Extension of murine life span by overexpression of catalase targeted to mitochondria.

Authors: Schriner SE; Linford NJ; Martin GM; Treuting P; Ogburn CE; Emond M; Coskun PE; Ladiges W; Wolf N; Van Remmen H; Wallace DC; Rabinovitch PS

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.

Keywords: Aconitate Hydratase/metabolism; *Aging; Animals; Arteriosclerosis/pathology; Catalase/genetics/*metabolism; Cataract/pathology; Cell Nucleus/enzymology/metabolism; DNA/chemistry; Deoxyguanosine/*analogs & derivatives/analysis; Female; Free Radicals; Heart Diseases/pathology; Humans; Hydrogen Peroxide/*metabolism; *Longevity; Male; Mice; Mice, Transgenic; Mitochondria/enzymology/*metabolism; Mitochondria, Heart/enzymology/*metabolism; Muscle, Skeletal/chemistry; Myocardium/chemistry/pathology; Oxidation-Reduction; Oxidative Stress; Peroxisomes/enzymology; Reactive Oxygen Species/*metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Superoxide Dismutase/genetics/metabolism
Journal: Science (New York, N.Y.)
Volume: 308
Issue: 5730
Pages: 1909-11
Date: May 10, 2005
PMID: 15879174
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Citation:

Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science (New York, N.Y.) 308: 1909-11.


Study Lifespan Factors:
  • CAT catalase


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