Membrane association of proteins in the aging human lens: profound changes take place in the fifth decade of life.
OBJECTIVE
To characterize age-related changes to proteins in the center of the human lens.


METHODS
Human lenses of different ages were dissected using trephines. Sucrose density gradient centrifugation was used to separate the proteins from two defined nuclear regions. Densitometry of Coomassie-stained protein bands was compared with lipid analysis with the use of mass spectrometry.


RESULTS
A profound change in the density gradient profiles of lenses occurred at approximately age 40. As soluble crystallins decreased, four higher density bands appeared that were absent in younger lenses. These four bands contained crystallins, as well as membrane lipids, and appear to have resulted from the interaction of denatured crystallins with fiber cell membranes.


CONCLUSIONS
Changes in lens proteins and membranes can be detected in each decade of life; however, major changes to the lens crystallins of the nucleus take place between age 40 and 50, after the loss of free soluble alpha crystallin. These alterations are consistent with large-scale binding of crystallin aggregates to fiber cell membranes after middle age.
Friedrich
Michael G
MG
Save Sight Institute, Sydney University, Sydney, NSW, Australia.
Truscott
Roger J W
RJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D002499:Centrifugation, Density Gradient; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins / Q000378:metabolism*; D003720:Densitometry; D005260:Female; D006801:Humans; D007907:Lens Nucleus, Crystalline / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D003459:Crystallins; D008563:Membrane Lipids; D008565:Membrane Proteins