Biology of aging brain.
Normal aging of the nervous system is associated with some degree of decline in a number of cognitive functions. With the present day attempts to increase the life span, understanding the metabolic interactions and various mechanisms involved in normal neuronal aging continues to be a challenge. Loss of neurons is now recognized to be more modest than the initial estimates suggested and the loss only affected some of the specific neuroanatomical areas like hippocampus and prefrontal cortex. Individual neurons in addition show reduced size of dendritic and axonal arborization. Neurons have significant homeostatic control of the essential physiological functions like synaptic excitability, gene expression and metabolic regulation. Deviation in these normal events can have severe consequences as observed in aging and neurodegeneration. Based on experimental evidence, the evolution of aging is probably the result of altered metabolic triad: the mitochondria, reactive oxygen species and intracellular calcium homeostasis. Perturbations in the metabolic and functional state of this triad lead to a state of decreased homeostatic reserve, where the aged neurons still could maintain adequate function during normal activity. However, these neurons become vulnerable to the stress of excessive metabolic loads associated with spells of ischemia, trauma progressing to neuronal degeneration. Age-related neuronal dysfunction probably involves a host of subtle changes involving the synapses, receptors, neurotransmitters, cytological alterations, electrical transmission, leading to cognitive dysfunction. An exaggeration of it could be the clinical manifestation of dementia, with intraneuronal accumulation of protein aggregates deranging the metabolic state. This review deals with some of the structural, functional and metabolic features of aging nervous system and discusses briefly the functional consequences.
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore - 560 029, Karnataka, India. shankarsk2004@gmail.com
S K
SK
Shankar
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013569:Synapses / Q000502:physiology
D017382:Reactive Oxygen Species; D002118:Calcium