Abstract:
:The mechanisms that cause aging are not well understood. The oxidative stress hypothesis proposes that the changes associated with aging are a consequence of random oxidative damage to biomolecules. We hypothesized that oxidation of specific proteins is critical in controlling the rate of the aging process. Utilizing an immunochemical probe for oxidatively modified proteins, we show that mitochondrial aconitase, an enzyme in the citric acid cycle, is a specific target during aging of the housefly. The oxidative damage detected immunochemically was paralleled by a loss of catalytic activity of aconitase, an enzyme activity that is critical in energy metabolism. Experimental manipulations which decrease aconitase activity should therefore cause a decrease in life-span. This expected decrease was observed when flies were exposed to hyperoxia, which oxidizes aconitase, and when they were given fluoroacetate, an inhibitor of aconitase. The identification of a specific target of oxidative damage during aging allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process.
journal_name
Proc Natl Acad Sci U S Aauthors
Yan LJ,Levine RL,Sohal RSdoi
10.1073/pnas.94.21.11168subject
Has Abstractpub_date
1997-10-14 00:00:00pages
11168-72issue
21eissn
0027-8424issn
1091-6490journal_volume
94pub_type
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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