| Extension of mouse lifespan by overexpression of catalase. | |
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MedLine Citation:
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PMID: 19943142 Owner: NLM Status: PubMed-not-MEDLINE |
Abstract/OtherAbstract:
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The free radical theory of aging was originally proposed 50 years ago, and is arguably the most popular mechanism explaining the aging process. According to this theory, aging results from the progressive decline in organ function due to the damage generated by reactive oxygen species (ROS). These chemical species are a normal part of metabolism, and a group of enzymes exists to protect cells against their toxic effects. One of these species is hydrogen peroxide (H(2)O(2)), which can be degraded by catalase. To determine the role of hydrogen peroxide in aging and its importance in different subcellular compartments, transgenic mice were developed with increased catalase activities localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). The largest effect on lifespan was found in MCAT animals, with a 20% increase in median lifespan and a 10% increase in the maximum lifespan. A more modest effect was seen in PCAT animals, and no significant change was found in NCAT animals. Upon further examination of the MCAT mice, it was found that H(2)O(2) production and H(2)O(2)-induced aconitase inactivation were attenuated, oxidative damage and the development of mitochondrial deletions were reduced, and cardiac pathology and cataract development were delayed. These results are consistent with a role of H(2)O(2) in the development of pathology and in the limitation of mouse lifespan. They also demonstrate the importance of mitochondria as a source, and possible target, of ROS. |
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Authors:
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Samuel E Schriner; Nancy J Linford |
Publication Detail:
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Type: Journal Article Date: 2006-06-22 |
Journal Detail:
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Title: Age (Dordrecht, Netherlands) Volume: 28 ISSN: 1574-4647 ISO Abbreviation: Age (Dordr) Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2009-11-27 Completed Date: 2009-12-14 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 101250497 Medline TA: Age (Dordr) Country: Netherlands |
Other Details:
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Languages: eng Pagination: 209-18 Citation Subset: - |
Affiliation:
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Center for Molecular and Mitochondrial Medicine and Genetics, Department of Biological Chemistry, University of California, Irvine, 2101 Hewitt Hall, Irvine, CA 92697-3940, USA. schriner@uci.edu |
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