Normal brain ageing: models and mechanisms

Abstract

Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria-reactive oxygen species (ROS)-intracellular Ca 2C . The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca 2C homeostasis, ATP production and generation of ROS.

Ageing and the brain

“…This is increased in normal ageing [46]. Ca 2+ imaging studies have shown that the resting Ca 2+ concentration in CA 1 hippocampal neurons does not change with ageing, but that these cells show a greater rise in Ca 2+ in response to stimulation [56].…”

“…Cellular and molecular changes in brain ageing have been well reviewed recently [44][45][46]. Here we consider some of the more important factors.…”

Airways oxidative stress, lung function and cognitive impairment in aging

“…The role of oxygen radicals and ROS in neurodegeneration and cognitive decline has been demonstrated previously [18][19][20]. The age-related increase in oxidative brain damage is well exemplified by products of lipid peroxidation, protein oxidation and oxidative modifications in nuclear and mithocondrial DNA [21].…”

Vulnerability to Seizures Induced by Potassium Dyshomeostasis in the Hippocampus in Aged Rats

“…3) Normal aging is not associated with widespread neuronal loss, but becomes increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischemia or neurodegenerative process. 4) Neurological diseases such as ischemia and dementia increase with aging. In both acute and chronic neurological diseases, glutamate excitotoxicity via excess of extracellular glutamate concentration is involved in neuronal damage.…”