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

Ivana Bjedov, Janne M. Toivonen, Fiona Kerr, Cathy Slack, Jake Jacobson, Andrea Foley, Linda Partridge

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages35-46
Number of pages12
JournalCell metabolism
Volume11
Issue number1
Early online date5 Jan 2010
DOIs
Publication statusPublished - 6 Jan 2010

Fingerprint

Sirolimus
Life Expectancy
Drosophila melanogaster
Diptera
Fruit
Paraquat
Autophagy
Starvation
Pharmaceutical Preparations
Drosophila
Mammals
Phosphotransferases
Down-Regulation
Insulin
Food

Bibliographical note

Open access under CC BY license.

Keywords

  • humdisease
  • proteins chemistry

Cite this

Bjedov, I., Toivonen, J. M., Kerr, F., Slack, C., Jacobson, J., Foley, A., & Partridge, L. (2010). Mechanisms of life span extension by rapamycin in the fruit fly drosophila melanogaster. 11(1), 35-46. https://doi.org/10.1016/j.cmet.2009.11.010
Bjedov, Ivana ; Toivonen, Janne M. ; Kerr, Fiona ; Slack, Cathy ; Jacobson, Jake ; Foley, Andrea ; Partridge, Linda. / Mechanisms of life span extension by rapamycin in the fruit fly drosophila melanogaster. 2010 ; Vol. 11, No. 1. pp. 35-46.
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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' vol. 11, no. 1, pp. 35-46. https://doi.org/10.1016/j.cmet.2009.11.010

Mechanisms of life span extension by rapamycin in the fruit fly drosophila melanogaster. / Bjedov, Ivana; Toivonen, Janne M.; Kerr, Fiona; Slack, Cathy; Jacobson, Jake; Foley, Andrea; Partridge, Linda.

Vol. 11, No. 1, 06.01.2010, p. 35-46.

Research output: Contribution to journalArticle

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