Accelerated aging of Asp 58 in αA crystallin and human cataract formation

Racemisation of amino acids is one of the most abundant modifications in long-lived proteins. In this study racemisation of Asp 58 in the small heat shock protein, αA crystallin, was investigated. In normal human lenses, levels of l-isoAsp, d-isoAsp and d-Asp increased with age, such that by age 70 they accounted for approximately half of the total Asp at this site. Levels of d-isoAsp were significantly higher in all cataract lenses than age-matched normal lenses. The introduction of d-isoAsp in αA crystallin could therefore be associated with the development of cataract. Its more rapid formation in cataract lenses may represent an example of accelerated protein aging leading to a human age-related disease.