The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Reduction in Glutathione Peroxidase 4 Increases Life Span Through Increased Sensitivity to Apoptosis
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.
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“Mice heterozygous for the mitochondrial glutathione peroxidase 4 or the ubiquinone biosynthesis protein CLK1 display high levels of mitochondrial oxidative stress, yet live longer than their wild-type counterparts 93, 94.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [93]
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Cites
Biochemical Pathways of Caspase Activation During Apoptosis
Budihardjo, I. I., Oliver, H., Lutter, M. L., Luo, X., & Wang, X. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.269 · Cited by 2,577
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y. (2003) · Nature · doi:10.1038/nature01298 · Cited by 2,109
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051
Suppression of Aging in Mice by the Hormone Klotho
Kurosu, H., Yamamoto, M., Clark, J. D., Pastor, J. V., Nandi, A., Gurnani, P., McGuinness, O. P., Chikuda, H., Yamaguchi, M., Kawaguchi, H., et al. (2005) · Science · doi:10.1126/science.1112766 · Cited by 1,935
Extension of murine life span by overexpression of catalase targeted to mitochondria
Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) · Science · doi:10.1126/science.1106653 · Cited by 1,724
The p66shc adaptor protein controls oxidative stress response and life span in mammals
Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P. P., Lanfrancone, L., & Pelicci, P. G. (1999) · Nature · doi:10.1038/46311 · Cited by 1,712
Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors
Kagan, V. E., Tyurin, V. A., Jiang, J., Tyurina, Y. Y., Ritov, V. B., Amoscato, A. A., Osipov, A. N., Belikova, N. A., Kapralov, A. A., Kini, V., et al. (2005) · Nature Chemical Biology · doi:10.1038/nchembio727 · Cited by 1,256
Lipid hydroperoxide generation, turnover, and effector action in biological systems
Girotti, A. W. (1998) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32182-9 · Cited by 1,215
Mechanisms of free radical oxidation of unsaturated lipids
Porter, N. A., Caldwell, S. E., & Mills, K. A. (1995) · Lipids · doi:10.1007/bf02536034 · Cited by 1,208
Giorgio, M., Migliaccio, E., Orsini, F., Paolucci, D., Moroni, M., Contursi, C., Pelliccia, G., Luzi, L., Minucci, S., Marcaccio, M., et al. (2005) · Cell · doi:10.1016/j.cell.2005.05.011 · Cited by 1,176
Research works printed but not linked: 6
- 1993, J NUTR SCI VITAMINOL, 39, 575
- Bronson, 1991, Growth, development, and aging : GDA, 55, 169
- 2000, The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 55A, B381
- 2000, 152, 307
- Warner, 1999, Anticancer Research, 19, 2837
- 1989, Aging, 1, 3
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Broadening horizons: the role of ferroptosis in cancer
Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00462-0 · Cited by 3,012
The development of the concept of ferroptosis
Hirschhorn, T., & Stockwell, B. R. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.043 · Cited by 1,052
Oxidative Stress, Mitochondrial Dysfunction, and Aging
Cui, H., Kong, Y., & Zhang, H. (2011) · Journal of Signal Transduction · doi:10.1155/2012/646354 · Cited by 1,076
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
Hamanaka, R. B., & Chandel, N. S. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.002 · Cited by 1,011
Ristow, M., & Zarse, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.014 · Cited by 789
Metadata
- Authors
- Ran, Q., Liang, H., Ikeno, Y., Qi, W., Prolla, T. A., Roberts, L. J., Wolf, N., VanRemmen, H., & Richardson, A.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of Wisconsin–Madison (US)
- Vanderbilt University (US)
- University of Washington (US)
- South Texas Veterans Health Care System (US)
- Corresponding author
- Ran, Q.
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-09-01
- Volume
- 62
- Issue
- 9
- Pages
- 932-942
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- OpenAlex
- W2141897277
- Cited by
- 195
- References
- 64
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 10 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 8 · 2019: 6 · 2018: 14 · 2017: 10 · 2016: 7 · 2015: 12 · 2014: 14 · 2013: 9 · 2012: 12
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P30AG13319, P01 AG19316, P01AG020591, P01AG019316, P30AG013319)
- National Institute of General Medical Sciences (R37 GM42056, R37GM042056)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Keywords
- GPX4, lifespan, aging, apoptosis sensitivity, oxidative stress, lipid peroxidation, antioxidant defense, lymphoma, glomerulonephritis, age-related diseases
- MeSH terms
- Phospholipid Hydroperoxide Glutathione Peroxidase, Aging, Animals, Antioxidants, Glomerulonephritis, Glutathione Peroxidase, Heterozygote, Longevity, Male, Mice, Inbred C57BL, Lipid Peroxidation, Gene Expression, Apoptosis, Mice, Knockout, Oxidative Stress, Mice
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