Abstract
To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria (MCAT). Median and maximum life spans were maximally increased (averages of 5 months and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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8-Hydroxy-2'-Deoxyguanosine
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Aconitate Hydratase / metabolism
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Aging*
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Animals
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Arteriosclerosis / pathology
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Catalase / genetics
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Catalase / metabolism*
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Cataract / pathology
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Cell Nucleus / enzymology
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Cell Nucleus / metabolism
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DNA / chemistry
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Deoxyguanosine / analogs & derivatives*
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Deoxyguanosine / analysis
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Female
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Free Radicals
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Heart Diseases / pathology
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Humans
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Hydrogen Peroxide / metabolism*
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Longevity*
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Male
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Mice
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Mice, Transgenic
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Mitochondria / enzymology
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Mitochondria / metabolism*
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Mitochondria, Heart / enzymology
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Mitochondria, Heart / metabolism*
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Muscle, Skeletal / chemistry
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Myocardium / chemistry
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Myocardium / pathology
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Oxidation-Reduction
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Oxidative Stress
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Peroxisomes / enzymology
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Reactive Oxygen Species / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
Substances
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Free Radicals
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Reactive Oxygen Species
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8-Hydroxy-2'-Deoxyguanosine
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DNA
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Hydrogen Peroxide
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Catalase
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Superoxide Dismutase
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Aconitate Hydratase
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Deoxyguanosine