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| NEUROSCIENCE | ARTICLE


certain diseases and cancers. A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base), to a large segment of a chromosome. Gene mutations occur in two ways: they can be


inherited from a parent or acquired during a personÕs lifetime. Mutations that are passed from parent to child are called hereditary mutations, or germline mutations (present in the egg and sperm cells). This type of mutation is present throughout a personÕs life in virtually every cell in the body. Mutations that occur only in an egg or sperm cell, or those that occur just after fertilisation, are called new (de novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell, but has no family history of the disorder. As oxidation for metal or other substances can damage the strength of the core, so too can DNA oxidation damage the cell, creating functional disorders. This leads to a modification of the proteins produced. Protein aggregation is a biological phenomenon in


which mis-folded proteins aggregate (i.e. accumulate and clump together) either intra- or extracellularly3, 4


. These


protein aggregates are often toxic, and have been implicated in a variety of diseases known as amyloidoses, including AlzheimerÕs disease, ParkinsonÕs disease and prion disease5, 6


. Lipid peroxidation refers to the oxidative degradation HO2


of lipids. It is the process in which free radicals ÔstealÕ electrons from the lipids in cell membranes, resulting in cell damage. Initiation is the step in which a fatty acid radical is produced. The most notable initiators in living cells are reactive oxygen species (ROS), such as OHá , which combines with a hydrogen atom to make


and


water and a fatty acid radical. The fatty acid radical is not a stable molecule, so reacts readily with molecular oxygen, thereby creating a peroxyl-fatty acid radical. This is also an unstable species that reacts with another free fatty acid, producing a different fatty acid radical and a


Neuronal


dysfunction is any disorder of the bodyÕs nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms.


lipid peroxide, or a cyclic peroxide if it reacts with itself. This cycle continues, as the new fatty acid radical reacts in the same way.


Dissecting the causes of ageing Energy dysregulation occurs as the result of excessive calorie intake, insulin resistance, oxyradical production and glycation. Both molecular damage and energy dysregulation drive hormesis and adaptation, and neuronal dysfunction and death Hormesis is the term for a generally favourable


biological response to low exposure to toxins and other stressors. A pollutant or toxin showing hormesis thus has the opposite effect in small doses as in large doses. A related concept is mithridatism, which refers to the wilful exposure to toxins in an attempt to develop immunity against them. Neuronal dysfunction is any disorder of the bodyÕs


nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakness, poor coordination, loss of sensation, uncoordinated movements, confusion, dementia, pain and altered levels of consciousness, and lead to synaptic dysfunction, synaptic loss, dendritic regression, apoptosis, impaired neurogenesis, cytokine cascades, microglial activation, impaired detoxification, and demyelination. The ageing process further gives rise to free radical


generation; enhanced mitochondrial inducible nitric oxide (NO) synthase activity with the result of increased NO production, decreased respiratory complex activity, impaired electron transport, with the final opening of the mitochondrial permeability transition pore, driving the main factor of ageing ® mitochondrial dysfunction. These processes work together to cause ageing and are therefore what should be explored when focusing on anti-ageing.


prime-journal.com | June 2012 ❚ 47


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