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

Qitao Ran, Hanyu Liang, Yuji Ikeno, Wenbo Qi, Tomas A. Prolla, L. Jackson Roberts, Norman Wolf, Holly Vanremmen, Arlan Richardson

Research output: Contribution to journalArticle

122 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)932-942
Number of pages11
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume62
Issue number9
DOIs
StatePublished - Sep 2007

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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