5.2.1 Free radicals and ageing
Free radicals are physical species (i.e. molecules or ions) that have unpaired electrons, which makes them very reactive and so damaging to cells. Other non-radical oxygen-based groups such as hydrogen peroxide (H2O2) also cause damage and are involved in the generation of free radicals; together, free radicals and these radical-generating molecules are known as ‘reactive oxygen species’ (ROS). Free radicals and other ROS can cause oxidative damage to DNA, proteins and membrane lipids, thereby altering their structure, and disrupting their functions. This damage provides a constant challenge to eukaryotic cells. Organisms have evolved a variety of biochemical pathways to ‘combat’ ROS. Among these defences are small molecules, such as vitamin C, that ‘scavenge’ free radicals, and enzymes that convert them to harmless products (an example is superoxide dismutase or SOD). However, if the balance between the generation of ROS and the cell's defences is shifted or disrupted in some way, a situation known as ‘oxidative stress’ arises. Evidence from a number of experimental systems shows that oxidative stress can lead to pathologies such as cellular transformation to malignancy, cardiovascular disease, immune system dysfunction, neurodegenerative disorders and enhanced ageing. Oxidative stress is thought to be a contributing factor to the decline in both cognitive and motor performance seen in ageing. The brain may be particularly vulnerable to the deleterious effects of oxidative damage, because:
it utilises large amounts of oxygen
it contains high concentrations of fatty acids, which readily react with oxygen to produce free radicals known as lipid peroxides
it has little regenerative capacity.