological Chemistry 274, 30337–30340.Google Scholar
Rhoads, RE, Joshibarve, S & Rinker-Schaeffer, C (1993) Mechanism of action and regulation of protein synthesis initiation factor 4E: effects on mRNA|discrimination, cellular growth|rate, and oncogenesis. In Progress in Nucleic Acid Research and Molecular Biology, pp. 183–219 [Cohn, WE and Moldave, K editors]. Academic Press.Google Scholar
Rooyackers, OE, Adey, DB, Ades, PA & Nair, KS (1996) Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. Proceedings of the National Academy of Sciences USA 93, 15364–15369.Google Scholar
Rowe, JW (1980) Aging and renal function. Annual Review of Gerontology and Geriatrics 1, 161–179.Google Scholar
Schneider, EL & Guralnik, JM (1990) The aging of America. Impact on health care costs. Journal of the American Medical Association 263, 2335–2340.Google Scholar
Shah, OJ, Anthony, JC, Kimball, SR & Jefferson, LS (2000) 4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle. American Journal of Physiology 279, E715–E729.Google Scholar
Sinaud, S, Balage, M, Bayle, G, Dardevet, D, Vary, TC, Kimball, SR, Jefferson, LS & Grizard, J (1999) Diazoxide-induced insulin deficiency greatly reduced muscle protein synthesis in rats: involvement of EIF4E. American Journal of Physiology 276, E50–E61.Google Scholar
Sood, R, Porter, AC, Olsen, DA, Cavener, DR & Wek, RC (2000) A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2alpha. Genetics 154, 787–801.Google Scholar
Svanberg, E, Jefferson, LS, Lundholm, K & Kimball, SR (1997) Postprandial stimulation of muscle protein synthesis is independent of changes in insulin. American Journal of Physiology 272, E841–E847.Google Scholar
Svanberg, E, Zachrisson, H, Ohlsson, C, Iresjö, BM & Lundholm, KG (1996) Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding. American Journal of Physiology 270, E614–E620.Google Scholar
Taylor, AW, Noble, EG, Cunningham, DA, Paterson, DH & Rechnitzer, P (1992) Ageing, skeletal muscle contractile properties and enzyme activities with exercise. In Integration of Medical and Sports Sciences., pp.109–125 [Sato, Y, Poortmans, J, Hashimoto, I and Oshida, Y editors]. Basel: Karger.Google Scholar
Volpi, E, Lucidi, P, Cruciani, G, Monacchia, F, Reboldi, G, Brunetti, P, Bolli, GB & De Feo, P (1996) Contribution of amino acids and insulin to protein anabolism during meal absorption. Diabetes 45, 1245–1252.CrossRefGoogle ScholarPubMed
Volpi, E, Mittendorfer, B, Rasmussen, BB & Wolfe, RR (2000) The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. Journal of Clinical Endocrinology and Metabolism 85, 4481–4490.Google Scholar
Volpi, E, Mittendorfer, B, Wolf, SE & Wolfe, RR (1999) Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction. American Journal of Physiology 277, E513–E520.Google Scholar
Volpi, E & Rasmussen, BB (2000) Nutrition and muscle protein metabolism in the elderly. Diabetes Nutrition and Metabolism 13, 99–107.Google Scholar
Waterlow, JC, Golden, MH & Garlick, PJ (1978) Protein turnover in man measured with 15N: comparison of end products and dose regimes. American Journal of Physiology 235, E165–E174.Google Scholar
Welle, S, Statt, M, Barnard, R & Amatruda, J (1994) Differential effect of insulin on whole-body proteolysis and glucose metabolism in normal-weight, obese, and reduced-obese women. Metabolism – Clinical and Experimental 43, 441–445.Google Scholar
Welle, S, Thornton, C, Jozefowicz, R & Statt, M (1993) Myofibrillar protein synthesis in young and old men. American Journal of Physiology 264, E693–E698.Google Scholar
Yarasheski, KE, Campbell, JA, Smith, K, Rennie, MJ, Holloszy, JO & Bier, DM (1992) Effect of growth hormone and resistance exercise on muscle growth in young men. American Journal of Physiology 262, E261–E267.Google Scholar
Yarasheski, KE, Zachwieja, JJ & Bier, DM (1993) Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. American Journal of Physiology 265, E210–E214.Google Scholar
Yarasheski, KE, Zachwieja, JJ, Campbell, JA & Bier, DM (1995) Effect of growth hormone and resistance exercise on muscle growth and strength in older men. American Journal of Physiology 268, E268–E276.Google ScholarPubMed
Yoshizawa, F, Endo, M, Ide, H, Yagasaki, K & Funabiki, R (1995) Translational regulation of protein synthesis in the liver and skeletal muscle of mice in response to refeeding. Journal of Nutritional Biochemistry 6, 130–136.Google Scholar
Yoshizawa, F, Kimball, SR & Jefferson, LS (1997 a) Modulation of translation initiation in rat skeletal muscle and liver in response to food intake. Biochemical and Biophysical Research Communications 240, 825–831.Google Scholar
Yoshizawa, F, Kimball, SR, Vary, TC & Jefferson, LS (1998) Effect of dietary protein on translation initiation in rat skeletal muscle and liver. American Journal of Physiology 275, E814–E820.Google Scholar
Yoshizawa, F, Nagasawa, T, Nishizawa, N & Funabiki, R (1997 b) Protein synthesis and degradation change rapidly in response to food intake in muscle of food-deprived mice. Journal of Nutrition 127, 1156–1159.CrossRefGoogle ScholarPubMed
Young, VR & Munro, HN (1978) N tau-methylhistidine (3-methylhistidine) and muscle protein turnover: an overview. Federation Proceedings 37, 2291–2300.Google ScholarPubMed
Young, VR, Steffee, WP, Pencharz, PB, Winterer, JC & Scrimshaw, NS (1975) Total human body synthesis in relation to protein requirements at various ages. Nature 253, 192–194.Google Scholar