PMID- 11053498 OWN - NLM STAT- MEDLINE DCOM- 20001208 LR - 20240109 IS - 0022-3166 (Print) IS - 0022-3166 (Linking) VI - 130 IP - 11 DP - 2000 Nov TI - Stimulation of in vitro rat muscle protein synthesis by leucine decreases with age. PG - 2630-5 AB - 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 (32)P 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. FAU - Dardevet, D AU - Dardevet D AD - Human Nutrition Research Center of Clermont-Ferrand and Institut National de la Recherche Agronomique, Unite d'Etude du Metabolisme Azote, 63122 Ceyrat, France. FAU - Sornet, C AU - Sornet C FAU - Balage, M AU - Balage M FAU - Grizard, J AU - Grizard J LA - eng PT - Journal Article PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (Amino Acids) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Immunosuppressive Agents) RN - 0 (Morpholines) RN - 0 (Muscle Proteins) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - GMW67QNF9C (Leucine) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Aging/*metabolism MH - Amino Acids/metabolism/pharmacology MH - Animals MH - Chromones/pharmacology MH - Enzyme Inhibitors/pharmacology MH - Flavonoids/pharmacology MH - Immunosuppressive Agents/pharmacology MH - Leucine/*metabolism/pharmacology MH - Male MH - Morpholines/pharmacology MH - Muscle Proteins/*biosynthesis/drug effects MH - Phosphoinositide-3 Kinase Inhibitors MH - Rats MH - Rats, Wistar MH - Sirolimus/pharmacology EDAT- 2000/10/29 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/29 11:00 PHST- 2000/10/29 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/29 11:00 [entrez] AID - 10.1093/jn/130.11.2630 [doi] PST - ppublish SO - J Nutr. 2000 Nov;130(11):2630-5. doi: 10.1093/jn/130.11.2630.