Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males
Abstract
We have investigated the differential mitochondrial oxidative stress between males and females to understand the molecular mechanisms enabling females to live longer than males. Mitochondria are a major source of free radicals in cells. Those from female rats generate half the amount of peroxides than those of males. This does not occur in ovariectomized animals. Estrogen replacement therapy prevents the effect of ovariectomy. Mitochondria from females have higher levels of reduced glutathione than those from males. Those from ovariectomized rats have similar levels to males, and estrogen therapy prevents the fall in glutathione levels that occurs in ovariectomized animals. Oxidative damage to mitochondrial DNA in males is 4-fold higher than that in females. This is due to higher expression and activities of Mn-superoxide dismutase and of glutathione peroxidase in females, which behave as double transgenics overexpressing superoxide dismutase and glutathione peroxidase, conferring protection against free-radical-mediated damage in aging. Moreover, 16S rRNA expression, which decreases significantly with aging, is four times higher in mitochondria from females than in those from males of the same chronological age. The facts reported here provide molecular evidence to explain the different life span in males and females.
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Female mitochondria in the heart, liver, and brain have a higher antioxidant capacity and produce less ROS than males.
“For instance, female mitochondria in the heart, liver, and brain have a higher antioxidant capacity and produce less ROS than males (101, 102).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [102]
Estrogen and progesterone contributed to sex differences in cellular respiration and anti-oxidative functions of brain mitochondria in uninjured female rodents.
“Estrogen and progesterone contributed to sex differences in cellular respiration and anti-oxidative functions of brain mitochondria in uninjured female rodents.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [124]
Brain mitochondria of female rodents had lower oxidative stress than those from males, associated with greater expression and activity of antioxidant enzymes.
“brain mitochondria of female rodents had lower oxidative stress than those from males associated with greater expression and activity of antioxidant enzymes.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [124]
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“For instance, female mitochondria in the heart, liver, and brain have a higher antioxidant capacity and produce less ROS than males (101, 102).”
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- Authors
- Borrás, C., Sastre, J., García-Sala, D., Lloret, A., Pallardó, F. V., & Viña, J.
- Affiliations
- Universitat de València (ES)
- Corresponding author
- Viña, José
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 34
- Issue
- 5
- Pages
- 546-552
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2019978470
- Cited by
- 654
- References
- 41
- Citations by year
- 2026: 22 · 2025: 30 · 2024: 40 · 2023: 37 · 2022: 27 · 2021: 33 · 2020: 33 · 2019: 38 · 2018: 25 · 2017: 36 · 2016: 27 · 2015: 25 · 2014: 24 · 2013: 31 · 2012: 25
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- 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
- Keywords
- sex differences, mitochondrial oxidative stress, antioxidant gene expression, mitochondrial DNA damage, ovariectomy, estrogen replacement therapy, reduced glutathione, manganese superoxide dismutase, glutathione peroxidase, 16S rRNA, aging, longevity, free radicals
- MeSH terms
- Animals, Antioxidants, DNA, Mitochondrial, Estrogens, Female, Glutathione, Glutathione Peroxidase, Male, Mitochondria, Liver, Ovariectomy, Oxidation-Reduction, Oxygen, Peroxides, RNA, RNA, Ribosomal, 16S, Superoxide Dismutase, Gene Expression Regulation, Enzymologic, Rats, Wistar, Reactive Oxygen Species, DNA Primers, Oxidative Stress, Reverse Transcriptase Polymerase Chain Reaction, Rats
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