The major objective of this proposal is to study the aging of mammalian lens with particular emphasis upon human material. It is hoped that such studies will assist in understanding why cataract is predominantly found in older individuals. The following specific aims have been selected on the basis of recent biochemical observations upon normal and cataractous material which appear to be particularly relevant to aging and its relationship to cataract. 1. Examination of the effect of aging upon the lens fiber membrane. This work will include nearest neighbor studies, investigation of the oxidation of membrane components including Na+/K+ ATPase, membrane fluidity, methionine sulfoxide reductase, and proteolysis. 2. Effect of aging upon protein synthesis. 3. Proteolysis and its contribution to the accumulation of age dependent degradation products. 4. Investigation of the age dependent generation of non-tryptophan fluorescence. 5. Examination ofthe water insoluble protein which accumulates with age in the normal lenses. 6. Investigation of the mechanisms causing the age dependent apparent racemization of L-aspartic acid. Biochemical, immunochemical, physiological and physical chemical techniques will be employed.
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