Abstract

To begin to understand the biology of aging, we propose to identify genes which are differentially expressed during aging, and determine the mechanisms for this regulation. The heat shock protein 70 (hsp7O) gene was found to be induced in muscle during aging, and using transgenic flies, this induction was found to require previously unidentified promoter elements. These same novel elements may also mediate hsp7O induction by oxygen radicals. We propose to analyze in detail the promoter sequences and trans-acting factors which regulate aging-specific hsp7O expression, and their possible relationship to oxygen radical production. To identify additional genes with aging-specific expression patterns, we have analyzed 600 fly lines containing genetically engineered transposons called """"""""enhancer-traps"""""""", which act as reporters for the expression patterns of genes. 12 lines exhibit various aging- and tissue-specific expression patterns. The genes identified by several of these enhancer- traps will be identified, cloned and analyzed, with the goal of understanding the mechanisms for tissue-specific changes in gene expression during aging.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG011833-04
Application #
2001517
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Finkelstein, David B
Project Start
1993-12-01
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
4
Fiscal Year
1997
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

Pomatto, Laura C D; Tower, John; Davies, Kelvin J A (2018) Sexual Dimorphism and Aging Differentially Regulate Adaptive Homeostasis. J Gerontol A Biol Sci Med Sci 73:141-149
Pomatto, Laura C D; Wong, Sarah; Tower, John et al. (2018) Sex-specific adaptive homeostasis in D. melanogaster depends on increased proteolysis by the 20S Proteasome: Data-in-Brief. Data Brief 17:653-661
Tower, John; Landis, Gary N; Shen, Jie et al. (2017) Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life span-shortening and pro-inflammatory effects of male Sex Peptide. Biogerontology 18:413-427
Pomatto, Laura C D; Wong, Sarah; Carney, Caroline et al. (2017) The age- and sex-specific decline of the 20s proteasome and the Nrf2/CncC signal transduction pathway in adaption and resistance to oxidative stress in Drosophila melanogaster. Aging (Albany NY) 9:1153-1185
Shen, Jie; Landis, Gary N; Tower, John (2017) Multiple Metazoan Life-span Interventions Exhibit a Sex-specific Strehler-Mildvan Inverse Relationship Between Initial Mortality Rate and Age-dependent Mortality Rate Acceleration. J Gerontol A Biol Sci Med Sci 72:44-53
Tower, John (2017) Sex-Specific Gene Expression and Life Span Regulation. Trends Endocrinol Metab 28:735-747
Pomatto, Laura C D; Wong, Sarah; Tower, John et al. (2017) Sexual dimorphism in oxidant-induced adaptive homeostasis in multiple wild-type D. melanogaster strains. Arch Biochem Biophys 636:57-70
Pomatto, Laura C D; Carney, Caroline; Shen, Brenda et al. (2017) The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress. Curr Biol 27:1-15
Fear, Justin M; León-Novelo, Luis G; Morse, Alison M et al. (2016) Buffering of Genetic Regulatory Networks in Drosophila melanogaster. Genetics 203:1177-90
Tower, John (2015) Programmed cell death in aging. Ageing Res Rev 23:90-100

Showing the most recent 10 out of 56 publications