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PMID: 15879174 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

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

Science (New York, N.Y.) ·Vol. 308 ·No. 5730 ·2005-06-24 ·Pages 1909-11

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.

MeSH Terms

8-Hydroxy-2'-Deoxyguanosine 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

Chemicals

Free Radicals Reactive Oxygen Species 8-Hydroxy-2'-Deoxyguanosine DNA Hydrogen Peroxide Catalase Superoxide Dismutase Aconitate Hydratase Deoxyguanosine

Authors & Affiliations

12 authors, click to expand affiliations / ORCID

Schriner Samuel E

Department of Genome Sciences, University of Washington, Seattle, WA 91895, USA.

Linford Nancy J

Martin George M

Treuting Piper

Ogburn Charles E

Emond Mary

Coskun Pinar E

Ladiges Warren

Wolf Norman

Van Remmen Holly

Wallace Douglas C

Rabinovitch Peter S

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1106653

Published

2005-06-24

Epub

2005-00-05

Pages

1909-11

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NIA NIH HHS · AG001751 · United States

NIA NIH HHS · AG13280 · United States

NIEHS NIH HHS · ES07033 · United States

Corrections

CommentIn

PMID: 15976292

External Links

PubMed source DOI: 10.1126/science.1106653 View journal details

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

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