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Aging impairs the activation of stress signaling pathways (SSPs), preventing the induction of longevity mechanisms late in life. Here, we show that the antibiotic minocycline increases lifespan and reduces protein aggregation even in old, SSP-deficient Caenorhabditis elegans by targeting cytoplasmic ribosomes, preferentially attenuating translation of highly translated mRNAs. In contrast to most other longevity paradigms, minocycline inhibits rather than activates all major SSPs and extends lifespan in mutants deficient in the activation of SSPs, lysosomal or autophagic pathways. We propose that minocycline lowers the concentration of newly synthesized aggregation-prone proteins, resulting in a relative increase in protein-folding capacity without the necessity to induce protein-folding pathways. Our study suggests that in old individuals with incapacitated SSPs or autophagic pathways, pharmacological attenuation of cytoplasmic translation is a promising strategy to reduce protein aggregation. Altogether, it provides a geroprotecive mechanism for the many beneficial effects of tetracyclines in models of neurodegenerative disease.
Pubmed ID: 30479271 RIS Download
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View all literature mentionsCollection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
View all literature mentionsScientists at the Yates Lab at The Scripps Research Institute (TSRI) rely on information yielded by tandem mass spectrometry to identify proteins from complex mixtures. Using this powerful technique, researchers draw upon a cross section of fields to increase the scope, sensitivity, and throughput of technologies for practical proteomics. Biologists provide the questions that drive our research. By identifying complexes that are poorly understood or organism-wide issues requiring further exploration, we gain a theoretical understanding of issues that are tractable only through proteomic strategies. Analytical chemists and biochemists improve our tools for revealing the proteins present in biological samples. Targets for optimization include the isolations used to obtain proteins, the steps to generate peptides from these proteins, and the separation of peptides en route to the mass spectrometer. Chemistry is vital to increasing power of proteomic technology. Computer science yields tools on two scales. First, the sequence corresponding to each peptide''s tandem mass spectrum must be identified. Once those identifications have been completed, additional tools are needed to summarize and organize these identifications.
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View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsCaenorhabditis elegans with name xbp-1(zc12) III; zcIs4 V. from WB.
View all literature mentionsCaenorhabditis elegans with name rsks-1(ok1255) III. from WB.
View all literature mentionsCaenorhabditis elegans with name wuIs152 [sod-1 gDNA rol-6(su1006)]; hsf-1(sy441) I from WB.
View all literature mentionsCaenorhabditis elegans with name rsks-1(ok1255) III. from WB.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets HSP70/HSP72 mAb (C92F3A-5)
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets HSPA5
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Actin
View all literature mentionsThis monoclonal targets HSP60
View all literature mentionsSoftware for automatic general image analysis. It provides fully automatic analysis of 1-D gels including lane creation, background subtraction, band detection, molecular weight calibration, quantity calibration, and normalization. Editing tools are provided for cropping, rotating, and filtering images.
View all literature mentionsCaenorhabditis elegans with name xbp-1(zc12) III; zcIs4 V. from WB.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCaenorhabditis elegans with name rsks-1(ok1255) III. from WB.
View all literature mentionsCaenorhabditis elegans with name skn-1(zj15) IV. from WB.
View all literature mentionsSoftware tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.
View all literature mentionsCaenorhabditis elegans with name pkIs2386 [unc-54p::alpha-synnuclein::YFP + unc-119(+)] from WB.
View all literature mentionsCaenorhabditis elegans with name zcIs13 V. from WB.
View all literature mentionsCaenorhabditis elegans with name ncl-1(e1865) III. from WB.
View all literature mentionsCaenorhabditis elegans with name xbp-1(zc12) III; zcIs4 V. from WB.
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCaenorhabditis elegans with name skn-1(zj15) IV. from WB.
View all literature mentionsCaenorhabditis elegans with name zcIs13 V. from WB.
View all literature mentionsSoftware for automatic general image analysis. It provides fully automatic analysis of 1-D gels including lane creation, background subtraction, band detection, molecular weight calibration, quantity calibration, and normalization. Editing tools are provided for cropping, rotating, and filtering images.
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets HSPA5
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsSoftware tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis monoclonal targets Actin
View all literature mentionsThis monoclonal targets HSP70/HSP72 mAb (C92F3A-5)
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