title: The etiology of human age-related cataract. Proteins don't last forever.
abstract: BACKGROUND
  It is probable that the great majority of human cataract results from the spontaneous decomposition of long-lived macromolecules in the human lens. Breakdown/reaction of long-lived proteins is of primary importance and recent proteomic analysis has enabled the identification of the particular crystallins, and their exact sites of amino acid modification.
  
  
  METHODS
  Analysis of proteins from cataractous lenses revealed that there are sites on some structural proteins that show a consistently greater degree of deterioration than age-matched normal lenses.
  
  
  CONCLUSIONS
  The most abundant posttranslational modification of aged lens proteins is racemization. Deamidation, truncation and crosslinking, each arising from the spontaneous breakdown of susceptible amino acids within proteins, are also present. Fundamental to an understanding of nuclear cataract etiology, it is proposed that once a certain degree of modification at key sites occurs, that protein-protein interactions are disrupted and lens opacification ensues.
  
  
  CONCLUSIONS
  Since long-lived proteins are now recognized to be present in many other sites of the body, such as the brain, the information gleaned from detailed analyses of degraded proteins from aged lenses will apply more widely to other age-related human diseases. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
authors: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia. Electronic address: rjwt@uow.edu.au.
authors: Roger J W
authors: RJ
authors: Truscott
authors: Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia.
authors: Michael G
authors: MG
authors: Friedrich
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002386:Cataract / Q000209:etiology / Q000378:metabolism*; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008956:Models, Chemical; D011489:Protein Denaturation; D017510:Protein Folding
chemical_list: D003459:Crystallins
keywords: Crystallins; Human aging; Lens; Lifespan; Protein degradation