Extension of murine life span by overexpression of catalase targeted to mitochondria.
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.
Schriner
Samuel E
SE
Department of Genome Sciences, University of Washington, Seattle, WA 91895, USA.
Linford
Nancy J
NJ
Martin
George M
GM
Treuting
Piper
P
Ogburn
Charles E
CE
Emond
Mary
M
Coskun
Pinar E
PE
Ladiges
Warren
W
Wolf
Norman
N
Van Remmen
Holly
H
Wallace
Douglas C
DC
Rabinovitch
Peter S
PS
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
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