Normal brain ageing: models and mechanisms.
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 Ca2+. 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 Ca2+ homeostasis, ATP production and generation of ROS.
Toescu
Emil C
EC
Division of Medical Sciences, University of Birmingham Department of Physiology Edgbaston, Birmingham B15 2TT, UK. e.c.toescu@bham.ac.uk
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D002118:Calcium