Age-dependent denaturation of enzymes in the human lens: a paradigm for organismic aging?
Little is known about the rate of denaturation of proteins within the human body. To monitor this decline, human eye lenses were dissected into discrete regions that were formed at different stages of life and assayed for activity of lactate dehydrogenase (LDH) and a particularly stable enzyme, glutathione reductase (GR). Activity was highest for both enzymes in the most recently synthesized outer part of the lens, decreased further into the lens, and, for LDH, was barely detectable in nuclear regions that consist of proteins that were synthesized in utero. For LDH, 95% of total lens activity was found in the outer half of the adult lens at all ages. Activity was unchanged in the outermost part of the lens as a function of age, suggesting that the ability of humans to synthesize the two enzymes is not impaired, even up to the tenth decade. After age of 40, LDH activity declined steadily in the interior of the lens at the rate of 8.3% per decade. GR activity diminished more slowly, and western blotting indicated that both denaturation of the enzyme and truncation were responsible. These data support the view that few, if any, metabolic pathways remain in the center of older lenses. Exposure of the enzymes to physiological pH and temperature over a period of decades is presumably sufficient to cause denaturation. The center of older human lenses is a unique environment in which the accumulation of untoward posttranslational modifications to proteins can be studied in the absence of significant enzymatic amelioration.
Zhu
Xiangjia
X
Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
Korlimbinis
Anastasia
A
Truscott
Roger J W
RJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D005980:Glutathione Reductase / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D007908:Lens, Crystalline / Q000201:enzymology*; D008875:Middle Aged; D011489:Protein Denaturation; D055815:Young Adult
D007770:L-Lactate Dehydrogenase; D005980:Glutathione Reductase