Molecular aging of lens crystallins and the life expectancy of the animal. Age-related protein structural changes studied in situ by Raman spectroscopy.

In order to investigate the relationship of molecular aging of lens crystallins to an animal's life expectancy or to the type of the lens, Raman spectra have been measured in situ for rabbit and guinea-pig lens nuclei at various stages of aging; these spectra have been compared with those of rat and mouse lens nuclei previously reported. Lens aging results in pronounced differences among the Raman spectra of the lens nuclei of the four species. It is shown that the rates of dehydration, inter- and intramolecular disulfide bond formation, and microenvironmental changes in the tryptophan residues of lens crystallins are different among the four species. Much faster changes occur for rat and mouse, which have a shorter life expectancy (2 years) and give rise to hard lens nuclei while slower changes occur for rabbit and guinea-pig, which have a longer life expectancy (5-7 years), and give soft lens nuclei. In addition, the Raman data reveal, for all the species investigated, that there are correlations among the rates of the dehydration, the inter- and intramolecular disulfide bond formation, and the microenvironmental changes in the tryptophan residues. Therefore, there seems to be a common mechanism for molecular aging of lens crystallins among the four species, although the rate of the molecular aging strongly depends upon the life expectancy of the animal and the type of the lens. The most important factor determining the rate of the molecular aging is probably the dehydration which decreases free water in the lens nucleus.