An involvement of mitochondria in aging processes has often been proposed. Mitochondrial function declines with age and this may bring serious negative outcomes. There is increasing evidence for an association of mitochondrial DNA (mtDNA) deletions with age. These mtDNA deletions appear 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 male and female rhesus monkeys. We are guided by the hypothesis (see figure) that mtDNA abnormalities 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 (ETS) and oxidative phosphorylation (OXPHOS). The study of DR is motivated by extensive recent evidence that it reduces free radical damage in aging rodents. We view the mitochondrial genome as one which is critical to lifespan potential because it is highly vulnerable to damage and encodes for physiologically essential proteins. In order to clarify the possible importance of age-related mtDNA abnormalities, we propose to accomplish three Specific Aims: #1) To complete the sequencing of the rhesus monkey mitochondrial genome. #2) To characterize the influences of aging and DR on mtDNA abnormalities (deletions, oxidatively damaged bases). #3) To characterize the activities of enzymes involved in ETS, OXPHOS and free radical detoxification. These studies should provide critical data for determining the relationship among mtDNA abnormalities, mitochondrial function, and the rate of aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
1P01AG011915-01A1
Application #
3746361
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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