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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.

    Ran Q, Liang H, Ikeno Y, Qi W, Prolla TA, Roberts LJ 2nd, Wolf N, Van Remmen H, Richardson A.

    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.

    PMID: 17895430 [PubMed - indexed for MEDLINE]

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