Ubiquitous overexpression of CuZn superoxide dismutase does not extendlife span in mice
Abstract
Oxidative damage has been implicated in the aging process and in a number of degenerative diseases. To investigate the role of oxygen radicals in the aging process in mammals, the life spans of transgenic mice on a CD-1 background expressing increased levels of CuZn superoxide dismutase (CuZnSOD), the enzyme that metabolizes superoxide radicals, were determined. Homozygous transgenic mice with a two- to five-fold elevation of CuZnSOD in various tissues showed a slight reduction of life span, whereas hemizygous mice with a 15- to 3-fold increase of CuZnSOD showed no difference in life span from that of the nontransgenic littermate controls. The results suggest that constitutive and ubiquitous overexpression of CuZnSOD alone is not sufficient to extend the life spans of transgenic mice.
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In isolated liver mitochondria, an [O2] >50 μM does not alone result in greater O2•− generation.
“but in isolated liver mitochondria, an [O2] >50 μM does not alone result in greater O2•− generation, as shown in Fig. 20 (161).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [161]
H2O2 generation as a percentage of the respiratory rate increased fourfold (state 4) and sixfold (state 3) from 20 μM to near zero O2.
“It was of interest, however, that H2O2 generation as a percentage of the respiratory rate increased fourfold (state 4) and sixfold (state 3) from 20 μM to near zero [O2].”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [161]
Hypoxia does not itself increase ROS in isolated mitochondria.
“However, this must be reconciled by the finding in isolated mitochondria that hypoxia does not itself increase ROS (Fig. 20) (161).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [161]
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Life span extension and cancer risk: myths and reality
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- Authors
- Huang, T., Carlson, E. J., Gillespie, A. M., Shi, Y., & Epstein, C. J.
- Affiliations
- University of California, San Francisco (US)
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-01-01
- Volume
- 55
- Issue
- 1
- Pages
- B5-B9
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- OpenAlex
- W2134200048
- Cited by
- 216
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 11 · 2013: 10 · 2012: 12
- FWCI
- 3.32
- 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 (AG16998, R01AG016998, AG-08938, P01AG008938)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- Cu/Zn superoxide dismutase, lifespan extension, aging, oxidative stress, superoxide, transgenic mice, ICR mice, antioxidant enzymes, degenerative diseases
- MeSH terms
- Aging, Analysis of Variance, Animals, Longevity, Mice, Transgenic, Superoxide Dismutase, Chi-Square Distribution, Proportional Hazards Models, Free Radical Scavengers, Mice
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