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J Gerontol A Biol Sci Med Sci. 2007 Sep;62(9):932-42.

Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis.

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Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, TX, USA.

Erratum in

  • J Gerontol A Biol Sci Med Sci. 2008 Aug;63(8):776. VanRemmen, Holly [corrected to Van Remmen, Holly].


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 50% in all tissues of Gpx4(+/-) mice. Pathological analysis revealed that Gpx4(+/-) mice showed a delayed occurrence of fatal tumor lymphoma and a reduced severity of glomerulonephritis. Compared to WT mice, Gpx4(+/-) mice showed significantly increased sensitivity to oxidative stress-induced apoptosis. Our data indicate that lifelong reduction in Gpx4 increased life span and reduced/retarded age-related pathology most likely through alterations in sensitivity of tissues to apoptosis.

[Indexed for MEDLINE]

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