Neuronal plasticity and stressor toxicity during aging.
Brain aging, Alzheimer disease and stroke share common elements of deficits in calcium regulation, declines in mitochondrial function, increases in generation of reactive oxygen species (ROS), accumulated damage from ROS and immune system dysfunction. The problem is to distinguish less significant side reactions, such as gray hair, from aspects of aging that contribute to disease. Toward establishing cause and effect relationships, a neuron cell culture system is described that allows comparisons with age under uniform environmental conditions. This neuron culture model indicates that susceptibility to death by apoptosis and consequences of the inflammatory response from beta-amyloid are age-related and an inherent characteristic of the neurons. Further mechanistic investigations are possible. New therapeutic approaches are suggested that combine inhibition of calcium overloads (calcium channel blockers), reduced ROS damage (melatonin, N-acetyl-cysteine), and bolstered mitochondrial function and energy generation (creatine). Together with newly demonstrated capabilities for adult and aged neuron regeneration and multiplication, i.e. plasticity, these approaches offer new hope toward reversing age-related decrements and damage from neurodegenerative disease.
Brewer
G J
GJ
Department of Neurology, School of Medicine, Southern Illinois University, Springfield, IL, 62794-9626, USA. gbrewer@siumed.edu
D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D005971:Glutamates; D017382:Reactive Oxygen Species; D002118:Calcium