“The brain is particularly vulnerable to free radical damage with its high content of unsaturated fatty acids, high oxygen metabolism (20% of total body consumption) and relatively low levels of endogenous antioxidants. Accumulation of oxidative damage in post-mitotic neurons is a crucial factor in normal brain aging, and contributes directly to cognitive, motor and sensory impairments.”


“Mitochondrial dysfunction and oxidative metabolism are principal sources of oxidative stress leading to neurodegeneration, although NAD(P)H oxidase and other sources of free radicals also contribute.

Neurons have high energy demands (ATP consumption) associated with membrane ionic pumps, channel activity, and synaptic transmission, which can lead to increased free radical production. Elevation in free radicals can increase levels of glutathione disulfide (GSSG) which inhibits the thiol-dependent enzyme NADH dehydrogenase, causing a mitochondrial complex I defect. Mitochondrial dysfunction can lead to neuronal degeneration via impaired production of ATP (through disruption of the electron transport chain (ETC)), increased generation of reactive oxygen species (ROS), altered calcium homeostasis and excitotoxicity. Brains of aged animals have significantly higher levels of oxidized proteins and lipids, and reduced protease activities compared to young animals.


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