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PMID: 20074526 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster.

Cell metabolism ·Vol. 11 ·No. 1 ·2010-01-00 ·Pages 35-46

Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L

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/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.

MeSH Terms
Aging/physiology Animals Autophagy Drosophila Proteins/metabolism Drosophila melanogaster/physiology Longevity Phosphorylation Protein Biosynthesis/drug effects Protein Kinases/metabolism Proto-Oncogene Proteins c-akt/metabolism Ribosomal Protein S6 Kinases/metabolism Sirolimus/pharmacology TOR Serine-Threonine Kinases
Chemicals
Drosophila Proteins Protein Kinases target of rapamycin protein, Drosophila Proto-Oncogene Proteins c-akt Ribosomal Protein S6 Kinases TOR Serine-Threonine Kinases Sirolimus
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bjedov Ivana
Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, UK.
Toivonen Janne M
Kerr Fiona
Slack Cathy
Jacobson Jake
Foley Andrea
Partridge Linda
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Article Info
Journal
Cell metabolism
Abbr.
Cell Metab
ISSN
1932-7420
DOI
10.1016/j.cmet.2009.11.010
Published
2010-01-00
Pages
35-46
Language
English
Region
United States
NLM ID
101233170
PMCID
PMC2824086
Subset
IM
External Links
PubMed source DOI: 10.1016/j.cmet.2009.11.010 PMC Full Text View journal details
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