title: Extension of murine life span by overexpression of catalase targeted to mitochondria.
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.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 91895, USA.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Schriner
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Linford
authors.forename: George M
authors.initials: GM
authors.lastname: Martin
authors.forename: Piper
authors.initials: P
authors.lastname: Treuting
authors.forename: Charles E
authors.initials: CE
authors.lastname: Ogburn
authors.forename: Mary
authors.initials: M
authors.lastname: Emond
authors.forename: Pinar E
authors.initials: PE
authors.lastname: Coskun
authors.forename: Warren
authors.initials: W
authors.lastname: Ladiges
authors.forename: Norman
authors.initials: N
authors.lastname: Wolf
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
authors.forename: Peter S
authors.initials: PS
authors.lastname: Rabinovitch
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000154:Aconitate Hydratase / Q000378:metabolism; D000375:Aging; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002386:Cataract / Q000473:pathology; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D005609:Free Radicals; D006331:Heart Diseases / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008136:Longevity; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020675:Peroxisomes / Q000201:enzymology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D005609:Free Radicals; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase; D003849:Deoxyguanosine