A progressive decline is physiological processes occurs in all organisms. A popular theory to explain this decline involves oxidative stress and subsequent damage to DNA, proteins and lipids. Delaying this decline is associated with extended lifespan. Mice with hereditary dwarfism (Ames dwarf, df/df) exhibit both delayed aging, living more than a year longer than normal siblings (P is less than 0.0001) and differences in antioxidant defense capacity. The objectives of this pilot project are to examine oxidative mechanisms in this mouse model and show that Ames dwarf mice are able to resist oxidative stress resulting in less oxidative damage and delayed aging.
The aims of this proposal are: 1) to examine levels of activity (protein, kinetics, mRNA) of enzymes involved in cellular oxidation/recycling (catalase and superoxide dismutase) in tissues from long-living dwarf and normal sibling mice at 3,6,12, 18 and 24 months of age; 2) to evaluate the cellular oxidative response to in vitro oxidative stress in hepatocytes from both groups of mice; and 3) to measure oxidative damage to DNA, proteins and lipids in dwarf and normal mice at different ages. The overall hypothesis is that the Ames dwarf mouse has a biologic advantage over normals with better enzymatic scavenging of toxic metabolic byproducts underlying their enhanced longevity. These studies will generate preliminary data, support earlier observations and further the understanding of the relationship between cellular oxidation and aging in a mammalian model of extended lifespan. The dwarf mutant may be a unique example of a 'gerontogene' in mammalian species. The information gleaned from these preliminary studies will further establish the dwarf as a genetic model of delayed aging and second, may substantiate the dwarf gene as a longevity determinant gene.
| Brown-Borg, H M; Rakoczy, S G (2000) Catalase expression in delayed and premature aging mouse models. Exp Gerontol 35:199-212 |
