The Role Of Oxidative Stress In Ageing: Part 1
Research has shown that oxidative stress can contribute to human ageing. As we age all of our cells will accumulate oxidation products from lipids sugars, proteins and nucleic acids (Jiang et al, 2006). These oxidation products are known as reactive oxygen species (ROS). These are a group of unstable, highly reactive molecules. They include oxygen ions, free radicals, and peroxides.
They are extremely reactive due to having one or more unpaired electron in their outer valence shell (Lee, 2004). Oxidative stress occurs when there is an imbalance between ROS and antioxidants. This can be caused by an antioxidant deficient diet, or an accumulation of ROS (Lee, 2004).
Although reactive oxygen species can be harmful when in present in large quantities they do have an important function in various biological processes. For example nitric oxide plays a crucial role as a signalling molecule in the majority of organs and tissues throughout the body (Fang et al, 2002). Moreover singlet oxygen molecules produced from neutrophils are involved defending the body from tackle infection. When produced they can induce an inflammatory response and destroy pathogenic viruses or bacteria (Stief, 2003). These are just some of the functions reactive oxygen species have; they are also involved in activating transcription factors, switching on gene expression, in addition to a wide variety of signalling tasks (Lee, 2004).
Reactive oxygen species can come from both internal and external sources. The external sources include ultraviolet radiation, ionizing radiation, smoking and various environmental pollutants (Royle, 2007). These environmental sources are very high in energy and when cells within the human body are exposed to these high doses of radiation and pollutants it can cause them to become damaged. As a result these damaged cells may not be able to remove ROS effectively and thus can lead to free radical production and excess ROS production (Spiteller, 2001).
Peroxisomes are one internal source of reactive oxygen species. These organelles are involved in the metabolism of fatty acids. They contain various enzymes; some of which are involved in removing the hydrogen atom from organic substrates and transfer it to a water molecule in the process creating hydrogen peroxide. Hydrogen peroxide is a toxic reactive oxygen species.
Mitochondria expend roughly 90% of the oxygen present in aerobic organisms and thus are the main internal source of reactive oxygen species. Between 1 and 5% of this oxygen is transformed into reactive oxygen species (Lee, 2004). The process that created the most ROS within the mitochondria is the electron transport chain (Royle, 2007). This process takes place on the inner membrane of the mitochondria. The two main sites of ROS production are complexes I (NADH dehydrogenase) and III (ubiquinone-cytochrome c reductase) (Katalin, 2007). These sites reduce the superoxide anion into hydrogen peroxide. In its natural state hydrogen peroxide has an insignificant level of toxicity. But hydrogen peroxide can easily bind to iron and copper ions to produce highly toxic hydroxyl radicals. Because the resultant hydroxyl radical has no charge it can easily pass through the lipid membranes of mitochondria (Grene, 2002). These ROS can have damaging effects on both mtDNA and nuclear DNA
All of these free radicals and reactive oxygen species have been shown to contribute to ageing. When there is an imbalance of ROS and antioxidants, a state of oxidative stress exists. The excess ROS can cause lipid oxidation, protein oxidation, damage to double strand DNA and can alter the expression of various genes (Lee, 2004).
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