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. 2006 Jun 22;28(2):209–218. doi: 10.1007/s11357-006-9010-z

Extension of mouse lifespan by overexpression of catalase

Samuel E Schriner 1,✉, Nancy J Linford 2
PMCID: PMC2464724  PMID: 19943142

Abstract

The free radical theory of aging was originally proposed 50 years ago, and is arguably the most popular mechanism explaining the aging process. According to this theory, aging results from the progressive decline in organ function due to the damage generated by reactive oxygen species (ROS). These chemical species are a normal part of metabolism, and a group of enzymes exists to protect cells against their toxic effects. One of these species is hydrogen peroxide (H2O2), which can be degraded by catalase. To determine the role of hydrogen peroxide in aging and its importance in different subcellular compartments, transgenic mice were developed with increased catalase activities localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). The largest effect on lifespan was found in MCAT animals, with a 20% increase in median lifespan and a 10% increase in the maximum lifespan. A more modest effect was seen in PCAT animals, and no significant change was found in NCAT animals. Upon further examination of the MCAT mice, it was found that H2O2 production and H2O2-induced aconitase inactivation were attenuated, oxidative damage and the development of mitochondrial deletions were reduced, and cardiac pathology and cataract development were delayed. These results are consistent with a role of H2O2 in the development of pathology and in the limitation of mouse lifespan. They also demonstrate the importance of mitochondria as a source, and possible target, of ROS.

Key words: aconitase, aging, catalase, hydrogen peroxide, lifespan, mitochondria, mitochondrial DNA, reactive oxygen species, superoxide dismutase

Abbreviations

FRTA

free radical theory of aging

GPX

glutathione peroxidase

MCAT

mitochondrial-targeted catalase

mtDNA

mitochondrial DNA

NCAT

nuclear-targeted catalase

PCAT

peroxisomal (wild-type) catalase

ROS

reactive oxygen species

SOD

superoxide dismutase

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