Abstract

The long term goal of this project is to identify genes which directly affect human aging and health span, called Longevity Assurance Genes (LAGs). The fruit fly Drosophila melanogaster is used as a model organism for identifying LAGs because of its short life span, ease of culture, and the many genetic and molecular tools which can be applied to its study. The similarities between aging in Drosophila and humans at the cellular and molecular level suggest that LAGs identified in Drosophila may have functional homologs. 7 candidate LAGs were selected from known Drosophila genes based on several criteria. The genes are involved are involved in stress responses, DNA repair and energy storage, and each has known functional homologs in humans. The genes will be tested for effects on Drosophila life span by experimentally increasing and decreasing their activity in transgenic flies. In addition, genetic screens will be performed to identify novel Drosophila LAGs. These screens will utilize a newly-developed P-type transposable element as a mutagen, called PdL. PdL creates dominant conditional mutations, which should greatly facilitate the identification, characterization and cloning of novel Drosophila LAGs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG011644-06
Application #
2825857
Study Section
Special Emphasis Panel (ZAG1-PKN-2 (J1))
Program Officer
Mccormick, Anna M
Project Start
1993-09-01
Project End
2003-11-30
Budget Start
1999-04-01
Budget End
1999-11-30
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Southern California
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089

  Publications

Curtis, Christina; Landis, Gary N; Folk, Donna et al. (2007) Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes. Genome Biol 8:R262
Tower, John (2006) Sex-specific regulation of aging and apoptosis. Mech Ageing Dev 127:705-18
Landis, Gary N; Tower, John (2005) Superoxide dismutase evolution and life span regulation. Mech Ageing Dev 126:365-79
Bhole, Deepak; Allikian, Michael J; Tower, John (2004) Doxycycline-regulated over-expression of hsp22 has negative effects on stress resistance and life span in adult Drosophila melanogaster. Mech Ageing Dev 125:651-63
Landis, Gary N; Abdueva, Diana; Skvortsov, Dmitriy et al. (2004) Similar gene expression patterns characterize aging and oxidative stress in Drosophila melanogaster. Proc Natl Acad Sci U S A 101:7663-8
Phelan, John P; Archer, Margaret A; Beckman, Kelly A et al. (2003) Breakdown in correlations during laboratory evolution. I. Comparative analyses of Drosophila populations. Evolution 57:527-35
Archer, Margaret A; Phelan, John P; Beckman, Kelly A et al. (2003) Breakdown in correlations during laboratory evolution. II. Selection on stress resistance in Drosophila populations. Evolution 57:536-43
Landis, Gary N; Bhole, Deepak; Tower, John (2003) A search for doxycycline-dependent mutations that increase Drosophila melanogaster life span identifies the VhaSFD, Sugar baby, filamin, fwd and Cctl genes. Genome Biol 4:R8
Sun, Jingtao; Folk, Donna; Bradley, Timothy J et al. (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics 161:661-72
Allikian, Michael J; Deckert-Cruz, Denise; Rose, Michael R et al. (2002) Doxycycline-induced expression of sense and inverted-repeat constructs modulates phosphogluconate mutase (Pgm) gene expression in adult Drosophila melanogaster. Genome Biol 3:research0021

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