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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

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