Mechanisms of Aging in Lens Cells, Relation to Cataract
Norman Wolf, William Pendergrass, Narendra Singh, Philip Penn, and Yi Li.
Dept. of Pathology, Univ. of Washington, Seattle, WA.
Age-related cataract, a major pathology in humans, is also found in
laboratory rodents. The etiology is held, but not completely proven, to be due to
accumulation of oxidative damage to the lens, producing changes in the refractive
internal lens fiber cells, or in the surface lens epithelial cells (LECs) that
protect the interior and later migrate internally to become the lens fibers. LEC
cataractogenesis may be due to either photoxidation or free-radicals of internal
origin. Our studies in mice and rats have shown that with aging the LECs lose
replicative rate in vivo and replicative capacity in vitro, coupled with a
significant in vivo shortening of their telomeres. Further, their resistance to
oxidative damage by hydrogen peroxide in vitro significantly diminishes with age.
All of these age-related deficits, including age-related cataract formation, are
significantly minimized by long term caloric restriction, a regimen that also
extends animal lifespan and lessens the susceptibility to several cellular
insults (oxidative free radicals, heat, toxic chemicals, and inflicted or
spontaneous carcinogenesis). Related to the source of cataractogenesis, LEC
mitochondrial efficiency, a key factor in the production of cellular pump energy
as well as oxidative damage, was found to decrease with age. We conclude that
aging is accompanied by increased LEC sensitivity to oxidative damage, decreased
mitochondrial efficiency, telomere shortening, loss of replicative capacity and
cataract development. As a model system, the lens provides an age-related
pathology,cataract, that correlates with the accretion of cellular changes
intrinsic to the process of aging and testable for causation.
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