期刊
AGING CELL
卷 12, 期 5, 页码 742-751出版社
WILEY
DOI: 10.1111/acel.12101
关键词
Caenorhabditis elegans; general control nonderepressible 2; target of rapamycin; PHA-4; aging
资金
- European Research Council [201975]
- National Institutes for Health National Center for Research Resources (Minneapolis)
- European Research Council (ERC) [201975] Funding Source: European Research Council (ERC)
Summary The general control nonderepressible 2 (GCN2) kinase is a nutrient-sensing pathway that responds to amino acids deficiency and induces a genetic program to effectively maintain cellular homeostasis. Here we established the conserved role of Caenorhabditis elegans GCN-2 under amino acid limitation as a translation initiation factor 2 (eIF2) kinase. Using a combination of genetic and molecular approaches, we showed that GCN-2 kinase activity plays a central role in survival under nutrient stress and mediates lifespan extension conferred by dietary restriction (DR) or inhibition of the major nutrient-sensing pathway, the target of rapamycin (TOR). We also demonstrated that the GCN-2 and TOR signaling pathways converge on the PHA-4/FoxA transcription factor and its downstream target genes to ensure survival of the whole organism under a multitude of stress conditions, such as nutrient scarcity or environmental stresses. This is one step forward in the understanding of evolutionary conserved mechanisms that confer longevity and healthspan.
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