2007
DOI: 10.1093/gerona/62.9.932
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Abstract: Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme that plays an important role in detoxification of oxidative damage to membrane lipids. Because oxidative stress is proposed to play a causal role in aging, we compared the life spans of Gpx4 heterozygous knockout mice (Gpx4(+/-) mice) and wild-type mice (WT mice). To our surprise, the median life span of Gpx4(+/-) mice (1029 days) was significantly longer than that of WT mice (963 days) even though the expression of Gpx4 was reduced approximately… Show more

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Cited by 155 publications
(116 citation statements)
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“…Similarly, transgenic animal models overexpressing RONS protective enzymes including SOD1 Tg ,26 SOD2 Tg ,24 MSRA Tg ,258 mice overexpressing human CAT in nuclei (nCAT Tg )259 and peroxisomal targeted CAT (pCAT Tg ) (the natural site of CAT)260 have failed to provide evidence of increased lifespan, indicating that RONS are not the fundamental determinants of lifespan. However, GPX4 +/− ,261 TRX1 Tg 262 and the mitochondrial CAT overexpressing (mCAT Tg ) mouse model263 showed ~7%, ~14% and ~21% increases in lifespan, respectively, which may provide support for the theory of oxidative damage in ageing.…”
Section: Non‐enzymatic Key Antioxidants That Contribute To the Maintementioning
confidence: 84%
“…Similarly, transgenic animal models overexpressing RONS protective enzymes including SOD1 Tg ,26 SOD2 Tg ,24 MSRA Tg ,258 mice overexpressing human CAT in nuclei (nCAT Tg )259 and peroxisomal targeted CAT (pCAT Tg ) (the natural site of CAT)260 have failed to provide evidence of increased lifespan, indicating that RONS are not the fundamental determinants of lifespan. However, GPX4 +/− ,261 TRX1 Tg 262 and the mitochondrial CAT overexpressing (mCAT Tg ) mouse model263 showed ~7%, ~14% and ~21% increases in lifespan, respectively, which may provide support for the theory of oxidative damage in ageing.…”
Section: Non‐enzymatic Key Antioxidants That Contribute To the Maintementioning
confidence: 84%
“…Yet, we believe that the increased lifespan recently demonstrated for mice with partial inactivation of GPx4 represent an even greater challenge. Indeed mice heterozygous for GPx4, the gene encoding the only mitochondrial enzymatic antioxidant that directly reduces membranebound lipid hydroperoxides, have an increased median lifespan despite higher levels of biomarkers of oxidative damage [49]. Interestingly, it was recently shown that inactivation of the crucial mitochondrial antioxidant Sod2 increases oxidative damage to proteins and general sensitivity to oxidative stress in C. elegans, yet simultaneously prolongs lifespan of these animals [50].…”
Section: From Incompatible To Irreconcilablementioning
confidence: 99%
“…In worms, insulin/IGF mutants have an increase in free-radical resistance (Gredilla et al 2001;Honda and Honda 1999). Although free radicals have been correlated with senescence, in both mice and worms, there is increasing evidence that they may not be the causative agent (Doonan et al 2008;Ran et al 2007;Van Raamsdonk and Hekimi 2009;Van Remmen et al 2003;Yen et al 2009). The target of rapamycin pathway, which may also link DR and insulin/IGF signaling, regulates autophagy, and this is important for both DR and insulin/IGF mediated longevity (Hansen et al 2008;Kaeberlein et al 2005;Kapahi et al 2004;Melendez et al 2003).…”
Section: Gompertz Analysismentioning
confidence: 99%