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Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway

Kapahi, Pankaj and Zid, Brian M. and Harper, Tony and Koslover, Daniel and Sapin, Viveca and Benzer, Seymour (2004) Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway. Current Biology, 14 (10). pp. 885-890. ISSN 0960-9822. PMCID PMC2754830. doi:10.1016/j.cub.2004.03.059.

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In many species, reducing nutrient intake without causing malnutrition extends lifespan 1, 2, 3. Like DR (dietary restriction), modulation of genes in the insulin-signaling pathway, known to alter nutrient sensing, has been shown to extend lifespan in various species 1, 2, 3, 4. In Drosophila, the target of rapamycin (TOR) and the insulin pathways have emerged as major regulators of growth and size. Hence we examined the role of TOR pathway genes in regulating lifespan by using Drosophila. We show that inhibition of TOR signaling pathway by alteration of the expression of genes in this nutrient-sensing pathway, which is conserved from yeast to human, extends lifespan in a manner that may overlap with known effects of dietary restriction on longevity. In Drosophila, TSC1 and TSC2 (tuberous sclerosis complex genes 1 and 2) act together to inhibit TOR (target of rapamycin), which mediates a signaling pathway that couples amino acid availability to S6 kinase, translation initiation, and growth [5]. We find that overexpression of dTsc1, dTsc2, or dominant-negative forms of dTOR or dS6K all cause lifespan extension. Modulation of expression in the fat is sufficient for the lifespan-extension effects. The lifespan extensions are dependent on nutritional condition, suggesting a possible link between the TOR pathway and dietary restriction.

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Additional Information:© 2004 Cell Press. Published by Elsevier Ltd. Received 18 February 2004, Revised 22 March 2004, Accepted 22 March 2004, Available online 10 June 2004. We thank members of the Benzer laboratory, including G. Carvalho, D. Walker, E. Fabrikant, T. Brummel, D. Tracey, and H. Dar Wang for helpful discussions and comments on the manuscript. We also thank D. Pan, T. Neufeld, and M. Stewart for generously providing us with fly strains. This work was supported by a grant from the American Federation for Aging Research and a postdoctoral fellowship from the John Douglas French Alzheimer's Foundation Research to P.K., a California Institute of Technology SURF scholarship to D.K., and grants to S.B. from the National Institutes of Health (AG16630), the National Science Foundation (MCB-9907939), and the Ellison foundation.
Funding AgencyGrant Number
American Federation for Aging ResearchUNSPECIFIED
John Douglas French Alzheimer’s FoundationUNSPECIFIED
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
Ellison Medical FoundationUNSPECIFIED
Issue or Number:10
PubMed Central ID:PMC2754830
Record Number:CaltechAUTHORS:20190227-094730941
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Official Citation:Pankaj Kapahi, Brian M Zid, Tony Harper, Daniel Koslover, Viveca Sapin, Seymour Benzer, Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway, Current Biology, Volume 14, Issue 10, 2004, Pages 885-890, ISSN 0960-9822, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:93294
Deposited By: Tony Diaz
Deposited On:27 Feb 2019 17:58
Last Modified:16 Nov 2021 16:56

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