Document Detail


Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR.
MedLine Citation:
PMID:  23216249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.
Authors:
Jordan Gallinetti; Eylul Harputlugil; James R Mitchell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  The Biochemical journal     Volume:  449     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-02-08     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-10     Citation Subset:  IM    
Affiliation:
Department of Genetics and Complex Diseases, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, U.S.A.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / physiology*
Animals
Caloric Restriction* / methods
Humans
Longevity / physiology*
Protein Binding / physiology
Protein-Serine-Threonine Kinases / physiology*
Signal Transduction / physiology*
TOR Serine-Threonine Kinases / physiology*
Grant Support
ID/Acronym/Agency:
AG036712/AG/NIA NIH HHS; DK090629/DK/NIDDK NIH HHS; R01 AG036712/AG/NIA NIH HHS; R01 DK090629/DK/NIDDK NIH HHS; T32 ES016645/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/EIF2AK4 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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