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Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster

Title: Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster
Authors: Bjedov, I; Toivonen, JM; Kerr, F; Slack, C; Jacobson, J; Foley, A; Partridge, L
Source: Cell Metabolism , 11 (1) 35 - 46. (2010)
Publisher Information: CELL PRESS
Publication Year: 2010
Collection: University College London: UCL Discovery
Subject Terms: s6 kinase; caenorhabditis-elegans; dietary restriction; autophagy genes; c-elegans; insulin-resistance; stress resistance; adult drosophila; cell-survival; growth
Description: 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/lgf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/141359/
Availability: https://discovery.ucl.ac.uk/id/eprint/141359/1/1-s2.0-S155041310900374X-main.pdf; https://discovery.ucl.ac.uk/id/eprint/141359/
Rights: open
Accession Number: edsbas.D67515C0
Database: BASE