Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster
| Autor: | Cathy Slack, Jake Jacobson, Janne M. Toivonen, Fiona Kerr, Linda Partridge, Andrea Foley, Ivana Bjedov |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
572 Biochemistry
Aging Physiology PROTEINS media_common.quotation_subject Longevity HUMDISEASE Article 03 medical and health sciences 0302 clinical medicine Humdisease proteins Autophagy Animals Drosophila Proteins Phosphorylation Molecular Biology Caenorhabditis elegans 030304 developmental biology media_common 2. Zero hunger Genetics Sirolimus 0303 health sciences biology Ribosomal Protein S6 Kinases TOR Serine-Threonine Kinases Translation (biology) QR Microbiology Cell Biology biology.organism_classification 3. Good health Cell biology Drosophila melanogaster Protein Biosynthesis Protein Kinases Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Drosophila Protein |
| Zdroj: | Cell Metabolism Cell Metab |
| ISSN: | 1932-7420 1550-4131 |
| Popis: | Summary The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation. Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms. Highlights ► Rapamycin, a drug that inhibits TOR pathway, improves longevity in Drosophila ► Rapamycin longevity effects are mediated through the TOR pathway ► Life span extension by rapamycin is through translation changes and autophagy ► Rapamycin extends life span beyond dietary restriction and mild IIS mutations |
| Databáze: | OpenAIRE |
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