Abstract
Many conditions that shift cells from states of nutrient utilization and growth to states of cell maintenance extend lifespan. We have carried out a systematic lifespan analysis of conditions that inhibit protein synthesis. We find that reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans. These perturbations, as well as inhibition of the nutrient sensor target of rapamycin (TOR), which is known to increase lifespan, all increase thermal-stress resistance. Thus inhibiting translation may extend lifespan by shifting cells to physiological states that favor maintenance and repair. Interestingly, different types of translation inhibition lead to one of two mutually exclusive outputs, one that increases lifespan and stress resistance through the transcription factor DAF-16/FOXO, and one that increases lifespan and stress resistance independently of DAF-16. Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Caloric Restriction
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Eukaryotic Initiation Factors / genetics
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Eukaryotic Initiation Factors / metabolism
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Forkhead Transcription Factors
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Gene Expression Regulation / genetics*
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Heat Stress Disorders / genetics
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Heat Stress Disorders / metabolism
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Longevity / genetics*
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Protein Biosynthesis / genetics*
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Protein Serine-Threonine Kinases
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Receptor, Insulin / genetics
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Receptor, Insulin / metabolism
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Ribosomal Protein S6 Kinases / genetics
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Ribosomal Protein S6 Kinases / metabolism
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Ribosomal Proteins / genetics
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Ribosomal Proteins / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Signal Transduction / physiology
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Survival Rate
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Caenorhabditis elegans Proteins
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Eukaryotic Initiation Factors
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Forkhead Transcription Factors
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Ribosomal Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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daf-16 protein, C elegans
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DAF-2 protein, C elegans
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Receptor, Insulin
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Protein Serine-Threonine Kinases
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Ribosomal Protein S6 Kinases
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target of rapamycin protein, S cerevisiae