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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1996-8-19
pubmed:abstractText
The "protease inhibitor model of aging" has been proposed on the basis of observations that young rat brains, livers, and retinas exposed to a protease inhibitor, leupeptin, accumulate lipofuscin-like substances (LLS) that are similar to age pigment, and also display a variety of other manifestations of aging. In order to validate this hypothesis in more general terms, the present study reports attempts to induce age-like changes in kidney cells of young rats. Male F-344 rats (4-5 weeks of age) were continuously infused intraperitoneally (i.p.) with various doses of leupeptin (1-50 mg/100 g/day) for 2 weeks. Control animals received saline solution and normal aged rats (27-30 months-old) received no treatment. Animals were sacrificed and subjected to histological examination. In kidneys of leupeptin-, but not saline-treated rats, generally round-shaped PAS-positive particles were clearly observed, which were predominantly distributed in proximal convoluted tubules, and which resembled particles in normal aged kidneys. With increasing drug doses, particles tended to become bigger and more numerous. The dominant accumulation of LLS in cells of the proximal convoluted tubules had a fine morphologic configuration that resembled age pigments in old rats. Also, there was a concomitant thickening of the basement membrane that was present in leupeptin-treated and aged kidneys, but not in controls. The results, therefore, support the protease inhibitor model of aging and provide an experimental tool for probing the cellular mechanisms of aging.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
786
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Leupeptin causes an accumulation of lipofuscin-like substances and other signs of aging in kidneys of young rats: further evidence for the protease inhibitor model of aging.
pubmed:affiliation
Life Sciences Division, University of Toronto, Scarborough, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't