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The free radical theory of aging states that organisms age because cells accumulate free radical damage over time. [1] A free radical is any atom or molecule that has a single unpaired electron in an outer shell. [2] While a few free radicals such as melanin are not chemically reactive, most biologically relevant free radicals are highly ...
During ATP production electrons can escape the mitochondrion and react with water, producing reactive oxygen species, ROS for short. ROS can damage macromolecules, including lipids, proteins and DNA, which is thought to facilitate the process of ageing. Electron transport chain in the inner mitochondrial membrane
Reactive oxygen species are implicated in cellular activity to a variety of inflammatory responses including cardiovascular disease. They may also be involved in hearing impairment via cochlear damage induced by elevated sound levels , in ototoxicity of drugs such as cisplatin , and in congenital deafness in both animals and humans.
Mitochondrial ROS can promote cellular senescence and aging phenotypes in the skin of mice. [11] Ordinarily mitochondrial SOD2 protects against mitochondrial ROS. Epidermal cells in mutant mice with a genetic SOD2 deficiency undergo cellular senescence, nuclear DNA damage, and irreversible arrest of proliferation in a portion of their keratinocytes.
Cells can also be induced to senesce by DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes, and cell-cell fusion. Normally, cell senescence is reached through a combination of a variety of factors (i.e., both telomere shortening and oxidative stress). [13]
Reactive oxygen species (ROS) have been discarded as unwanted byproducts of oxidative phosphorylation in mitochondria by the proponents of the free-radical theory of aging promoted by Denham Harman. The free-radical theory states that compounds inactivating ROS would lead to a reduction of oxidative stress and thereby produce an increase in ...
Reactive oxygen species levels increase with age in these mutant strains and show a similar pattern to the pattern of DNA damage increase with age. Thus it appears that superoxide dismutase plays a substantial role in preserving genome integrity during aging in S. cerevisiae. SOD2 knockout or null mutations cause growth inhibition on ...
E. coli cells have revealed similarities to the aging process of higher organisms. The similarities include increased oxidation of cellular constituents and its target specificity, the role of antioxidants and oxygen tension in determining life span, and an apparent trade-off between activities related to reproduction and survival.