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

Bjedov, I; Toivonen, JM; Kerr, F; Slack, C; Jacobson, J; Foley, A; Partridge, L; (2010) Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster. Cell Metabolism , 11 (1) 35 - 46. 10.1016/j.cmet.2009.11.010. Green open access

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Abstract

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.

Type: Article
Title: Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cmet.2009.11.010
Publisher version: http://dx.doi.org/10.1016/j.cmet.2009.11.010
Language: English
Additional information: An Open Access Elsevier publication.
Keywords: s6 kinase, caenorhabditis-elegans, dietary restriction, autophagy genes, c-elegans, insulin-resistance, stress resistance, adult drosophila, cell-survival, growth
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/141359
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