Aging, physical activity, and cardiac apoptosis

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DESCRIPTION (provided by applicant): One's physical activity level is known to decrease with age. This decrement in activity has been shown to be associated with age-associated health concerns, i.e., obesity, diabetes, and cardiovascular disease. Recent research in our laboratory has shown a genetic influence in the age-associated change in physical activity patterns. Therefore, this research study will study the genetic influence on physical activity level during the aging process. In addition, we will investigate the relationship of physical activity and cardiac cell death in aging mice. This project will be the first to determine the influence of genetics on the age-related decline in physical activity level, as well as the relationship between the age-related changes in physical activity and cardiac apoptosis in inbred mice. One hundred ninety mice (male and female) will be studied. Initially we will breed our progenitor strains (DBA/2J x SWR/J) to generate our F1 (20 mice). After a brief period to phenotype our F1 population, we will generate backcross mice (40 mice) to allow for segregation analysis. Lastly, F2 (130 mice) will be produced for the performance of segregation and linkage analysis. Our pilot research has found these inbred strains to possess differing age-related changes in physical activity patterns. All mice will be housed separately (at age 6 weeks) in a cage with a suspended running wheel to measure the daily distance traveled and duration of activity. At specific time points (10 mice at ages 6 weeks, 26 weeks, and 39 weeks), F2 mice will be randomly selected to be sacrificed for the genetic analysis and measurement of cardiac apoptosis. Additionally, at one year of age, all F1, backcross, and remaining F2 mice will be sacrificed for genetic analysis and measurement of cardiac apoptosis. The spleen, lungs, and kidneys will be removed for the separation of RNA for linkage analysis. The hearts will be removed with portions of the left and right ventricles fixed for later determination of apoptosis activity by TUNEL assay and DNA laddering. We hypothesize: 1) a polygenic influence on the age-related decrease in physical activity and 2) a significant relationship between the changes in age-associated physical activity level and amount of cardiac apoptosis. The information gathered from these studies will provide the foundation for future studies whose purpose will be to further delineate the location and specific genetic control of physical activity with aging.