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Mitochondrial oxidative stress plays a key role in aging and apoptosis
J Sastre1, F V Pallardó, J Viña
1Departamento de Fisiología, Facultad de Medicina, Universitat de Valencia, Spain.
Abstract:
Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the age-associated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver.
Insights
Mitochondria accumulate damage over time, contributing to aging. Antioxidants like Ginkgo biloba extract can protect against this mitochondrial damage, potentially slowing the aging process.
Area of Science:
- Gerontology
- Cell Biology
- Biochemistry
Background:
- The mitochondrial theory of aging, proposed in 1972 and 1980, suggests mitochondria act as a biological clock.
- High oxygen consumption in postmitotic cells generates oxygen radicals, potentially exceeding cellular antioxidant defenses and leading to mitochondrial damage.
- Age-related changes include decreased cardiolipin content and increased lipid peroxidation and protein oxidation within mitochondria.
Purpose of the Study:
- To explore the role of mitochondria in cellular aging.
- To investigate the relationship between mitochondrial damage, oxidative stress, and lifespan.
- To evaluate the protective effects of antioxidants against age-associated mitochondrial damage.
Main Methods:
- Review of existing literature on mitochondrial aging and oxidative stress.
- Analysis of studies on cell degeneration induced by aged mitochondria.
- Examination of the impact of antioxidants on mitochondrial DNA (mtDNA) and glutathione oxidation.
Main Results:
- Mitochondrial damage, including mutations in mtDNA and increased reactive oxygen species production, is linked to the aging process.
- An inverse relationship exists between mitochondrial hydroperoxide production and species' maximum lifespan.
- Antioxidants, including sulfur-containing compounds, vitamins C and E, and Ginkgo biloba extract (EGb 761), demonstrate protective effects against mitochondrial oxidative damage.
Conclusions:
- Mitochondria play a crucial role in cellular aging due to accumulated oxidative damage.
- Antioxidant treatments, particularly EGb 761, can mitigate age-associated mitochondrial dysfunction and damage in organs like the brain and liver.