An involvement of mitochondria in aging processes has often been proposed. Mitochondrial function declines with age and this may have serious negative outcomes. There is increasing evidence for an association of mitochondrial DNA (mtDNA) deletions with age. These age-associated deletions appear to be most pronounced in nerve and muscle and hold great promise for explaining the major diseases and disorders old age brings to these tissues. We are proposing to study mtDNA abnormalities and associated outcomes with respect to age and life span-prolonging dietary restriction (DR) in mice. We are guided by the hypothesis that mtDNA abnormalities can trigger a broad continuum of biochemical outcomes and clinical symptoms. The mtDNA mutations and deletions result in decreases in the activity of the electron transport system (BTS) and oxidative phosphorylation (OXPHOS). The study of DR is motivated by extensive recent evidence that it reduces free radical damage in aging rodents. In order to clarify the possible importance of age-related mtDNA abnormalities, we propose to accomplish four Specific Aims: #1) to characterize age-associated mtDNA deletions in selected tissues in the mouse, #2) to quantify the abundance of mtDNA abnormalities in individual cells and muscle fibers, #3) to determine ETS activity levels and characterize age-associated changes in cellular morphology, and, #4) to determine the effect of DR on age-associated mtDNA abnormalities and ETS activities in the mouse. These studies should provide critical data for determining the relationship among mtDNA abnormalities, mitochondrial function, and the rate of aging. Studying this animal model in the context of age-related mitochondrial dysfunction should provide a system in which therapeutic interventions aimed at protecting mtDNA can be developed and evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG011604-03
Application #
2442273
Study Section
Nutrition Study Section (NTN)
Program Officer
Finkelstein, David B
Project Start
1995-07-10
Project End
1998-11-30
Budget Start
1997-07-15
Budget End
1998-11-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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