Dietary restriction (DR) is defined as a 25-50% decrease in calorie intake without a decrease in essential nutrients. Such undernutrition without malnutrition 1) increases average and maximal survival times of rodents, 2) prolongs aspects of normal organ function, and 3) delays the onset of several late life diseases. For example, it has been observed that 11 month old lenses of mice on restricted diets show enhanced solubility of gamma crystallins as compared with normally fed age matched control animals. This is significant since insolubization of damaged or altered crystallins (particularly gamma) is associated with lens aging and cataractogenesis in many species including humans. It is the objective of this research to determine if dietary restricted mice have delayed onset- or diminished incidence of cataract. In order to pursue these studies we will use the Emory mouse since in chronology of development, patterns of protein aggregation, and histological appearance, Emory cataracts resemble human senile cataract. Furthermore 100% of mice in our colony are expected to develop cataract in less than a year. It is generally agreed that altered proteins are more rapidly degraded than native proteins by cellular proteases. Recent work from this laboratory demonstrated that with increasing age the lens proteases are inactivated. It is plausable that this decrement in proteolytic capability results in the accumulation and eventual precipitation in cataractous opacities of damaged lens proteins. By comparison of the incidence of cataract in DR groups of Emory and CFW (control) mice with normally fed mice we will ascertain the effect of DR on lens function. Furthermore by analysis of protein profiles and endo- and exoprotease activities before, at the time of, and subsequent to the onset of cataract, we will determine if protease inactivation is preceeded by, is synchronous with, or follows age related protease inactivation.
