QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dardevet, D. Articles by Grizard, J. Search for Related Content PubMed PubMed Citation Articles by Dardevet, D. Articles by Grizard, J.

---

Articles

Stimulation of In Vitro Rat Muscle Protein Synthesis by Leucine Decreases with Age¹

Human Nutrition Research Center of Clermont-Ferrand and Institut National de la Recherche Agronomique, Unité d’Etude du Métabolisme Azoté, 63122 Ceyrat, France

²To whom correspondence should be addressed.

Aging is characterized by a decrease of muscle mass associated with a decrease in postprandial anabolism. This study was performed to gain a better understanding of the intracellular mechanisms involved in the stimulation of muscle protein synthesis by amino acids and their role in the decrease of muscle sensitivity to food intake during aging. The effects of amino acids or leucine alone were assessed in vitro on epitrochlearis muscle from young, adult and old rats. Protein synthesis was assessed by incorporation of radiolabeled phenylalanine into protein and p70 S6 kinase activity by incorporation of ³²P into a synthetic substrate. Amino acids, at physiologic concentrations, stimulated muscle protein synthesis (P < 0.05) and leucine reproduced this effect. The intracellular targets of amino acids were phosphatidylinositol 3' kinase and the rapamycin-sensitive pathways mammalian target of rapamycin (mTOR)/p70 S6 kinase. In old rats, the sensitivity of muscle protein synthesis to leucine was lower than in adults (P < 0.05) and this paralleled the lesser ability of leucine to stimulate the rapamycin-sensitive pathways (P < 0.05). We demonstrated that amino acids and leucine stimulate muscle protein synthesis and that aging is associated with a decrease in this effect. However, because aged rats are still able to respond normally to high leucine concentrations, we hypothesize that a nutritional manipulation increasing the availability of this amino acid to muscle could be beneficial in maintaining the postprandial stimulation of protein synthesis.

KEY WORDS: • rats • protein synthesis • leucine • age • muscle

This article has been cited by other articles:

				E. L. Dillon, M. Sheffield-Moore, D. Paddon-Jones, C. Gilkison, A. P. Sanford, S. L. Casperson, J. Jiang, D. L. Chinkes, and R. J. Urban 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., May 1, 2009; 94(5): 1630 - 1637. [Abstract] [Full Text] [PDF]

				S. Verhoeven, K. Vanschoonbeek, L. B Verdijk, R. Koopman, W. K. Wodzig, P. Dendale, and L. J. van Loon Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men Am. J. Clinical Nutrition, May 1, 2009; 89(5): 1468 - 1475. [Abstract] [Full Text] [PDF]

				B. Marzani, M. Balage, A. Venien, T. Astruc, I. Papet, D. Dardevet, and L. Mosoni Antioxidant Supplementation Restores Defective Leucine Stimulation of Protein Synthesis in Skeletal Muscle from Old Rats J. Nutr., November 1, 2008; 138(11): 2205 - 2211. [Abstract] [Full Text] [PDF]

				D. Dardevet, S. R Kimball, L. S Jefferson, A. D Cherrington, D. Remond, C. A DiCostanzo, and M. C. Moore Portal infusion of amino acids is more efficient than peripheral infusion in stimulating liver protein synthesis at the same hepatic amino acid load in dogs Am. J. Clinical Nutrition, October 1, 2008; 88(4): 986 - 996. [Abstract] [Full Text] [PDF]

				D. Liu, E. J. Metter, L. Ferrucci, and S. M. Roth TNF promoter polymorphisms associated with muscle phenotypes in humans J Appl Physiol, September 1, 2008; 105(3): 859 - 867. [Abstract] [Full Text] [PDF]

				J. Escobar, J. W. Frank, A. Suryawan, H. V. Nguyen, and T. A. Davis Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1615 - E1621. [Abstract] [Full Text] [PDF]

				T. C. Vary and C. J. Lynch Nutrient Signaling Components Controlling Protein Synthesis in Striated Muscle J. Nutr., August 1, 2007; 137(8): 1835 - 1843. [Abstract] [Full Text] [PDF]

				C. Moinard and L. Cynober Citrulline: A New Player in the Control of Nitrogen Homeostasis J. Nutr., June 1, 2007; 137(6): 1621S - 1625S. [Abstract] [Full Text] [PDF]

				D. Remond, M. Machebeuf, C. Yven, C. Buffiere, L. Mioche, L. Mosoni, and P. P. Mirand Postprandial whole-body protein metabolism after a meat meal is influenced by chewing efficiency in elderly subjects Am. J. Clinical Nutrition, May 1, 2007; 85(5): 1286 - 1292. [Abstract] [Full Text] [PDF]

				M. Lacroix, C. Bos, J. Leonil, G. Airinei, C. Luengo, S. Dare, R. Benamouzig, H. Fouillet, J. Fauquant, D. Tome, et al. Compared with casein or total milk protein, digestion of milk soluble proteins is too rapid to sustain the anabolic postprandial amino acid requirement. Am. J. Clinical Nutrition, November 1, 2006; 84(5): 1070 - 1079. [Abstract] [Full Text] [PDF]

