The ultimate goal of the prospective studies is to understand the nature of the mechanisms underlying the aging process in animals. The objective of the proposed studies is to test the predictions of the free radical hypothesis of aging. The relationship between rates of oxy-radical generation and aging will be explored by pursuing three different lives of investigation: (1) Determine if rates of O2 and H2O2 generation by mitochondria increase during aging in mammalian and insect species. (2) Determine if rates of O2 and H2O2 generation by mitochondria are correlated with variations in life span of different mammalian and insect species. Comparisons will be made within rather than between the phylogenetic groups. (3) Investigate why the rates of O2 and H2O2 generation by mitochondria vary in different tissues and species. Results of this study will promote a better understanding of the relationship between oxy-radical and hydroperoxide production by mitochondria and the aging process.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG007657-06
Application #
2049847
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1988-08-01
Project End
1995-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Southern Methodist University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75205
Sohal, Rajindar S; Forster, Michael J (2014) Caloric restriction and the aging process: a critique. Free Radic Biol Med 73:366-82
Klichko, Vladimir; Sohal, Barbara H; Radyuk, Svetlana N et al. (2014) Decrease in cytochrome c oxidase reserve capacity diminishes robustness of Drosophila melanogaster and shortens lifespan. Biochem J 459:127-35
Orr, William C; Radyuk, Svetlana N; Sohal, Rajindar S (2013) Involvement of redox state in the aging of Drosophila melanogaster. Antioxid Redox Signal 19:788-803
Sohal, Rajindar S; Orr, William C (2012) The redox stress hypothesis of aging. Free Radic Biol Med 52:539-555
Ren, Jian-Ching; Rebrin, Igor; Klichko, Vladimir et al. (2010) Cytochrome c oxidase loses catalytic activity and structural integrity during the aging process in Drosophila melanogaster. Biochem Biophys Res Commun 401:64-8
Mockett, Robin J; Sohal, Barbara H; Sohal, Rajindar S (2010) Expression of multiple copies of mitochondrially targeted catalase or genomic Mn superoxide dismutase transgenes does not extend the life span of Drosophila melanogaster. Free Radic Biol Med 49:2028-31
Radyuk, Svetlana N; Michalak, Katarzyna; Klichko, Vladimir I et al. (2009) Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila. Biochem J 419:437-45
Sohal, Rajindar S; Toroser, Dikran; Bregere, Catherine et al. (2008) Age-related decrease in expression of mitochondrial DNA encoded subunits of cytochrome c oxidase in Drosophila melanogaster. Mech Ageing Dev 129:558-61
Rebrin, Igor; Sohal, Rajindar S (2008) Pro-oxidant shift in glutathione redox state during aging. Adv Drug Deliv Rev 60:1545-52
Toroser, Dikran; Orr, William C; Sohal, Rajindar S (2007) Carbonylation of mitochondrial proteins in Drosophila melanogaster during aging. Biochem Biophys Res Commun 363:418-24

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