				I. Rieu, M. Balage, C. Sornet, C. Giraudet, E. Pujos, J. Grizard, L. Mosoni, and D. Dardevet Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia J. Physiol., August 15, 2006; 575(1): 305 - 315. [Abstract] [Full Text] [PDF]

				C. S. Katsanos, H. Kobayashi, M. Sheffield-Moore, A. Aarsland, and R. R. Wolfe 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, August 1, 2006; 291(2): E381 - E387. [Abstract] [Full Text] [PDF]

				D. M. Thomson and S. E. Gordon Impaired overload-induced muscle growth is associated with diminished translational signalling in aged rat fast-twitch skeletal muscle J. Physiol., July 1, 2006; 574(1): 291 - 305. [Abstract] [Full Text] [PDF]

				K. Funai, J. D. Parkington, S. Carambula, and R. A. Fielding Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R1080 - R1086. [Abstract] [Full Text] [PDF]

				S. Fujita and E. Volpi Amino Acids and Muscle Loss with Aging J. Nutr., January 1, 2006; 136(1): 277S - 280S. [Abstract] [Full Text] [PDF]

				L. Combaret, D. Dardevet, I. Rieu, M.-N. Pouch, D. Bechet, D. Taillandier, J. Grizard, and D. Attaix A leucine-supplemented diet restores the defective postprandial inhibition of proteasome-dependent proteolysis in aged rat skeletal muscle J. Physiol., December 1, 2005; 569(2): 489 - 499. [Abstract] [Full Text] [PDF]

				C. S Katsanos, H. Kobayashi, M. Sheffield-Moore, A. Aarsland, and R. R Wolfe Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids Am. J. Clinical Nutrition, November 1, 2005; 82(5): 1065 - 1073. [Abstract] [Full Text] [PDF]

				M. Prod'homme, M. Balage, E. Debras, M.-C. Farges, S. Kimball, L. Jefferson, and J. Grizard Differential effects of insulin and dietary amino acids on muscle protein synthesis in adult and old rats J. Physiol., February 15, 2005; 563(1): 235 - 248. [Abstract] [Full Text] [PDF]

				C. H. Lang and R. A. Frost Differential effect of sepsis on ability of leucine and IGF-I to stimulate muscle translation initiation Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E721 - E730. [Abstract] [Full Text] [PDF]

				J. D. Parkington, N. K. LeBrasseur, A. P. Siebert, and R. A. Fielding Contraction-mediated mTOR, p70S6k, and ERK1/2 phosphorylation in aged skeletal muscle J Appl Physiol, July 1, 2004; 97(1): 243 - 248. [Abstract] [Full Text] [PDF]

				M. Dangin, C. Guillet, C. Garcia-Rodenas, P. Gachon, C. Bouteloup-Demange, K. Reiffers-Magnani, J. Fauquant, O. Ballevre, and B. Beaufrere The rate of protein digestion affects protein gain differently during aging in humans J. Physiol., June 1, 2003; 549(2): 635 - 644. [Abstract] [Full Text] [PDF]

				I. Rieu, C. Sornet, G. Bayle, J. Prugnaud, C. Pouyet, M. Balage, I. Papet, J. Grizard, and D. Dardevet Leucine-Supplemented Meal Feeding for Ten Days Beneficially Affects Postprandial Muscle Protein Synthesis in Old Rats J. Nutr., April 1, 2003; 133(4): 1198 - 1205. [Abstract] [Full Text] [PDF]

				M. L. McDaniel, C. A. Marshall, K. L. Pappan, and G. Kwon Metabolic and Autocrine Regulation of the Mammalian Target of Rapamycin by Pancreatic {beta}-Cells Diabetes, October 1, 2002; 51(10): 2877 - 2885. [Abstract] [Full Text] [PDF]

				M. J. Rennie, J. Bohe, and R. R. Wolfe Latency, Duration and Dose Response Relationships of Amino Acid Effects on Human Muscle Protein Synthesis J. Nutr., October 1, 2002; 132(10): 3225S - 3227. [Abstract] [Full Text] [PDF]

				M.-A. Arnal, L. Mosoni, D. Dardevet, M.-C. Ribeyre, G. Bayle, J. Prugnaud, and P. Patureau Mirand Pulse Protein Feeding Pattern Restores Stimulation of Muscle Protein Synthesis during the Feeding Period in Old Rats J. Nutr., May 1, 2002; 132(5): 1002 - 1008. [Abstract] [Full Text] [PDF]

				D. Dardevet, C. Sornet, G. Bayle, J. Prugnaud, C. Pouyet, and J. Grizard Postprandial Stimulation of Muscle Protein Synthesis in Old Rats Can Be Restored by a Leucine-Supplemented Meal J. Nutr., January 1, 2002; 132(1): 95 - 100. [Abstract] [Full Text] [PDF]